Search results for: Wistar Albinos rats

Authors: Subrat Kumar Bhattamisra, Vivian Lee Yean Yan, Chin Koh Lee, Chew Hui Kuean, Yun Khoon Liew, Mayuren Candasamy

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Geraniol, an acyclic monoterpenoid is the main active constituent in the essential oils of rose and palmorosa. Antioxidant, antibacterial, anticancer and antiulcer activity of geraniol was reported by many researchers. The present investigation was designed to study in vivo antiulcer and anti-Helicobacter pylori activity of geraniol. Antiulcer and anti-H. pylori activity of geraniol was evaluated on acetic acid plus H. pylori induced ulcer in rats. Acetic acid (0.03 mL) was injected to the sub-serosal layer of the stomach through laparotomy under anaesthesia. Orogastric inoculation of H. pylori (ATCC 43504) was done twice daily for 7 days. Geraniol (15 and 30 mg/kg), vehicle and standard drugs (Amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg & omeprazole, 20 mg/kg) was administered twice daily for 14 days. Antiulcer activity of geraniol was examined by the determination of gastric ulcer index, measuring the volume of gastric juice, pH and total acidity, myeloperoxidase activity and histopathological examination. Histopathological investigation for the presence of inflammation, white blood cell infiltration, edema, the mucosal damage was studied. The presence of H. pylori was detected by placing a biopsy sample from antral part of the stomach into rapid urease test. Ulcer index in H. pylori inoculated control group was 4.13 ± 0.85 and was significantly (P < 0.05) lowered in geraniol (30 mg/kg) and reference drug treated group. Geraniol increase the pH of the gastric juice (2.18 ± 0.13 in control vs. 4.14 ± 0.57 in geraniol 30mg/kg) and lower total acidity significantly (P < 0.01) in geraniol (15 & 30 mg/kg). Myeloperoxidase (MPO) activity was measured in stomach homogenate of all the groups. H. pylori control group has significant (P < 0.05) increase in MPO activity compared to normal control group. Geraniol (30 mg/kg) was showed significant (P < 0.05) and most effective among all the groups. Histopathological examination of rat stomach was scored and the total score for H. pylori control group was 8. After geraniol (30 mg/kg) and reference drug treatment, the histopathological score was significantly decreased and it was observed to be 3.5 and 2.0 respectively. Percentage inhibition of H. pylori infection in geraniol (30 mg/kg) and reference drug were found to be 40% and 50% respectively whereas, 100% infection in H. pylori control group was observed. Geraniol exhibited significant antiulcer and anti- H. pylori activity in the rats. Thus, geraniol has the potential for the further development as an effective medication in treating H. pylori associated ulcer.

Keywords: geraniol, helicobacter pylori atcc 43504, myeloperoxidase, ulcer

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Authors: Orish E. Orisakwe, Chinna N. Orish, Anthonet N. Ezejiofor

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African mesquite has been recognized for its antimicrobial, anti-inflammatory, and potential anticarcinogenic activities. However, its neuroprotective benefits against heavy metal-induced neurotoxicity remain largely unexplored. Therefore, the objective of this study was to investigate the neuroprotective properties of African mesquite in the hippocampus and olfactory bulb against common environmental pollutants, including Cd, As, Hg, and Pb. Thirty-five albino Sprague Dawley rats were divided into five groups for the experiment. Group 1 served as the control and did not receive either the heavy metal mixture (HMM) or African mesquite. Group 2 was orally administered HMM, consisting of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 960 days. Meanwhile, groups 3, 4, and 5 were treated with HMM along with African mesquite at doses of 500 mg/kg, 1000 mg/kg, and 1500 mg/kg, respectively. African mesquite reduced heavy metal accumulation in the hippocampus and olfactory bulb. Additionally, Sprague Dawley rats exhibited improved performance in the Passive avoidance and Cincinnati Maze tests. Furthermore, treatment with African mesquite significantly alleviated inflammation macromolecules peroxidation. It also restored the concentrations of SOD, CAT, GSH, GPx, Hmox-1, and reduced the activity of AChE, NRF2 and NFkB and improved histopathological findings. African mesquite exhibits a multifaceted neuroprotective effect with the potential to mitigate various aspects of heavy metal-induced neurotoxicity.

Keywords: African mesquite, heavy metal mixture;, neurotoxicity;, chemoprevention

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Authors: Hanen Bouaziz, Françoise Croute, Najiba Zeghal

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In order to investigate the toxic effects of fluoride on cerebrum maturity of suckling mice, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances, the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and catalase and the level of glutathione decreased significantly in cerebellum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase activity in cerebellum was inhibited after treatment with fluoride. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study, we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.

Keywords: acetylcholinesterase activity, cerebellum, laminin, oxidative stress, suckling mice

Procedia PDF Downloads 373

Authors: Nazmul Huda, Ashik Mosaddik, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi

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Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl₄) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl₄ 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl₄ 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl₄ 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Keywords: polyherbal formulation, sharbat deenar, carbon tetrachloride, silymarin, hepatoprotective

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Authors: Hoda Mahgoub, Abeer Hanafy

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Linagliptin (LNG) belongs to dipeptidyl-peptidase-4 (DPP-4) inhibitor class. DPP-4 inhibitors represent a new therapeutic approach for the treatment of type 2 diabetes in adults. The aim of this work was to develop and validate an accurate and reproducible HPLC method for the determination of LNG with high sensitivity in rat plasma. The method involved separation of both LNG and pindolol (internal standard) at ambient temperature on a Zorbax Eclipse XDB C18 column and a mobile phase composed of 75% methanol: 25% formic acid 0.1% pH 4.1 at a flow rate of 1.0 mL.min-1. UV detection was performed at 254nm. The method was validated in compliance with ICH guidelines and found to be linear in the range of 5–1000ng.mL-1. The limit of quantification (LOQ) was found to be 5ng.mL-1 based on 100µL of plasma. The variations for intra- and inter-assay precision were less than 10%, and the accuracy values were ranged between 93.3% and 102.5%. The extraction recovery (R%) was more than 83%. The method involved a single extraction step of a very small plasma volume (100µL). The assay was successfully applied to an in-vivo pharmacokinetic study of LNG in rats that were administered a single oral dose of 10mg.kg-1 LNG. The maximum concentration (Cmax) was found to be 927.5 ± 23.9ng.mL-1. The area under the plasma concentration-time curve (AUC0-72) was 18285.02 ± 605.76h.ng.mL-1. In conclusion, the good accuracy and low LOQ of the bioanalytical HPLC method were suitable for monitoring the full pharmacokinetic profile of LNG in rats. The main advantages of the method were the sensitivity, small sample volume, single-step extraction procedure and the short time of analysis.

Keywords: HPLC, linagliptin, pharmacokinetic study, rat plasma

Procedia PDF Downloads 223

Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

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Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

Procedia PDF Downloads 246

Authors: Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Amornnat Thuppia, Nuntiya Somparn

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Several dietary and herbal plants have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Ocimum americanum (OA), commonly known as American basil or 'hoary basil', in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 100, 200 and 400 mg/kg for 28 days. Phytochemical screening of plant extracts revealed the presence of alkaloid, cardiac glycosides, tannin and steroid compounds. The extract contained phenolic compounds 36.91 ± 0.66 mg of gallic acid equivalents per gram OA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 41.27 ± 1.86 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. The protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased compared with normal control. Consistent with the induction of γ-GCL protein expression significantly reduction of serum oxidative stress marker malondialdehyde (MDA) was found in rat treated with OA extract compared with control. Taken together, this study provides evidence that Ocimum americanum exhibits direct antioxidant properties and can induce cytoprotective enzyme in vivo.

Keywords: antioxidant, γ-glutamylcysteine ligase, MDA, Ocimum americanum

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Authors: Chirag Raval, Jimmy Toussaint, Tieuvi Nguyen, Hadi Fadaifard, George Wolberg, Steven Quarfordt, Kung-ming Jan, David S. Rumschitzki

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Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.

Keywords: acute hypertension, aquaporin-1, hydraulic conductivity, hydrostatic pressure, aortic endothelial cells, transcellular flow

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Authors: Sizhu Wang, Cuisong Tang, Lin Zhang, Guangyu Tang

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Objective: We aimed to detect the composition of bone marrow fatty acids early after ovariectomized (OVX) surgery and explore the potential mechanism. Methods: Thirty-two female Sprague-Dawley (SD) rats (12 weeks) were randomly divided into OVX group and Sham group (N=16/group), and received ovariectomy or sham surgery respectively. After 3 and 28 days, eight rats in each group were sacrificed to detect the composition of bone marrow fatty acids by gas chromatography–mass spectrometry (GC–MS) and evaluate the trabecular bone microarchitecture by micro-CT. Significant different fatty acids in the early stage of post-menopausal osteoporosis were selected by OPLS-DA and t test. Then selected fatty acids were further studied in the process of osteogenic differentiation through RT-PCR and Alizarin Red S staining. Results: An apparent sample clustering and group separation were observed between OVX group and sham group three days after surgery, which suggested the role of bone marrow fatty acids in the early stage of postmenopausal osteoporosis. Specifically, myristate, palmitoleate and arachidonate were found to play an important role in classification between OVX group and sham group. We further investigated the effect of palmitoleate and arachidonate on osteogenic differentiation and found that palmitoleate promoted the osteogenic differentiation of MC3T3-E1 cells while arachidonate inhibited this process. Conclusion: Profound bone marrow fatty acids changes have taken place in the early stage of post-menopausal osteoporosis. Bone marrow fatty acids may begin to affect osteogenic differentiation shortly after deficiency of estrogen.

Keywords: bone marrow fatty acids, GC-MS, osteoblast, osteoporosis, post-menopausal

Procedia PDF Downloads 75

Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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Authors: Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Zobov, Vladimir Reznik

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Among hepatic pyrimidine used as a means of stimulating protein synthesis and recovery of liver cells in her damaged toxic and infectious etiology. When an experimental toxic hepatitis hepatoprotective activity detected some pyrimidine derivatives. There are literature data on oksimetiluratcila hepatoprotective effect. For analogs of pyrimidine nucleobases - drugs Methyluracilum pentoxy and hepatoprotective effect of weakly expressed. According to the American scientists broad spectrum of biological activity, including hepatoprotective properties, have a 2,4-dioxo-5-arilidenimino uracils. Influenced Xymedon medicinal preparation (1- (beta-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-oksopirimidin) developed as a means of stimulating the regeneration of tissue revealed increased activity of microsomal oxidases human liver. In studies on the model of toxic liver damage in rats have shown hepatoprotective effect xymedon and stimulating its impact on the recovery of the liver tissue. Hepatoprotective properties of the new compound in the series of pyrimidine derivatives L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropirimidine-2-one synthesized on the basis Xymedon preparation were firstly investigated on rats under the carbon tetrachloride action. It was shown the differences of biochemical parameters from the reference value and severity of structural-morphological liver violations decreased in comparison with control group under the influence of the compound injected before exposure carbon tetrachloride. Hepatoprotective properties of the investigated compound were more pronounced in comparison with Xymedon.

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Izuddin Fahmy Abu, Mohamad Haiqal Nizar Mohamad, Muhammad Fattah Fazel, Renu Agarwal, Igor Iezhitsa, Nor Salmah Bakar, Henrik Franzyk, Ian Mellor

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Glaucoma is the global leading cause of irreversible blindness. Currently, the available treatment strategy only involves lowering intraocular pressure (IOP); however, the condition often progresses despite lowered or normal IOP in some patients. N-methyl-D-aspartate receptor (NMDAR) excitotoxicity often occurs in neurodegeneration-related glaucoma; thus it is a relevant target to develop a therapy based on neuroprotection approach. This study investigated the effects of Philanthotoxin-343 (PhTX-343), an NMDAR antagonist, on the neuroprotection of NMDA-induced glaucoma to alleviate visual impairments. Male Sprague-Dawley rats were equally divided: Groups 1 (control) and 2 (glaucoma) were intravitreally injected with phosphate buffer saline (PBS) and NMDA (160nM), respectively, while group 3 was pre-treated with PhTX-343 (160nM) 24 hours prior to NMDA injection. Seven days post-treatments, rats were subjected to visual behavior assessments and subsequently euthanized to harvest their retina and optic nerve tissues for histological analysis and determination of nitrosative stress level using 3-nitrotyrosine ELISA. Visual behavior assessments via open field, object, and color recognition tests demonstrated poor visual performance in glaucoma rats indicated by high exploratory behavior. PhTX-343 pre-treatment appeared to preserve visual abilities as all test results were significantly improved (p < 0.05). H&E staining of the retina showed a marked reduction of ganglion cell layer thickness in the glaucoma group; in contrast, PhTX-343 significantly increased the number by 1.28-folds (p < 0.05). PhTX-343 also increased the number of cell nuclei/100μm2 within inner retina by 1.82-folds compared to the glaucoma group (p < 0.05). Toluidine blue staining of optic nerve tissues showed that PhTX-343 reduced the degeneration changes compared to the glaucoma group which exhibited vacuolation overall sections. PhTX-343 also decreased retinal 3- nitrotyrosine concentration by 1.74-folds compared to the glaucoma group (p < 0.05). All results in PhTX-343 group were comparable to control (p > 0.05). We conclude that PhTX-343 protects against NMDA-induced changes and visual impairments in the rat model by reducing nitrosative stress levels.

Keywords: excitotoxicity, glaucoma, nitrosative stress , NMDA receptor , N-methyl-D-aspartate , philanthotoxin, visual behaviour

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

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Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

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Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

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The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

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Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

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In view of the peculiar environment of the Niger Delta, access to modern health care is limited, hence the inhabitants especially those in the swampy areas resorts to sourcing for alternatives cure for their ailments using plants commonly found in this area without scientific evaluation. Rhizophora racemosa, G. F. Meyer (Rhizophoraceae) is the most abundant mangrove plant in the Niger Delta Area of Nigeria. The plant has been observed to be used for relief of a toothache and dysmenorrhoea among some Ijaw communities in the region. This work has revealed the likely potential of the plant in drug discovery and development. The crude methanol extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) were tested for analgesic effect using fresh egg albumin induced inflammatory pain and Randall–Sellito method to assess the pain threshold. The anti-inflammatory effect was also evaluated with the extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) using acute inflammatory model; fresh egg albumin induced paw oedema and assessed using Plethysmometer in rats. The methanol extracts 300 mg/kg and 600 mg/kg exhibited a significant (P < 0.001) and dose-dependent analgesic activity compared with the negative control and a standard drug diclofenac using ANOVA with Least Significant Difference post hoc test as evidenced by increased pain threshold. Also, the extract significantly (P < 0.001) reduced the rat paw oedema induced by the sub plantar injection of fresh egg albumin when compared with the negative control and a standard diclofenac using above statistical methods. This study revealed that the plant possesses analgesic and anti-inflammatory activities hence provide scientific bases for use as medicine.

Keywords: analgesic, anti-inflammatory, plethysmometer, Rhizophora racemosa

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Authors: Pardis Abolghasemi, Benyamin Hatamsaz

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Background: Diabetic nephropathy is a serious health problem described by specific kidney structure and functional disturbance. Renoprotective effects of the stem cells secretase have been shown in many kidney diseases. The aim is to evaluate the capability of human Wharton’s jelly mesenchymal stem cells conditioned media (hWJMSCs-CM) to alleviate DN in streptozotocin (STZ)-induced diabetes. Methods: Diabetic nephropathy was induced by injection of STZ (60 mg/kg, IP) in twenty rats. Conditioned media was extracted from hWJMSCs at third passages. At week 8, diabetic rats were divided into two groups: treated (hWJMSCs-CM, 500 μl/rat for three weeks, IP) and not treated (DN). In the 11th week, three groups (control, DN and DN+hWJMSCs-CM) were kept in metabolic cages and urine was collected for 24h. Blood pressure (BP) and heart rate (HR) were continuously recorded. The serum samples were maintained for measuring BUN, Cr and angiotensin-converting enzyme (ACE) activity. The left kidney was kept at -80°C for ACE activity assessment. The right kidney and pancreas were used for histopathologic evaluation. Result: Diabetic nephropathy was detected by microalbuminuria and increased albumin/creatinine ratio, as well as the pancreas and renal structural disturbance. Glomerular filtration rate, BP and HR increased in the DN group. The ACE activity was elevated in the serum and kidneys of the DN group. Administration of hWJMSCs-CM modulated the renal functional and structural disturbance and decreased the ACE activity. Conclusion: Conditioned media was extracted from hWJMSCs may have a Renoprotective effect in diabetic nephropathy. This may happen through regulation of ACE activity and renin-angiotensin system inhibition.

Keywords: diabetic nephropathy, mesenchymal stem cells, immunomodulation, anti-inflammation

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Authors: Azza A. Ali, Toqa M. Elnahhas, Abeer I. Abd El-Fattah, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Environmental pollution with the different aluminium (Al) containing compounds especially those in industrial waste water exposes people to higher than normal levels of Al that represents an environmental risk factor. Cosmetics, Al ware, and containers are also sources of Al besides some foods and food additives. In addition to its known neurotoxicity, Al affects other body structures like skeletal system, blood cells, liver and kidney. Accumulation of Al in kidney and liver induces nephrotoxicity and hepatotoxicity. Coenzyme Q10 (CoQ10) is a pseudo-vitamin substance primarily present in the mitochondria. It is a powerful antioxidant and acts as radical scavenger. Wheat grass is a natural product that contains carbohydrates, proteins, vitamins, minerals, enzymes and has antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Cocoa is an excellent source of iron, potent antioxidants and can protect against many diseases. Vinpocetine is an antioxidant and anti inflammatory while zinc is an essential trace element involved in cell division and its deficiency is observed in many types of liver disease. Objective: To evaluate and compare the potency of different drugs (CoQ10, wheatgrass, cocoa, vinpocetine and zinc) against nephro- and hepato-toxicity induced by Al in rats. Methods: Rats were divided to seven groups and received daily for three weeks either saline for control group or AlCl3 (70 mg/kg, IP) for Al-toxicity model groups. Five groups of Al-toxicity model (treated groups) were orally received together with Al each of the following; CoQ10 (200mg/kg), wheat grass (100mg/kg), cocoa powder (24mg/kg), vinpocetine (20mg/kg) or zinc (32mg/kg). Biochemical changes in the serum level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea were measured. Liver and kidney specimens from all groups were also collected for the assessment of hepatic and nephrotic level of inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3, oxidative parameters (MDA, SOD, TAC, NO) and DNA fragmentation. Histopathological changes in liver and kidney were also evaluated. Results: Three weeks of AlCl3 (70 mg/kg, IP) exposure induced nephro- and hepato-toxicity in rats. Treatment by the all used drugs showed protection against hazards of AlCl3. The protective effects were indicated by the significant decrease in ALT, AST, ALP, LDH as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels which were increased by Al. Liver and kidney of the treated groups showed decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation which were increased by Al, together with significant increase in total proteins, SOD and TAC which were decreased by Al. The protection against both nephro- and hepato-toxicity was more pronounced especially with CoQ10 and wheat grass than the other used drugs. Histopathological examinations confirmed the biochemical results of toxicity and of protection. Conclusion: Protection from nephrotoxicity, hepatotoxicity and the consequent degenerations induced by Al can be achieved by using different drugs as CoQ10, wheatgrass, cocoa, vinpocetine and zinc, but CoQ10 as well as wheat grass possesses the most superior protection.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, coenzyme Q10, wheatgrass, cocoa, vinpocetine, zinc

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Authors: Sabrina Barsky, Ashley Monks

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In humans, exercise improves symptoms of various pathological states, although exercise adaptations seem to differ in response to sex. Skeletal muscle anabolism is thought to be regulated by androgen receptor (AR) through poorly specified mechanisms. Interactions of AR and exercise on muscle phenotype remain inconclusive in males, and undetermined in females. We hypothesized that sex differences in exercise adaptations are regulated by the androgenic system and the type of exercise performed. Here we examined interactions between a muscle-specific AR overexpression transgene (HSA-AR) and forced aerobic exercise paradigm on muscle and adipose exercise adaptation in male and female rats. We used dual-energy X-ray absorptiometry (DXA) to examine body composition adaptations post 9-week exercise protocol. We replicated the effects of HSA-AR on body composition, with males only having increased % lean mass and reduced % fat mass (P<0.05). Aerobic exercise improved lean body phenotype significantly, with lesser indices of total and % fat mass (P<0.01) in both sexes. Sex-specific effects of exercise included decreased total body mass (P<0.01) in males and increased lean mass % (P<0.001) in females. Surprisingly, neither AR manipulation nor exercise affected bone parameters in either sex. This varied response in total mass and lean mass according to exercise presents a sexually dimorphic response to exercise. Neither sex showed an interaction between HSA-AR and forced aerobic exercise on body composition. Future work is proposed to examine the effects of exercise type (aerobic versus resistance) and the role of gonadal androgens in sexually dimorphic exercise-mediated mitochondrial adaptations. This work implicates the development of sex-specific exercise therapies.

Keywords: androgen receptor, forced exercise, muscle physiology, sexual dimorphism

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Authors: Nadeem Munawar, David Galbraith, Tariq Mahmood

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Rodenticides are often included as part of an integrated pest management approach for managing rodent species since they are relatively quick and inexpensive to apply. The current field study was conducted to evaluate the effectiveness of formulated baits of zinc phosphide (2%) and the second generation anticoagulant brodifacoum (0.005%) against field rats inhabiting a wheat-groundnut cropping system. Burrow baiting was initiated at the early flowering stages of the respective crops, and continued through three growth stages (tillering / peg formation, flowering, and maturity). Three treatments were done at equal time intervals, with the final baiting being about 2 weeks before harvest. Treatment efficacy of the trials was assessed through counts of active rodent burrows before and after treatments at the three growth stages of these crops. The results indicated variable degrees of reduction in burrow activities following the three bait applications. The reductions in rodent activity in wheat were: 88.8% (at tillering), 92%, (at flowering/grain formation), and 95.5% (at maturity). In groundnut, the rodent activities were reduced by 91.8%, 93.5% and 95.8% at sowing, peg formation, and maturity stages, respectively. The estimated mortality at all three growth stages of both wheat and groundnut ranged between 60-85%. We recommend that a field efficacy study should be conducted with zinc phosphide and brodifacoum bait formulations to determine their field performance in the reduction of agricultural damage by rodent pest species. It is a promising alternative approach for use of the most potent second-generation anticoagulant (brodifacoum) in resistance management, particularly with respect to reducing environmental risks and secondary poisoning.

Keywords: brodifacoum, burrow baiting, second-generation anticoagulant, synergistic effect

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: Nadeem Munawar, Tariq Mahmood, Paula Rivadeneira, Ali Akhter

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In this paper, we review on rodent species which are common inhabitants of agricultural landscapes where they are an important prey source for a wide variety of avian, reptilian, and mammalian predators. Agricultural fields are surrounded by fallow land, which provide suitable sites for shelter and breeding for rodents, while shrubs, grasses, annual weeds and forbs may provide supplementary food. The assemblage of rodent’s fauna in the cropland habitats including cropped fields, meadows and adjacent field structures like hedgerows, woodland and field margins fluctuates seasonally. The mature agricultural crops provides good source of food and shelter to the rodents and these factors along with favorable climatic factors/season facilitate breeding activities of these rodent species. Changes in vegetation height and vegetative cover affect two important aspects of a rodent’s life: food and shelter. In addition, during non-crop period vegetation can be important for building nests above or below ground and it provides thermal protection for rodents from heat and cold. The review revealed that rodents form a very diverse group of mammals, ranging from tiny pigmy mice to big capybaras, from arboreal flying squirrels to subterranean mole rats, from opportunistic omnivores (e.g. Norway rats) to specialist feeders (e.g. the North African fat sand rats that feed on a single family of plants only). It is therefore no surprise that some species thrive well under the conditions that are found in agricultural fields. The review on the population dynamics of the rodent species indicated that they are agricultural pests probably due to the heterogeneous landscape and to the high rotativity of vegetable crop cultivation. They also cause damage to various crops, directly and indirectly, by gnawing, spoilage, contamination and hoarding activities, besides this behavior they have also significance importance in agricultural habitat. The burrowing activities of rodents alter the soil properties around their burrows which improve its aeration, infiltration, increase the water holding capacity and thus encourage plant growth. These properties are beneficial for the soil because they affect absorption of phosphorus, absorption zinc, copper, other nutrients and the uptake of water and thus rodents are known as indicator species in agricultural fields. Our review suggests that wide crop field’s borders, particularly those contiguous to various cropland fields, should be understood as priority sites for nesting, feeding, and cover for the rodent’s fauna. The goal of this review paper is to provide a comprehensive synthesis of understanding regarding rodent habitat and biodiversity in agricultural landscapes.

Keywords: agricultural landscapes, food, indicator species, shelter

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Authors: Samy S. Eleawa, Mahmoud A. Alkhateeb, Fahaid H. Alhashem, Ismaeel bin-Jaliah, Hussein F. Sakr, Hesham M. Elrefaey, Abbas O. Elkarib, Mohammad A. Haidara, Abdullah S. Shatoor, Mohammad A. Khalil

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This effect of Resveratrol (RES) against CdCl2- induced toxicity in the rat testes was investigated. Seven experimental groups of adult male rats were formulated as follows: A) Controls + NS, B) Control+ vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2 +NS, E) CdCl2+ vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH, and testosterone were measured in all groups. Testicular levels of TBARS and Super Oxide Dismutase (SOD) activity were also measured. Epidydidimal semen analysis was performed and testicular expression of Bcl-2, p53 and Bax were assessed by RT-PCR. Also, histopathological changes of testes were examined microscopically and described. Pre and Post administration of RES in cadmium chloride-intoxicated rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. Not only RES attenuated cadmium chloride induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of both pro-apoptotic genes p53 and Bax. Resveratrol protected from and partially reversed cadmium chloride testicular via upregulation of Bcl2 and down regulation of p53 and Bax gene expression. Antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression. These findings have far reaching implications on subfertility and impotency frequently seen in hypertensive as well as metabolic syndrome patients.

Keywords: resveratrol, cadmium, infertility, sperm, testis, metabolic syndrome

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Authors: Rizvi Hasan

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Male factor infertility due to abnormalities in prolactin levels is encountered in a significant proportion. This was a case-control study carried out to determine the effects of prolactin abnormalities in normal males with infertility, recruiting 297 male infertile patients with informed written consent. All underwent a Basic Seminal Fluid Analysis (BSA) and endocrine profiles of FSH, LH, testosterone and prolactin (PRL) hormones using the random access chemiluminescent immunoassay method (normal range 2.5-17ng/ml). Age, weight, and height matched voluntary controls were recruited for comparison. None of the cases had anatomical, medical or surgical disorders related to infertility. Among the controls; mean age 33.2yrs ± 5.2, BMI 21.04 ± 1.39kgm-2, BSA 34×106, a number of children fathered 2±1, PRL 6.78 ± 2.92ng/ml. Of the 297 patients, 28 were hyperprolactinaemic while one was hypoprolactinaemic. All the hyperprolactinaemic patients had oligoasthenospermia, abnormal morphology and decreased viability. The serum testosterone levels were markedly lowered in 26 (92.86%) of the hyperprolactinaemic subjects. In the other 2 hyperprolactinaemic subjects and the single hypoprolactinaemic subject, the serum testosterone levels were normal. FSH and LH were normal in all patients. The 29 male patients with abnormalities in their serum PRL profiles were followed up for 12 months. The 28 patients suffering from hyperprolactinaemia were treated with oral bromocriptine in a dose of 2.5 mg twice daily. The hypoprolactinaemic patient defaulted treatment. From the follow-up, it was evident that 19 (67.86%) of the treated patients responded after 3 months of therapy while 4 (14.29%) showed improvement after approximately 6 months of bromocriptine therapy. One patient responded after 1 year of therapy while 2 patients showed improvements although not up to normal levels within the same period. Response to treatment was assessed by improvement in their BSA parameters. Prolactin abnormalities affect the male reproductive system and semen parameters necessitating further studies to ascertain the exact role of prolactin on the male reproductive tract. A parallel study was carried out incorporating 200 male white rats that were grouped and subjected to variations in their serum PRL levels. At the end of 100 days of treatment, these rats were subjected to morphological studies of their male reproductive tracts.Varying morphological changes depending on the levels of PRL changes induced were evident. Notable changes were arrest of spermatogenesis at the spermatid stage, a reduced testicular cellularity, a reduction in microvilli of the pseudostratified epithelial lining of the epididymis, while measurement of the tubular diameter showed a 30% reduction compared to normal tissue. There were no changes in the vas deferens, seminal vesicles, and the prostate. It is evident that both hyperprolactinaemia and hypoprolactinaemia have a direct effect on the morphology and function of the male reproductive tract. The morphological studies carried out on the groups of rats who were subjected to variations in their PRL levels could be the basis for infertility in male human beings.

Keywords: male factor infertility, morphological studies, prolactin, seminal fluid analysis

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Authors: Zahra Ashraf

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Flax and pumpkin seeds are a rich source of unsaturated fatty acids, antioxidants and fiber, known to have anti-atherogenic properties. Hypercholesterolemia is a state characterized by the elevated level of cholesterol in the blood. This research was designed to study the effect of flax and pumpkin seeds powder mixture on hypercholesterolemia and body weight. Rat’s species were selected as human representative. Thirty male albino rats were divided into three groups: a control group, a CD-chol group (control diet+cholesterol) fed with 1.5% cholesterol and FP-chol group (flaxseed and pumpkin seed powder+ cholesterol) fed with 1.5% cholesterol. Flax and pumpkin seed powder mixed at proportion of (5/1) (omega-3 and omega-6). Blood samples were collected to examine lipid profile and body weight was also measured. Thus the data was subjected to analysis of variance. In CD-chol group, body weight, total cholesterol TC, triacylglycerides TG in plasma, plasma LDL-C, ratio significantly increased with a decrease in plasma HDL (good cholesterol). In FP-chol group lipid parameters and body weights were decreased significantly with an increase in HDL and decrease in LDL (bad cholesterol). The mean values of body weight, total cholesterol, triglycerides, low density lipoprotein and high density lipoproteins in FP-chol group were 240.66±11.35g, 59.60±2.20mg/dl, 50.20±1.79 mg/dl, 36.20±1.62mg/dl, 36.40±2.20 mg/dl, respectively. Flaxseed and pumpkin seeds powder mixture showed reduction in body weight, serum cholesterol, low density lipoprotein and triglycerides. While significant increase was shown in high density lipoproteins when given to hypercholesterolemic rats. Our results suggested that flax and pumpkin seed mixture has hypocholesterolemic effects which were probably mediated by polyunsaturated fatty acids (omega-3 and omega-6) present in seed mixture.

Keywords: hypercolesterolemia, omega 3 and omega 6 fatty acids, cardiovascular diseases

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Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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