Search results for: normotensive rats

Authors: Fatimah A. Alhomaid, Nadia H. Mahmoud, Maha A. Al-Qaraawi

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The present study was designed to induce hyperhomocysteinemia (HHcy) in elderly male and female rats. Also,to evaluate, the effect of (HHcy) as a risk factor for cerebrovascular disease and brain atrophy and folate supplementation on serum levels of Hcy, total cholesterol, low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides, pyridoxal phosphate , folate also, histopathological examination of brain and cerebrovascular vessels In this work 50 male and 50 female elderly albino rats were used and divided into five groups. The first group served as control, the second and third group received two different dose of L-methionine, the fourth and fifth group received fortified diet with folate powder plus L-methionine. Our results showed that homocysteine levels in male and female rats that received low and high dose of methionine were higher than in the control group, while the levels of folate significantly decreased in male rats only. Induced hyperhomocysteinemia in elderly male and female rats led to significant increase in serum level of cholesterol, LDLc and triglycerides but serum level of HDLc were significantly lower in methionine treated male and female rats than in control. Our results showed that a strong positive correlation between all these parameters and homocysteine except HDLc levels which correlate negatively to Hcy levels. Administration of folate to methionine treated male rats led to insignificant changes in the level of cholesterol when compared to control group but this level was found to be significantly decrease in female rats received small dose of methionine. When the level of cholesterol compared to the same dose of methionine treated group we found a significant decrease in both male and female rats. LDLc and triglycerides level significantly decrease in male rats only versus the control rats, while when compared to low and high dose of methionine a significant decreased occurs. A significant increase in serum level of HDLc in male and female rats when compared to both control and methionine treated groups. In male and female rats supplemented with folate we found an increased serum levels of folate when compared to rats received both dose of methionine. The levels of pyridoxal phosphate significantly decreased in all treated rats compared to the control group and its level were increased with supplementation of folate versus the rats received small and large dose of methionine. It can be concluded that hyperhomocysteinemia may be an additional risk factor for cerebrovascular atherosclesosis and brain atrophy in elderly people and diatery supplementation with folate blocking the activity of homocysteine and may be considered as a therapeutic possibility.

Keywords: hyperhomocysteinemia, brain atrophy, cerebrovascular, L-methionine, pyridoxal phosphate

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Authors: Sobhy El-Sohaimy, Abduvali Toshev, Hanem Mansour

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(1) Objective: The main objective of the current study was to evaluate in an In Vitro and In Vivo, the potential activity of olive leaves extract (OLE) in the treatment and/or preventing the diabetes mellitus type II and related implications; (2) Methodology: Five groups of male rats were used in the current study: group (1)- negative control (normal); group (2)- positive control, streptozotocin (STZ) induced rats; group (3)-diabetic rats treated with metformin (200 mg/kg) plus OLE (200 mg/kg); group 4- diabetic rats treated with metformin (200 mg/kg); group 5- diabetic rats treated with OLE (200 mg/kg). A four-week regime of oral treatment was administered once daily; (3) Results: Diabetic rats treated with metformin + OLE clearly showed normal blood glucose level (121.67 ± 5.49 mg/dl), and glycated hemoglobin (HbA1c) (3.70 ± 0.10%). The combination of metformin + OLE obviously showed a superior improvement in the lipid profile (TG, TC, HDL and LDL) compared to both metformin and OLE individually. The histological examination revealed that the combination of metformin + Olive leaves extract successfully repaired of the liver, kidneys, and pancreatic tissues in diabetic rats to be near to the normal status; (4) Conclusion: Finally, it can be concluded that, the combination of metformin and OLE exhibited a superior improvement than metformin and OLE individually which emphasized the promising adjuvant role of the OLE in the treatment protocol of diabetes mellitus type II.

Keywords: olive (olea europaea) leaves extracts, hypoglycemic agents, cytotoxicity, nitic oxide scavenging activity, α-glucose oxidase inhibitor

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Authors: Amina Bouzitouna, Kheireddine Ouali, Sandra Amri, Houria Rahmoun, Mourad Bensouilah

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Aim of this study: To evaluate the effect of Cisthanche tinctoria treatment on maternal-fetal outcome and antioxidant systems of streptozotocin-induced diabetic rats. Materials and methods: Virgin female Wistar rats were injected with 50 mg/kg streptozotocin before mating. Oral administration of an methanolic extract of Cistanche tinctoria was given to non-diabetic and diabetic pregnant rats at doses of 200 mg/kg from 0 to 19th day of pregnancy. At day 20 of pregnancy the rats were killed and a maternal blood sample was collected for the determination Vitamin C (Vit C) and malonaldehyde (MDA). The gravid uterus was weighed with its contents and fetuses were analyzed. Results and conclusion: The data showed that the diabetic dams presented an increased glycemic level, resorption, placental weight, placental index, and fetal anomalies, and reduced VIT C and MDA determinations, live fetuses, maternal weight gain, gravid uterine weight, and fetal weight. It was also verified that Cisthanche tictoria treatment had no hypoglycemic effect, did not improve maternal outcomes in diabetic rats, but it contributed to maintain GSH concentration similarly to non-diabetic groups, suggesting relation with the decreased incidence of visceral anomalies.

Keywords: cistanche tinctoria, diabetes, pregnancy, reproductive outcome, anomaly, orobanchacées

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Authors: Afshin Zahedi, Keivan Jamshidi

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This study was conducted to determine the neurotoxic effects of different doses of ACR on the thoracic axons of the spinal cord of rat. To evaluate this hypothesis in the thoracic axons, amino-cupric silver staining technique of the de Olmos was conducted to define the histopathologic characteristic (argyrophilia) of axonal damage following ACR exposure. For this purpose 60 adult male rats (Wistar, approximately 250 g) were selected. Rats were hosed in polycarbonate boxes as two per each. Randomly assigned groups of rats (10 rats per exposure group, total 5 exposure groups as A, B, C, D and E) were exposed to 0.5, 5, 50, 100 and 500 mg/kg per day×11days intraperitoneal injection (IP injection) respectively. The remaining 10 rats were housed in group (F) as control group. Control rats received daily injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay (LHF) were determined. Weight gains were measured daily prior to injection. Gait scoring involved observation of spontaneous open field locomotion, included evaluations of ataxia, hopping, rearing and hind foot placement, and hindlimb foot splay were determined 3-4 times per week. Gait score was assigned from 1-4. After 11 days, two rats for silver stain, were randomly selected, dissected and proper samples were collected from thoracic portion of the spinal cord of rat. Results did show no neurological behavior in groups A, B and F, whereas severe neurotoxicity was observed in groups C and D. Rats in groups E died within 1-2 hours due to severe toxemia. In histopathological studies based on the de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups A, B and F, while moderate to severe argyrophilic changes were observed in different stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups C and D.

Keywords: acrylamide, rat, axonopathy, argyrophily, de Olmos

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Authors: Dalia O. Saleha, Gehad A. Abdel Jaleela, Sally W. Al-Awdana

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Diabetes mellitus (DM) is known to exacerbate cerebral ischemic injury. The present study aimed to investigate the anti-oxidant and anti-inflammatory effects of oral supplementation of melatonin (MLN) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in streptozotocin (STZ)-induced hyperglycemic rats. Hyperglycemia was induced by a single injection of STZ (55mg/kg; i.p.), six weeks later the cerebral injury was induced by MCAO/Re. Twenty-four hours after the MCAO/Re the MLN (10 mg/kg) was injected for 14 consecutive days. Results of the present study revealed that MCAO/Re in STZ-induced hyperglycemia in rats causes an increase in the oxidative stress biomarkers; it increased brain lipid peroxidation (measured as malondialdehyde; MDA) and brain level of nitric oxide (NO). Moreover, MCAO/Reproduces a prominent increase in the brain inflammatory markers viz. interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis nuclear factor-alpha (TNF-α). Oral treatment of MCAO/Re in STZ-induced hyperglycemic rats with MLN (10 mg/kg) for two weeks restored the brain levels of MDA, GSH, NO, IL-6, IL-1β and the TNF-α. MLN succeeded to suppress the exacerbation of damage in the brain of hyperglycemic rats. These results suggest that daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-oxidant and anti-inflammatory effects in the brain.

Keywords: melatonin, brain injury, cerebral ischemia/reperfusion, hyperglycemia, rats

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Authors: Shalini Adiga, Shashikant Chetty, Jisha, Shobha Kamath

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Background: Moderate impairment of learning and memory has been observed in both type 1 and 2 diabetes mellitus in humans and experimental animals. A Change in glucose utilization and oxidative stress that occur in diabetes are considered the main reasons for cognitive dysfunction. Objective: Costus igneus (CI) which is known to possess hypoglycemic activity was evaluated in this study for its effect on learning and memory in normal and diabetic rats. Methods: Wistar rats were divided into control, CI-alcoholic extract treated normal (250 and 500mg/kg), diabetic control and CI-treated diabetic groups. CI treatment was continued for 4 weeks. For induction of diabetes, a single dose of streptozotocin was injected (30 mg/kg i.p). Entrance latency and time spent in the dark room during acquisition and at 24 and 48h after an aversive shock in a passive avoidance model was used as an index of learning and memory. Glutathione and malondialdehyde levels in brain and blood glucose were measured. Data was analysed using ANOVA. Results: During the three trials in exploration test, the diabetic control rats exhibited no significant change in entrance latency or in the total time spent in the dark compartment. During retention testing, the entrance latency of the diabetic treated groups was two times less at 24h and three times less at 48h after aversive stimulus as compared to diabetic rats. The normal drug-treated rats showed similar behaviour as the saline control. Treatment with CI significantly reduced the raised blood sugar and MDA levels of diabetic rats. Conclusion: Costus igneus prevented the cognitive dysfunction in diabetic rats which can be attributed to its antioxidant and antihyperglycemic activities.

Keywords: Costus igneous, diabetes, learning and memory, cognitive dysfunction

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Authors: Abbassi Daloii Asieh, Yazdani Hoda

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Background and Objective: evidence supports systemic inflammation in obesity and insulin resistance. Apelin that is secreted by adipose tissue plays an important role in the inflammation process and appear act as an anti-inflammatory cytokines. The aim of this study was the effect of eight weeks aerobic training and nitro-L-arginine-methyl ester (L-NAME) on plasma apelin in male’s rats. Materials and Methods: For this purpose, 24 male Wistar rats aged 20 months were randomly assigned into four groups: Control, training, training and L-NAME and L-NAME. Training intervention was eight weeks aerobic exercise (5 time/weekly) at 75-80 (%) of maximal oxygen consumption. All rats were killed 72 hours after lasted exercise session; blood samples collected and plasma were stored. Data was analyzed by one way ANOVA and Tucky Test. A p value less than 0.05 was considered statistically signigcant. Results: The results showed that after eight weeks of endurance training exercise Apelin plasma compared to the control group did not change significantly. Also, the results showed that there was significant difference in plasma Apelin between groups(P > 0/05). Also, the results showed no significant difference between the insulin levels and glucose of four groups (P > 0/05). Conclusion: It seems that aerobic exercise plasma Apelin levels in male rats is not affected. On the other hand, nitric oxide inhibitors can reduce levels of plasma Apelin.

Keywords: aerobic training, L-NAME, plasma Apelin, male’s rats

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Authors: N. Uchegbu Nneka

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This study was conducted to investigate the effect of the antioxidant activity of germinated African Yam Bean (AYB) on oxidative stress markers in alloxan-induced diabetic rat. Rats were randomized into three groups; control, diabetic and germinated AYB–treated diabetic rats. The Total phenol and flavonoid content and DPPH radical scavenging activity before and after germination were investigated. The glucose level, lipid peroxidation and reduced glutathione of the animals were also determined using the standard technique for four weeks. Germination increased the total phenol, flavonoid and antioxidant activity of AYB extract by 19.14%, 32.28%, and 57.25% respectively. The diabetic rats placed on germinated AYB diet had a significant decrease in the blood glucose and lipid peroxidation with a corresponding increase in glutathione (p<0.05). These results demonstrate that consumption of germinated AYB can be a good dietary supplement in inhibiting hyperglycemia/hyperlipidemia and the prevention of diabetic complication associated with oxidative stress.

Keywords: African yam bean, antioxidant, diabetes, total phenol

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Authors: Samah Oda, Asmaa Khafaga, Mohammed Hashim, Asmaa Khamis

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Toxicity of hydroxyurea (HU), a treatment for certain tumors, polycythemia, and thrombocytosis, was evaluated in rats in one-month toxicity study. Sixty male albino rats were equally classified into four groups. Rats received daily oral gavage of HU in 0, 250, 500, and 750 mg/kg b.wt. Chemical and histopathological assessment of liver, lung, spleen, and bone marrow was performed at 10, 20, and 30 days of the experiment. No significant change was reported in alanine aminotransferase (ALT), aspartate aminotransferase (AST), globulin, and albumin/ globulin ratio during the experiment. Significant decreases in alkaline phosphatase (ALP) and total albumin were reported in rats received 500 and 750 mg/kg b.wt of HU. In addition, total cholesterol level increased significantly after 10 days; however, it significantly decreased after 20 and 30 days of the experiment. Moreover, hepatocytic vacuolation and necrosis with portal inflammatory infiltrates were reported along experimental periods. Pulmonary congestion, hemorrhage, interstitial mononuclear infiltration, peribronchitis, and bronchial epithelial necrosis were also reported. Severe lymphocytic necrosis in spleen and severe loss of hematopoietic cells and replacement with corresponding adipose tissue in bone marrow tissues was demonstrated. In conclusion, HU could be able to induce severe dose and time-dependent hepato-pulmonary toxicity and lymphoid depression in rats.

Keywords: hydroxyurea, hepato-pulmonary toxicity, lymphoid depression, histopathology

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Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

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Background: The use of nanoparticles for medication delivery offers the possibility of avoiding the negative effects of systemic antibiotic dosing as well as antibiotic resistance in bacteria. Aim of the study: The goal of this study was to see the efficiency of local administration of tetracycline loaded on nano chitosan in the treatment of the induced infection of the albino rats gingiva with Porphyromonas gingivalis through Immunohistochemical localization of Interleukin-1beta (IL-1β) as a proinflammatory cytokine.Material and methods: Fifty adult male albino rats 150 - 180 grams body weight used in this investigation. Any changes in rats’ weights were detected. The male albino rats were divided haphazardly into five groups as Group I involved ten rats; they served as a normal negative control group. Group II involved ten rats; they were infected once with P.gingivalis that was injected into the interdental gingiva. Group III involved ten rats; they were subjected to the same procedure as group II and then to daily injection at the site of infection with diluted tetracycline powder. Group IV involved ten rats; they were subjected to the same procedure as group II and then to daily injection of nano Chitosan at the site of injection. Group V involved ten rats; they were subjected to the same procedure as group II and then to daily injection of tetracycline loaded on nano Chitosan at the site of injection. After rats had been euthanized, the extraction and preparation of their gingiva were carried out in order to examine histologically and immunohistochemically. Results: The light microscopic results of groups II, III, and IV showed degeneration represented by swollen epithelial cells, collagen fibers dissociation of the connective tissue of lamina propria, and areas of basement membrane discontinuation, while groups I and V showed an almost normal histological picture of gingival tissue. Immunohistochemical results showed a significant difference in Group II and III when compared to control. No significant difference appears in group V when compared to the control (group I). Conclusion: Using nanochitosan as a carrier for tetracycline is a new technology to get over the increasing resistance of tetracycline.

Keywords: immunohistochemistry, P.gingivalis, nano-chitosan, tetracycline, periodontitis

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Authors: Ç. Gökçek-Saraç, Ş. Özen, N. Derin

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The N-methyl-D-aspartate (NMDA)-dependent pathway is the major intracellular signaling pathway implemented in both short- and long-term memory formation in the hippocampus which is the most studied brain structure because of its well documented role in learning and memory. However, little is known about the effects of RF-EMR exposure on NMDA receptor signaling pathway including activation of protein kinases, notably Ca²⁺/calmodulin-dependent protein kinase II alpha (CaMKIIα). The aim of the present study was to investigate the effects of acute and chronic 900 MHz RF-EMR exposure on both passive avoidance behaviour and hippocampal levels of CaMKIIα and its phosphorylated form (pCaMKIIα). Rats were divided into the following groups: Sham rats, and rats exposed to 900 MHz RF-EMR for 2 h/day for 1 week (acute group) or 10 weeks (chronic group), respectively. Passive avoidance task was used as a behavioural method. The hippocampal levels of selected kinases were measured using Western Blotting technique. The results of passive avoidance task showed that both acute and chronic exposure to 900 MHz RF-EMR can impair passive avoidance behaviour with minor effects on chronic group of rats. The analysis of western blot data of selected protein kinases demonstrated that hippocampal levels of CaMKIIα and pCaMKIIα were significantly higher in chronic group of rats as compared to acute groups. Taken together, these findings demonstrated that different duration times (1 week vs 10 weeks) of 900 MHz RF-EMR exposure have different effects on both passive avoidance behaviour of rats and hippocampal levels of selected protein kinases.

Keywords: hippocampus, protein kinase, rat, RF-EMR

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Authors: K. Subermaniam, Q. H. M. Saad, S. N. A. Bakhtiar, J. A. Hamid, F. Z .J. Sidek, F. Othman

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Objective: To investigate the effects of virgin coconut oil (VCO) on histomorphometric changes in the aorta and heart of thermoxidized palm oil-fed rats. Methods: Thirty two male Sprague-Dawley rats were divided into four groups: control group fed with normal diet; 5 times heated palm oil-fed group (5HPO) fortified with 15% w/w of 5HPO; VCO group supplemented with 1.42 ml/kg of VCO; and 5HPO + VCO group. The treatment lasted for four months. Upon sacrifice, aortic and heart tissues were processed for light microscopic studies. Results: Light microscopic studies showed thickened intima and media of the aorta in two out of eight rats in the 5HPO group only, while the rest of the rats did not show any thickening of either the intima or media of the aorta. Intima media area (IMA) in the VCO, 5HPO and 5HPO+VCO was significantly increased compared to the control group. Circumferential wall tension (CWT) and tensile stress (TS) in the aorta of 5HPO showed significant increase compared to the other groups. Cardiomyofibre width in 5HPO group showed significant increase in size compared to the control, VCO and 5HPO+VCO groups. Cardiomyofibre nuclear size in the 5HPO group decreased in size significantly compared to the control, VCO and 5HPO+VCO groups. Conclusion: VCO supplementation at a dose of 1.42 ml/kg showed protectives effect on the aorta and heart of thermoxidized palm oil fed rats.

Keywords: aorta, heart, histomorphometric changes, thermoxidized palm oil, virgin coconut oil

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Authors: O. E. Okafor, L. U. S. Ezeanyika, C. G. Nkwonta, C. J. Okonkwo

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The effect of processing on plasma lipid profile and atherogenic indices of rats fed Artocarpus heterophyllus seed diets at different concentrations were investigated. Fifty five rats were used for this study, they were divided into eleven groups of five rats each (one control group and ten test groups), the test groups were fed raw, boiled, roasted, fermented, and soaked diets at 10 % and 40% concentrations. The study lasted for thirty five days. The diets led to significant decrease (p < 0.05) in plasma cholesterol and triacylglycerol of rats fed 10% and 40% concentrations of the diets, and a significant increase (p < 0.05) in high density lipoprotein (HDL) levels at 40% concentrations of the test diets. The diets also produced decrease in low density lipoprotein (LDL), very low density lipoprotein (VLDL), cardiac risk ratio (CRR), atherogenic index of plasma (AIP) and atherogenic coefficient (AC) at 40% concentrations except the soaked group that showed slight elevation of LDL, CRR, AC and AIP at 40% concentration. Artocarpus heterophyllus seeds could be beneficial to health because of its ability to increase plasma HDL and reduce plasma LDL, VLDL, cholesterol, triglycerides and atherogenic indices at higher diet concentration.

Keywords: artocarpus heterophyllus, atherogenic indices, concentrations, lipid profile

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Authors: Rayhana Begum, HongBin Wang, Nur Alam Siddiquee, Md.Yasin Ahmed

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Biotin treatment has significant effects on blood glucose, and pharmacological doses of biotin improve hyperglycemia. The present study was aimed to investigate the efficacy and safety of biotin in combination with canagliflozin in improving glycemic control on High Fat Diet-induced diabetes in Rats. Thirty male rats were divided into five groups (six rats /group): control, high fat diet (HFD), canagliflozin (CAG), biotin (BIO), and CAG + BIO. The treatments with CAG and /or BIO significantly reduced the body weight gain, blood glucose and HbA1c levels, whereas CAG in combination with BIO revealed greater glycemic improvement than CAG monotherapy. The treatment with CAG and /or BIO causes significant change in lipid profile and CK level while the treatment with CAG in combination with BIO showed better results as compared with CAG monotherapy. Furthermore, combination of biotin with CAG improved the pancreatic and cardiac damage when compared with other treated groups.

Keywords: canagliflozin, biotin, HbA1c, lipid profile

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Authors: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre

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Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin

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Authors: Sheila R. Pai, Rekha D. Kini, Amrutha Mary

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Objective: To assess and compare the cardiac autonomic activity after mental stress among the wards of normal and hypertensive parents. Methods: The study included 67 subjects, 30 of them had a parental history of hypertension and rest 37 had normotensive parents. Subjects were divided into control group (wards of normotensive parents) and Study group (wards of hypertensive parents). The height, weight were noted, and Body Mass Index (BMI) was also calculated. The mental stress test was carried out. Blood pressure (BP) and electro cardiogram (ECG) was recorded during normal breathing and after mental stress test. Heart rate variability (HRV) analysis was done by time domain method HRV was recorded and analyzed by the time-domain method. Analysis of HRV in the time-domain was done using the software version 1.1 AIIMS, New Delhi. The data obtained was analyzed using student’s t-test followed by Mann-Whitney U-test and P < 0.05 was considered significant. Results: There was no significant difference in systolic blood pressure and diastolic blood pressure (DBP) between study group and control group following mental stress. In the time domain analysis, the mean value of pNN50 and RMSSD of the study group was not significantly different from the control group after the mental stress test. Conclusion: The study thus concluded that there was no significant difference in HRV between study group and control group following mental stress.

Keywords: heart rate variability, time domain analysis, mental stress, hypertensive

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Authors: Abdul Rohim Tualeka, Erick Caravan K. Betekeneng, Ramdhoni Zuhro, Reko Triyono, M. Sahri

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It has been widely reported incidence caused by acute and chronic effects of exposure to ammonia in the working environment in Indonesia, but ammonia concentration was found to be below the threshold value. The purpose of this study was to determine the safety limit concentration of ammonia in the working environment through the expression of CD8 as a reference for determining the threshold value of ammonia in the working environment. This research was a laboratory experimental with post test only control group design using experimental animals as subjects experiment. From homogeneity test results indicated that the weight of white rats exposed and control groups had a homogeneous variant with a significant level of p (0.701) > α (0.05). Description of the average breathing rate is 0.0013 m³/h. Average weight rats based group listed exposure is 0.1405 kg. From the calculation IRS CD8, CD8 highest score in the doses contained 0.0154, with the location of the highest dose of ammonia without any effect on the lungs of rats is 0.0154 mg/kg body weight of mice. Safe Human Dose (SHD) ammonia is 0.002 mg/kg body weight workers. The conclusion of this study is the safety limit concentration of ammonia gas in the working environment of 0,025 ppm.

Keywords: ammonia, CD8, rats, safe limits concentration

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Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

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Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

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Authors: Dina F. Mansour, Dalia O. Saleh, Rasha E. Mostafa

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Cyclophosphamide (CP), the most commonly used chemotherapeutic agent, was reported to cause many side effects including urotoxicity, cardiotoxicity, gonadotoxicity, and hepatotoxicity; this limits its clinical practice. In the present study, the protective effect of genistein (GEN), the major phytoestrogen in soy products that possesses various pharmacological activities, has been investigated against CP-induced acute liver damage in rats. Forty adult Sprague-Dawley rats were allocated into five groups. The first group received the vehicles and act as normal control. In the other groups, rats were injected with a single dose of CP (200 mg/kg, i.p). The last three groups were pretreated with subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Forty-eight hours following CP injection, rats of all groups were investigated for the serum levels of alanine transaminase and aspartate transaminase, as well as the liver contents of reduced glutathione, malondialdehyde, nitrite, interleukin-1β, and myeloperoxidase. Histopathological examination of liver tissues was also conducted. CP resulted in acute liver damage in rats as evidenced by alteration of liver function biomarkers, oxidative stress, and inflammatory markers; that was confirmed by the histopathological outcomes. Pretreatment of rats with GEN significantly protected against CP-induced deterioration of liver function and showed marked anti-oxidant and anti-inflammatory properties that were demonstrated by the biochemical and histopathological findings. In conclusion, the present findings demonstrated the protective effects of GEN against CP-induced liver damage and suggested role of its antioxidant and anti-inflammatory activities.

Keywords: cyclophosphamide, genistein, inflammation, interleukin-1β, liver, myeloperoxidase, oxidative stress

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Authors: Joseph Bamidele Minari

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The anti-jaundice properties of the methanolic extract of Carica papaya leaves on albino rat was evaluated. In order to achieve this, the phytochemical screening of the extract was carried out, and carbon tetrachloride (CCl4) (i.p) was injected into albino rats to induce jaundice. The rats were simultaneously given oral doses of 20 mg/kg, 40 mg/kg, 60 mg/kg, 80 mg/kg and 100 mg/kg (p.o) of methanolic extract of C. papaya. The effects of these extract on total bilirubin concentration, liver ALT AST, GGT activities of the jaundice-induced rats were studied after seven days period of the experiment. Administration of CCl4 alone to the rats significantly increased (p<0.05) total bilirubin concentration while the activities of ALT, AST, and GGT in the liver when compared to controls which received distilled water (p.o) was significantly lower (p<0.05). Simultaneous treatment of CCl4 injection, and oral administration of different doses of the C. papaya extract significantly reduced (p<0.05) total bilirubin concentration in the serum while the liver ALT AST, GGT activities significantly increased (p < 0.05). However, the lowest significant reduction (p<0.05) of bilirubin concentration was observed with simultaneous administration of 60mg/kg of the extract on the rats. This study suggests that the extract of C. papaya leaves possess the phytochemicals that have anti-jaundice properties.

Keywords: carica papaya, jaundice, herbal medicine, liver, rat

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh P. Paudyal, John R. Falck, Kafait U. Malik

Abstract:

We hypothesized that 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics such as N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE) may be beneficial for preventing mortality due to inflammation induced by lipopolysaccharide (LPS). This study aims to assess the effect of 5,14-HEDGE on the LPS-induced changes in nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome. Rats were injected with saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg/kg) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta, and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC, and β-actin proteins as well as interleukin-1β (IL-1β) levels. Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3, and ASC in addition to IL-1β levels were increased. 5,14-HEDGE prevented the LPS-induced changes. Our findings suggest that inhibition of renal, cardiac, and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involved in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats. This work was financially supported by the Mersin University (2015-AP3-1343) and USPHS NIH (PO1 HL034300).

Keywords: 5, 14-HEDGE, lipopolysaccharide, NLRP3, inflammasome, septic shock

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Authors: Sayyed-Javad Ziaolhagh, Mojtaba Hokmabadi

Abstract:

Introduction: Childhood obesity is a serious medical condition that affects children and adolescents even in the central nervous system. Semaphorins also play a role in the inflammatory process of the nervous system. On the other hand, it has been stated that garlic and stevia extracts following aerobic exercise are effective on immune system inflammation in addition to aerobic activity. Materials and Methods: For 15 weeks, 50 3-week-old male Wistar rats were fed with conventional rodent chow for control and a high-fat diet to induce obesity. Obese rats then were randomly assigned into 7 groups (n=5) based on the Lee index: healthy control (C), obese (OBS), obese + garlic (OBS+GAR), obese + Stevia (OBS+STV), obese + aerobic exercise (OBS+EXE), obese + garlic + aerobic exercise (OBS+GAR+EXE), and obese + stevia + aerobic exercise (OBS+STV+EXE). Training groups completed a progressive aerobic running program (at 8-15 m/min, 5-20 min/day, 5 days/week), and Stevia and garlic extract group (250 mg/kg/day, 5 days/week) were given orally once a day. Real-time PCR was used to determine the levels of Semaphorin 4A, and Plexin D1 gene expressions in the hypothalamus. Fold change analysis with ANOVA was performed for statistical analysis, with a significance threshold of P<0.05. Results: Body weight increased significantly in OBS compared to C (p= 0.013), but was not significantly changed in all treatment rats. Moreover, Semaphorin 4A was significantly increased in obese compared to control group (p= 0.041) and after 8 weeks, stevia extract (p=0.006), aerobic exercise (p=0.012) and garlic extract + aerobic exercise (p=0.008) significantly decreased compared to obese rats. In addition, Plexin D1 genes were also found in the hypothalamus of both obese and control rats but were insignificantly up-regulated when compared with the obese group (p=0.950). Conclusion: High-fat diet caused neuroinflammation by elevation of sema4A in obese rats and stevia, stevia with aerobic and garlic with aerobic could reduce this inflammation in rats. Also, none of them could alter Plexin D1.

Keywords: sema 4A, plexin D1, garlic, stevia

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Authors: Hakim Chayeb

Abstract:

Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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Authors: Aman Upaganlawar, Upasana Khairnar, Chandrashekhar Upasani

Abstract:

The present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride-induced spleen toxicity in rats. Male Wistar rats of either sex (200-250g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o), ascorbic acid (40 mg/kg/day, p.o), and combination of protocatechuic acid (20 mg/kg/day, p.o) and ascorbic acid (20 mg/kg/day, p.o) followed by aniline hydrochloride. At the end of treatment period, serum and tissue parameters were evaluated. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (Hemoglobin content, Red Blood Cells, White Blood Cells and Total iron content), tissue parameters (Lipid peroxidation, Reduced glutathione, Nitric oxide content) compared to control group. Histopathology of aniline hydrochloride-induced spleen showed significant damage compared to control rats. Treatment with Protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride-induced spleen toxicity. In conclusion Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride-induced splenic toxicity in rats.

Keywords: aniline, spleen toxicity, protocatechuic acid, ascorbic acid, antioxidants

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Authors: Hala M. Abdelkarem, Abeer H. Gafeer

Abstract:

The metabolic syndrome (Mts) is a constellation of risk factors. The main objective of this study is to compare the ameliorating effect of metformin, lipitor, orilstate, lipoic acid and carnitin on insulin, lipid profile, leptin, adenonectin levels in metabolic syndrom (high fructose fed rats HF). Seventy male albino rats were divided into seven groups. G1: normal control. G2: G7 rats fed HF for 8wks. After four wk HF feeding, G3, G4, G5, G6, and G7 were orally administered (200 mg/kg daily) metformin, lipitor, orilstate, lipoic acid and carnitin respectively. All drugs were adminiseterd once daily. After 8 weeks of feeding, a significant increase in blood glucose level was observed in HF fed rats compared to normal rats, but this increase was significantly decreased after administration of metformin and lipitor. The raised of serum insulin level in HF fed rats was significantly decreased after administration of lipoic, carnitin, metformin. Significant higher concentrations of triglycerides (TG), total cholesterol & low density lipoprotein cholesterol (LDL- C) were observed in HF fed rats and these increases were significantly lowered after the administration of all the previous drugs. There was a significant decrease in serum high density lipoprotein cholesterol (HDL-C) in HF group administration of all drugs alleviates this reduction. The increased of serum leptin level in HF group was decreased significantly in met and orilstate groups. Whereas the reduction of serum adiponectin level in HF fed rats was increased in Lipitor, carnitin, orilstate groups. These data suggested that benefial effect of metformin, lipitor, orilstate, lipoic acid carnitin in reducing risk for people with decreased insulin sensitivity, increased oxidative stress and hyperlipidemia such as those with the metabolic syndrome or type 2 diabetes.

Keywords: metabolic syndrome, diabetes, proinflammation, antioxidants

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Authors: Lotfollah Rezagholizadeh

Abstract:

Background and Aim: Diabetes mellitus is related to high mortality and morbidity caused by the early development of atherosclerosis correlated to diabetic macroangiopathy. The endothelium-derived vasodilator, nitric oxide (NO) has been implicated in the development of vascular complications via the regulation of blood flow, and various antiatherosclerotic actions. Patients with type 2 diabetes (T2D) have a decreased level of endothelial nitric oxide release. In this study we aimed to examine the effect of aquatic seed extract of Cichorium intybus L. (chicory) and metformin (a known prescription drug for diabetes) on NO levels in T2D rats. Methods: Five groups of adult male Wistar rats were used (n=6): Non-diabetic controls without extract treatment (Control), Non-diabetic controls with extract treatment (Chicory-control), T2D rats without extract treatment (NIA/STZ), T2D rats treated with the extract (Chicory-NIA/STZ), and T2D groups that received metformin (100 mg/kg) but no extract (Metformin-NIA/STZ). T2D was induced with intraperitoneal (i.p) injection of niacinamide (NIA, 200 mg/kg), 15 min after an i.p administration of streptozotocin (STZ, 55 mg/kg). Lyophilized chicory extract (125 mg/kg) was dissolved in 0.2 ml normal saline and administered one dose a day. The experiments lasted for 3 weeks after the diabetes induction. NO analysis was performed by assay based on the Griess reaction. Data were reported as the mean ± SD and statistical analysis was performed by ANOVA. Results: Serum nitric oxide levels decreased significantly in NIA/STZ group compared with Control and Chicory-control. Treatment with chicory extract caused a significant increase in serum levels of NO in Chicory-NIA/STZ group compare to NIA/STZ group (p<05). Metformin-NIA/STZ group did not show considerable difference when compared with NIA/STZ, with respect to NO levels. In a group of rats made diabetic by STZ alone (type 1 diabetic rats, T1D), chicory did not have a significant ameliorating effect. Conclusion: In this study, we clearly showed a relationship between low serum nitric oxide levels and diabetes mellitus in rats. The increase in serum nitric oxide by chicory extract is an indication of antiatherogenic effect of this plant. Chicory seed extract was more efficient than metformin in improving the NO levels in NO-deficient T2D diabetic rats.

Keywords: type 2 diabetes mellitus, nitric oxide, chicory, metformin

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Authors: H. Y. Al-Matubsi, G. A. Oriquat, M. Abu-Samak, O. A. Al Hanbali, M. Salim

Abstract:

Background: Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The aims of this study were to evaluate the protective effect of lipoic acid (LA) on fetal outcome and to elucidate changes that may be involved in the mechanism(s) implicit diabetic fetopathy. Methods: Female rats were rendered hyperglycemic using streptozocin and then mated with normal male rat. Pregnant non-diabetic (group1; n=9; and group2; n=7) or pregnant diabetic (group 3; n=10; and group 4; n=8) rats were treated daily with either lipoic acid (LA) (30 mg/kg body weight; groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure cyclooxygenases (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 (PGFM) levels. Maternal liver and plasma total glutathione levels were also determined. Results: Supplementation of diabetic rats with LA was found to significantly (P<0.05) reduce resorption rates in diabetic rats and increased mean fetal weight compared to diabetic group. Treatment of diabetic rats with LA leads to a significant (P<0.05) increase in liver and plasma total glutathione, in comparison with diabetic rats. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas and membranes were characteristic of experimental diabetic gestation associated with malformation. LA treatment to diabetic mothers failed to normalize levels of PGEM to the non-diabetic control rats. However, the levels of PGEM in malformed fetuses from LA-treated diabetic mothers was significantly (P < 0.05) higher than those in malformed fetuses from diabetic rats. Conclusions: We conclude that LA can reduce congenital malformations in the offspring of diabetic rats at day 15 of gestation. However, LA treatment did not completely prevent the occurrence of malformations, other factors, such as arachidonic acid deficiency and altered prostaglandin metabolismmay be involved in the pathogenesis of diabetes-induced congenital malformations.

Keywords: diabetes, lipoic acid, pregnancy, prostaglandins

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Authors: Fatima Mohammed Musa, J. B. Ameh, S. A. Ado, O. S. Olonitola

Abstract:

The study was undertaken to evaluate the phytochemical constituents of extracts of Terminalia avicennioides leaf and the antidiarrhoeal effect of n-butanol fraction of the leaf extract in Swiss albino rats infected with Salmonella Typhimurium and Escherichia coli. Ethanol crude extract of Terminalia avicennioides leaf was dissolved in 1.5 liters of sterile distilled water. The extract solution was partitioned with 250 ml each of chloroform, ethyl acetate and n-butanol solvents (1:1v/v) to obtain soluble fractions from the extract. The leaf extract and its fractions were screened for the presence of phytocompounds using standard analytical methods. The antidirrhoeal activity of n-butanol fraction was evaluated in Swiss albino rats using standard methods. The results of phytochemical screening of extract of Terminalia avicennioides leaf and its fractions, revealed the presence of carbohydrates, alkaloids, tannins, flavonoids, saponins, steroids, triterpens, glycosides and phenols. The results of in vivo activity showed that 60 % of each group of rats infected with 2.0 x 108 cfu/ml viable cells of S. Typhimurium and 2.0 x109 cfu/ml viable cells of E. coli manifested the symptoms of diarrhoea, 72 hours after the rats were challenged with bacteria. Other symptoms observed among the infected animals included, loss of appetite, loss of weight, general body weakness and 40 % mortality in S. Typhimurium infected non treated group of rats. Similarly, 60 %, and 20 % mortality was observed among E. coli infected none treated and E. coli infected antibiotic (metronidazole) treated groups of rats respectively. However, there was a reduction in the number of infected rats defecating watery stools over time among all the infected rats that were treated with n-butanol fraction of the leaf extract and mortality was also not observed in the group, indicating high efficacy of n-butanol fraction of T. avicennioides leaf. The results also indicated that n-butanol can be used as alternative source of antidiarrhoeal agent in the treatment of diarrhoea caused by Salmonella Typhimurium and Escherichia coli. In the light of this, there is a need for further research on the mechanism of action of the candidate fraction of T. avicennioides leaf which could be responsible for the observed in vivo antibacterial activity.

Keywords: antidirrhoeal effect, phytochemical constituents, swiss albino rats, terminalia avicennioides

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Authors: Elham Rouhollahi, Soheil Zorofchian Moghadamtousi, Salma Baig, Mahmood Ameen Abdulla, Zahurin Mohamed

Abstract:

This study was designed to assess cutaneous wound healing potential of hexane extract of Curcuma purpurascens rhizomes (HECP). Twenty-four rats were divided into 4 groups: 1. Negative, 2. Low dose, 3. High dose and 4. Treatment, with 6 rats in each group. Full-thickness incisions with a diameter of 2 cm were made on the back of each rat. Rats were topically treated two times a day for 15 days. Group 1-4 were treated with sterile distilled water, 5% and 10% of extract and intrasite gel, respectively. Masson's trichrome and hematoxylin staining techniques are employed for histological analysis revealed strong wound healing potential closer to that of conventional drug intrasite gel. HECP significantly decreased wound area and an increase in hydroxyproline, cellular proliferation, the number of blood vessels and the level of collagen synthesis was observed. Thus, it could be concluded that HECP possesses strong wound healing potential.

Keywords: Curcuma purpurascens, wound healing, histopathology, hematoxylin staining

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Authors: Igor Sukhotnik

Abstract:

Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.

Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory

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