Search results for: male albino mice

Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

Procedia PDF Downloads 75

Authors: Khairy M. A. Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

Procedia PDF Downloads 174

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

Procedia PDF Downloads 528

Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

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Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

Procedia PDF Downloads 70

Authors: Nina Ivanova

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More than one third of the population and animals are infected with parasitic helminths. It is especially difficult to cure the larval forms of parasites. The larvae of Hymenolepis nana invade the villi of the intestinal mucosa. Toxocara larvae can live in the liver, heart, lungs, brain, eyes, and pancreas. Commercial antiparasitic drugs cannot guarantee a 100% cure after a single course of treatment, because parasite larvae invade the villi of the intestinal mucosa and the anthelmintics do not reach and kill cestode larvae. The aim of this work was to conduct a study of liposomal antihelminthics on the laboratory animals under the certification received from the Committee on Bioethics and Deontology. It has been checked: 1) anthelmintic activity of the liposomal form of fenasal in experimental hymenolepidosis of white mice (larval stage - Hymenolepis nana). 2) anthelmintic activity of the liposomal form of albendazole in experimental toxocariasis of white mice (in the lungs at the stage of larval migration). Since some helminths cause hemolysis of erythrocytes as we used a mixture of polar lipids developed by us with antihemolytic activity to obtain liposomes Fenasal and albendazole were included in the liposome membrane in the ratio of anthelmintic: lipids 1:10. . The average size of liposomes was 180 nm, and the concentration of lipids in liposomes was 1%. The researches were carried out on white male mice who were infected with Hymenolepis Nana invasional eggs in a peroral way with a doze of 100 eggs per animal. On the 5th day after infection, a liposomal fenasal and commercial fenasal were administered orally for comparison. The animals were observed for 15 days. Before the introduction of liposomes and on the 3rd, 5th, 15th day after the administration of the drug, studies were carried out on the presence of helminths in the organs of animals. The liposomal fenasal, when administered orally, had an anthelmintic effect on Hymenolepis Nana cysticercoids at a dose of 25 mg/kg. The percentage of efficiency was 90.06, 91.36 96.85% on days 3, 5, 15, respectively. For comparison, the commercial activity was at a dose of 200 mg/ml, which is 8 times higher than the dose of liposomal fenasal. To evaluate the anthelmintic effect of the liposomal form of albendazole in experimental toxocariasis of white mice (toxascaris in the lungs at the stage of larval migration), studies were also carried out on white mice. The animals were infected with invasive eggs of Toxocara canis, orally, at a dose of 100 eggs per animal. On the 5th day after infection, the liposomal albendazole was administered orally. The efficacy of the study dosage form was determined by counting Larva mirgans larvae in the lungs. The results obtained showed that the liposomal albendazole had the greatest anthelmintic effect on Toxocara larvae at a dose of 2.0 mg/kg, which was 3.75 times less than the therapeutic one. At the same time, the percentage of efficiency was 93.75% on the 3rd day, and 98.66% on the 5th day.

Keywords: hymenolepis, Toxocara, larvae, liposomes

Procedia PDF Downloads 113

Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

Procedia PDF Downloads 158

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w.day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation.

Keywords: antioxidants, doxorubicin, hepatotoxicity, purslane

Procedia PDF Downloads 418

Authors: Wan-Ting Shen, Ching-Liang Hsieh, Yi-Wen Lin

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Electroacupuncture (EA) has been reported effective for many kinds of pain and is a common treatment for acute or chronic pain. However, to date, there are limited studies examining the effect of acupuncture dosage. In our experiment, after injecting mice with Complete Freund’s Adjuvant (CFA) to induce inflammatory pain, two groups of mice were administered two different 15 min EA treatments at 2Hz. The first group received EA at a single acupuncture point (ST36, Zusanli) in both legs (two points), whereas the second group received two acupuncture points in both legs (four points) and the analgesic effect was compared. It was found that double points (ST36, Zusanli and SP6, Sanyinjiao) were significantly superior to single points (ST36, Zusanli) when evaluated using the electronic von Frey Test (mechanic) and Hargreaves’ Test (thermal). Through this study, it is expected more novel physiological mechanisms of acupuncture analgesia will be discovered.

Keywords: anti-inflammation, dose effect, electroacupuncture, pain control

Procedia PDF Downloads 171

Authors: Khairy Mohamed Abdalla Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

Procedia PDF Downloads 100

Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

Procedia PDF Downloads 149

Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

Procedia PDF Downloads 322

Authors: Abu Saleh Mohammad Sowad

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Back in history, muscular and strong male body has always been used to promulgate masculinity; for physically representing supreme manliness there were not many other options. This idealized male figure was proliferated mainly for spreading the notion of male superiority in relation to power and to give a strong base to the social construction of masculinity. This study targets to disclose the perception about the attributes masculinities among the male students of Dhaka city regarding male beautification. It is an attempt to unveil young men’s perspectives regarding their masculinities and beauty. Till the very recent past, beauty was always seen as sole feminine trait in Bangladeshi society. From history we can see men have always been assumed as the ambassador of roughness but in recent time the emergence of fashion-conscious men can be seen, who are slowly occupying a handsome position in the society. Concerning study attempts to bring out the way in which such changing trend of male beauty is perceived among the male students of Dhaka city. What could be the ideologies of these young men who are being involved with it? What is influencing them to be part of such arena which, to a great extent, is still considered as female domain? Is their perception about construction of masculinity is shifting from the so called idealized masculinity? The study tries to find out the answers.

Keywords: masculinity, male beauty, Bangladesh, identity, body

Procedia PDF Downloads 474

Authors: Ahmad Daryani, Yousef Dadimoghaddam, Mehdi Sharif, Ehsan Ahmadpour, Shahabeddin Sarvi, Baghar Hashemi

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Background: Excretory-secretory antigens (ESAs) of Toxoplasma gondii are one of the candidates for immunization against toxoplasmosis. For evaluation of immunization, we determined the kinetics of the distribution of Toxoplasma and parasite load in different tissues of mice immunized by ESAs. Methods: In this experimental study, 36 mice in case (n= 18) and control (n= 18) groups were immunized with ESAs and PBS, respectively. After 2 weeks, mice were challenged intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues (brain, spleen, liver, heart, kidney, and muscle) were collected daily after challenge (1, 2, 3 and last day before death). Parasite load was calculated using Real time QPCR targeted at the B1 gene. Results: ESAs as vaccine in different tissues showed various effects. However, infected mice which received the vaccine in comparison with control group, displayed a drastically decreasing in parasite burden, in their blood and tissues (P= 0.000). Conclusion: These results indicated that ESAs with reduction of parasite load in different tissues of host could be evaluable candidate for the development of immunization strategies against toxoplasmosis.

Keywords: parasitic load, murine toxoplasmosis, immunization, excretory-secretory antigens, real time QPCR

Procedia PDF Downloads 445

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

Procedia PDF Downloads 423

Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

Procedia PDF Downloads 313

Authors: Mahsa Hadipour Jahromy, Sara Rezaii

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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Alireza Barari, Maryam Firoozi, Maryam Ebrahimzadeh, Romina Roohan Ardeshiri, Maryam Kamarloeei

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Background: The The purpose of this study was to evaluate the effect of six-week aerobic training and taxol consumption on interleukin 8 and Plasminogen Activator Inhibitor-1 (PAI-1) in mice with cervical cancer. Material and method: In this experimental study, 40 female C57 mice, eight weeks old, were randomly divided into 4 groups: cancer, cancer-taxol complement, cancer-training and cancer-training - taxol complement with 10 mice in each group. The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/ kg/day, a pure extract of Taxol was injected peritoneal Data were analyzed by t-test, One-way ANOVA and post hoc Bonferron's at the significant level P<0. 05. Results: The results showed that there was a significant difference between mean values of interleukin-8 (P < 0.05, F = 12.25) and the plasminogen activator inhibitor-1 (P < 0.05, P=0.10737) in four groups. A significance level of less than 0.05 in Tukey test for both variables also showed a significant difference between the "control" group and the complementary "exercise" group. Namely, six weeks of aerobic training, along with taxol, have a significant effect on the level of plasminogen activator inhibitor-1 and interleukin-8 mice with cervical cancer. Conclusion: Considering the effect of training on these variables, this type of exercise can be used as a complementary therapeutic approach along with other therapies for cervical cancer.

Keywords: cervical cancer, taxol, endurance training, interleukin 8, plasminogen activator inhibitor-1

Procedia PDF Downloads 183

Authors: Hye Jin Choi, Mirim Jin, Jeong June Choi

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Green tea, which is one of the most popular of tea, contains various ingredients that help health. Epigallocatechin gallate (EGCG) is one of the main active polyphenolic compound possessing diverse biologically beneficial effects such as anti-oxidation, anti-cancer founding in green tea. This study was performed to investigate the anti-diabetic effect of high-purity EGCG ( > 98%) in a spontaneous diabetic mellitus animal model, db/db mouse. Four-week-old male db/db mice, which was induced to diabetic mellitus by the high-fat diet, were orally administered with high-purity EGCG (10, 50 and 100 mg/kg) for 4 weeks. Daily weight and diet efficiency were examined, and blood glucose level was assessed once a week. After 4 weeks of EGCG administration, fasting blood glucose level was measured. Then, the mice were sacrificed and total abdominal fat was sampled to examine the change in fat weight. Plasma was separated from the blood and the levels of aspartate amino-transferase (ALT) and alanine amino-transferase (AST) were investigated. As results, blood glucose and body weight were significantly decreased by EGCG treatment compared to the control group. Also, the amount of abdominal fat was down-regulated by EGCG. However, ALT and AST levels, which are indicators of liver function, were similar to those of control group. Taken together, our study suggests that high purity EGCG is capable of treating diabetes mellitus based in db / db mice with safety and has a potent to develop a therapeutics for metabolic disorders. This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (317034-03-2-HD030)

Keywords: anti-diabetic effect, db/db mouse, diabetes mellitus, green tea, epigallocatechin gallate

Procedia PDF Downloads 187

Authors: Dewi Tristantini, Jason Jonathan

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Coronary Artery Disease (CAD) is one of the deathliest diseases which is caused by atherosclerosis. Atherosclerosis is a disease that plaque builds up inside the arteries. Plaque is made up of fat, cholesterol, calcium, platelet, and other substances found in blood. The current treatment of atherosclerosis is to provide antiplatelet therapy treatment, but such treatments often cause gastrointestinal irritation, muscle pain and hormonal imbalance. Mimusops elengi L.’s leaves can be utilized as a natural and cheap antiplatelet’s source because it contains flavonoids such as quertecin. Antiplatelet aggregation effect of Mimusops elengi L.’s leaves’ wet extract was measured by bleeding time on DDY strain mice with the test substances were given orally during the period of 8 days. The bleeding time was measured on first day and 9th day. Empirically, the dose which is used for humans is 8.5 g of leaves in 600 ml of water. This dose is equivalent to 2.1 g of leaves in 350 ml of water for mice. The extract was divided into 3 doses for mice: 0.05 ml/day; 0.1 ml/day; 0.2 ml/day. After getting the percentage of the increase in bleeding time, data were analyzed by analysis of variance test (Anova), followed by individual comparison within the groups by LSD test. The test substances above respectively increased bleeding time 21%, 62%, and 128%. As the conclusion, the 0.02 ml/day dose of Mimusops elengi L.’s leaves’ wet extract could increase bleeding time better than clopidogrel as positive controls with 110% increase in bleeding time.

Keywords: antiplatelets, atheroschlerosis, bleeding time, Mimusops elengi

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Authors: Leila Anoosheh

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Aim: The aim of this study was to assess The effects of aerobic training on microRNA let-7a expression and levels of tumor tissue IL-6 in mice with breast cancer. Method: Twenty BALB/c c mice (4-5 weeks,17 gr mass) were cancerous by injection of estrogen-dependent receptor breast cancer cells MC4-L2 and divided into two groups: tumor-training(TT) and tumor-control(TC) group. Then TT group completed aerobic training for 6 weeks, 5 days per week (14-18 m/min). After tumor emersion, tumor width and length were measured by digital caliper every week. 48 hours after the last exercise subjects were killed. Tissue sampling were collected and stored in -70ᵒ. Tumor tissue was homogenized and let-7a expression and IL-6 levels were accounted with Real time-PCR and ELISA Kit respectively. Statistical analysis of let-7a was conducted by the REST software. Repeated measures and independent tests were used to assess tumor size and IL-6, respectively. Results: Tumor size and IL-6 levels were significantly decreased in TT group compare with TC group (p<0.05). microRNA let-7a was increased significantly in TT against control group respectively (p=0/000). Conclusion: Reduction in tumor size, followed by aerobic exercise can be attributed to the loss of inflammatory factors such as IL-6; It seems that regarding to up regulation effects of aerobic exercise training on let-7a and down regulation effects of that on IL-6 in mice with breast cancer, This type of training can be used as adjuvant therapy in conjunction with other therapies for breast cancer.

Keywords: breast cancer, aerobic training, microRNA let-7a, IL-6

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Lucia Mavudzi

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Socioeconomic and demographic factors influence male attendance of antenatal care (ANC) activities which are beneficial in improving maternal health and birth outcome. When a male, as the head of the family is expected to solely make decisions of how finances are managed, when and where health services are sought, it impacts on the woman’s health seeking behavior. Using the data from the Zimbabwe Demographic and Health Survey 2010-2011 this paper seeks to assess the prevalence of male ANC attendance in Zimbabwe and factors that influence male ANC attendance. We hypothesized that socioeconomic and demographic factors do not influence male ANC attendance. To achieve the objectives of this paper, descriptive analysis was used to describe the characteristics of men and the Binomial logistic modelling was used to assess the relationship between male ANC attendance and selected socioeconomic and demographic factors. Male ANC attendance was used as the dependent variable, and the independent variables are age, marital status, place of residence, wealth, education, religion and employment. A high percentage of males did not attend ANC with their pregnant partners. Religion, education, and place of residence were found to be significantly associated with male ANC attendance. There was no evidence to show that there was a difference in male ANC attendance by employment, marital status, and age. Findings from this paper are relevant to public health. They will be used to develop strategies and intervention programs to improve pregnant women’s attendance of ANC attendance by involving men in maternal health.

Keywords: antenatal care, male participation, maternal health, socio-economic and demographic factors

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Authors: Teng Zhang, Xuelin Zhang, Shouxiang Lu, Changhai Li

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The existence of animal groups and collective migration are common in nature, and collective behavior is attracting more and more attention of researchers. Previous results have shown that architectural design had an important effect on the process of crowd evacuation. In this paper, collective behavior of mice passing through a middle-exit or corner-exit under panic was investigated. Selfish behavior and herd behavior were easily observed in our video, which caused the congregation with high density near the exit. Triangle structure of congregation formed near the middle-exit while arch structure formed near the corner-exit. It is noteworthy that the exit located at the middle of the wall was more effective for evacuation than at the corner. Meanwhile, the escape sequence of mouse passing through the exit was investigated, and the result showed that the priority depends largely on its location in the congregation. With the level of stimulus increasing, these phenomena still exist. The frequency distributions of time intervals and the burst sizes were also analyzed in this study to explore the secret of collective behavior of mice. These results could provide evidence for the hypothesis or prediction about human behavior in crowd evacuation. However, it is not clear whether the simulated results from different species can correspond to reality or not. Broader comparison among different species about this topic will be eager to be conducted to deepen our understanding of collective behavior in nature.

Keywords: collective behavior, mice, evacuation, exit location

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Authors: Tehmina Aslam

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South-Asian societies elicit a male-dominant hierarchy, socio-economically and politico-religiously. The aim of the study was to examine the contribution of gender to violent extremism in order to devise means for its control in Pakistan. A qualitative case study based on interviews was conducted of de-radicalized former militants who were affiliated to militant organizations such as Sipahe Sahaba Pakistan, Lashkare Jhangvi, Laskhare Taibah, and Jaishe Mohammad, and who resided in Sargodha and Jhang, cities of the Punjab. The study exuded three main findings: first, gender alone was insufficient to motivate a male youth to resort to violent extremism; second, gender segregation made a male youth more vulnerable to an extremist ideology; and third, male gender was more prone to the influence of an extremist misguided religious ideology that pandered to male chauvinistic (societal dogmas constructing a male identity) needs and offered a male youth an opportunity to reinforce male dominance in society. The conclusion drawn was that the confluence of societal dogmas and extremist (religious) ideologies offered the major resistance against preventing violent extremism and, without dealing with both of them simultaneously, the tendency in male youth to resorting to violent extremism could not be dissipated.

Keywords: violent extremism, countering violent extremism, preventing violent extremism, youth

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Authors: Nadia A. Mohamed, Mehrevan M. Abdel-Moniem

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Zingiber officinale (ginger) has been cultivated for medicinal purposes due to their various proprieties both in vitro and in vivo, so we designed to evaluate the ginger’s potential effect on nephrin m RNA expression in cisplatin-induced nephrotoxic rats. Method: Forty male albino rats were divided into group I was injected (IP) with one ml saline, group II(cisplatin) injected (IP) with a single dose of 12 mg/kg cisplatin, group III (ginger) received (PO) 310 mg/kg for 30 successive days, and group IV(cisplatin and ginger) rats received ginger extract (310 mg/kg) daily for 20 successive days (PO), and then on day 20 of ginger extract administration each rat was injected(IP) with a single dose of 12 mg/kg cisplatin. The blood was sampled to assess urea, creatinine (SC), while the levels of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase (PON1) were measured in kidney tissue homogenate. Expression of urinary nephrin gene (nephrin mRNA) was detected using qRT-PCR. Results: Treatment with ginger significantly decreased the levels of kidney function parameters as well as MDA and NO elevated by cisplatin injection, while PON1 was significantly reduced in the cisplatin group. However, the protection of male rats with ginger significantly increased the levels of nephrin gene expression and PON1 compared with the cisplatin-treated group. Our results generated a proposal on the ameliorating effect of ginger on nephrin mRNA gene expression reduction in cisplatin-induced nephrotoxicity.

Keywords: nephrin mRNA, ginger, cisplatin, nephrotoxicity

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Authors: Nora Mohammed Al-Kehayez

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This present investigation was performed to study the effect of low fat yogurt on serum and liver lipids profile of male albino rats (weighing 100 g+or- 5 gram) when fed balanced or high fat high cholesterol diets and given yogurt ad libitum compared with control groups. Rats were divided into 4 groups, each group contains 6 rats. The groups of rats were fed as follows: Group(1) was fed balanced diet + water(control). Group(2) was fed balanced diet + low fat yogurt. Group(3) was fed high fat high cholesterol diet + water(Control). Group(4) was fed high fat high cholesterol diet + low fat yogurt. The obtained results could be summarized as follows: When rats were given low fat yogurt and fed balanced or high fat high cholesterol diets a significantly greater weight gains resulted in comparison with the control groups given water instead of yogurt. The data on the weights of liver and heart expressed' as percentage increased the body weight in case of rats which were fed balanced diet with low fat yogurt while in case of rats which were fed high fat high cholesterol diet with low fat yogurt the increment scenes to be less. Results of serum cholesterol levels in serum of rats were given balanced or high fat high cholesterol diets and consuming low fat yogurt was showed a significant reduction values. However the low fat yogurt produced the highest significant decrease values. The values of serum cholesterol go hand in hand with serum lipoprotein fractions in rats given low fat yogurt with both balanced or high fat high cholesterol diets. An increase of high density lipoprotein HDL-C and a decrease of low density lipoprotein LDL-C values were obtained. When rats ingested low fat yogurt a significant decrease in serum and liver triglycerides content was obtained wether with balanced or high fat high cholesterol diets. Rats consuming high fat high cholesterol diets with water showed a significant increase in liver total lipids, total cholesterol and phospholipides levels in comparison with the same liver parameters in rats given balanced diet with water. Supplement with low fat yogurt significantly suppressed these effects.

Keywords: yogurt, lipids profile, albino, rats

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Authors: H. El-Messiry, M. El-Zainy, D. Ghazy

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Diabetes is a metabolic disease that results in a variety of oral health complications. Green tea is a natural antioxidant proved to have powerful effects against diabetes. The aim of this study was to compare between the effect of insulin and green tea on the Parotid gland of streptozotocin induced diabetic Albino rats by using light and transmission electron microscopy. Forty male Albino rats were divided into control group and diabetic groups. The diabetic group received a single injection of 40 mg/kg of streptozotocin intra-peritoneal under anesthesia and was further subdivided into three subgroups: The diabetic untreated subgroup which was untreated for two weeks, the insulin treated subgroup which has received insulin subcutaneously in a daily dose of 5 IU/kg body weight/day for two weeks and a green tea treated subgroup received a daily dose of 1 ml/ 100 gm body weight intragastrically for two weeks. Rats were terminated and parotid glands were dissected and processed for light and transmission electron microscopic examination. Histological examination of the diabetic untreated subgroup revealed acinar cells with pyknotic and hyperchromatic nuclei with cytoplasmic vacuolations. Ultrastructurally, acinar cells showed nuclear pleomorphism, dilated rough endoplasmic reticulum and swollen mitochondria with damaged cristae. Inflammatory cell infiltration was detected both histologically and ultrastructurally. Ducts showed signs of degeneration with loss of their normal outline and stagnated secretion within the lumen. However, insulin and green tea treated subgroups showed minimal degenerative damage and were almost similar to the control with minimal changes. Treatment of the parotid gland of the streptozotocin induced diabetic rats with GT was closely comparable to the traditional insulin therapy in reducing signs of histological and ultrastructural damage.

Keywords: diabetes, green tea, insulin, parotid

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Authors: S. A. Nirmal, G. S. Asane, S. C. Pal, S. C. Mandal

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Objective: Ficus religiosa Linn (Moraceae) is being used in traditional medicine to improve immunity hence present work was undertaken to validate this use scientifically. Material and Methods: Dried, powdered bark of F. religiosa was extracted successively using petroleum ether and 70% ethanol in soxhlet extractor. The extracts obtained were screened for immunomodulatory activity by delayed type hypersensitivity (DTH), neutrophil adhesion test and cyclophosphamide-induced neutropenia in Swiss albino mice at the dose of 50 and 100 mg/kg, i.p. 70% ethanol extract showed significant immunostimulant activity hence subjected to column chromatography to produce tyrosine rich fraction (TRF). TRF obtained was screened for immunomodulatory activity by above methods at the dose of 10 mg/kg, i.p. Results: TRF showed potentiation of DTH response in terms of significant increase in the mean difference in foot-pad thickness and it significantly increased neutrophil adhesion to nylon fibers by 48.20%. Percentage reduction in total leukocyte count and neutrophil by TRF was found to be 43.85% and 18.72%, respectively. Conclusion: Immunostimulant activity of TRF was more pronounced and thus it has great potential as a source for natural health products.

Keywords: Ficus religiosa, immunomodulatory, cyclophosphamide, neutropenia

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Authors: Omid Ghollipoor Bashiri, Farzam Hatefi

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Dichlorvos a synthetic organophosphate poisons are used as insecticide. These toxins can be used insecticides in agriculture and medicine for destruction and/or eradication of ectoparasites of animals. Studies have shown that Dichlorvos creation seizure effects in different animals. Amlodipine, dihydropyridine calcium channel blockers, widely used for treatment of cardiovascular diseases. Studies have shown that the calcium channel blockers are anticonvulsant effects in different animal models. The aim of this study was to determine the effect of Amlodipine on Dichlorvos-induced seizures in mice. In this experiment, the animals were received different doses of Amlodipine (2.5, 5, 10, 20 and 40 mg/ kg b.wt.) intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg/kg b.wt). After Dichlorvos injection, clonic and tonic seizures, and finally was the fate was investigated. Results showed that Amlodipine dose-dependently reduced the severity of Dichlorvos-induced seizures, so that Amlodipine at a dose of 5mg (The lowest, p<0.05) and 40 mg/kg b.wt. (The highest, p<0.001) which had anticonvulsant effects. The anticonvulsant activity of Amlodipine suggests that possibly due to the antagonistic effect on voltage-dependent calcium channel.

Keywords: dichlorvos, amlodipine, seizures, mice

Procedia PDF Downloads 306

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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