Perindopril May Improve the Hippocampal Reduced Glutathione Content in Rats

Purpose: Oxidative stress and renin- angiotensin system are both involved in the pathophysiology of most of the systemic and central disorders as well as in aging. Angiotensin converting enzyme (ACE) inhibitors, well known for their cardiovascular beneficial effects, have also shown antioxidant properties in pathologic conditions. This study aimed to evaluate the central effect of ACE inhibitors on oxidative status under no pathologic condition. Methods: Adult male rats were divided into four groups of 9 rats each. Groups were treated orally by perindopril at the doses of 1, 2, 4 mg/kg/day or normal saline as the control for four consecutive weeks. At the end of the treatment period the reduced and oxidized glutathione (GSH and GSSG respectively) and malondialdehyde (MDA), the product of lipid peroxidation, were measured in the rats’ hippocampus. Results: The GSH increased dose dependently and was significantly higher in the 2 mg/kg perindopril treated group than the control group (p<0.05) while the GSSG level remained unchanged. As a consequent, the ratio of GSH to GSSG increased significantly in a dose dependent manner. There was not any significant change in MDA. Conclusion: This study demonstrated that ACE inhibition may cause an increase in GSH as an anti- oxidant defense in the hippocampus

Glutathione-dependent enzymes in the follicular fluid of the first-retrieved oocyte and their impact on oocyte and embryos in polycystic ovary syndrome: A cross-sectional study

Background: Oxidative stress and GSH-dependent antioxidant system plays a key role in the pathogenesis of polycystic ovary syndrome (PCOS). Objective: We compared glutathione peroxidase (GPx) and glutathione reductase activities and reduced glutathione (GSH) levels in serum and follicular fluid (FF) of the first-retrieved follicle and their impact on quality of oocyte and embryo in PCOS women undergoing IVF. Materials and Methods: This cross-sectional study was conducted on 80 pairs of blood samples and FF of the first-retrieved follicle from PCOS women, at the Infertility center of Ghadir Mother and Child Hospital. The mean activity of GPx and GR, also GSH levels in the serum and FF were compared to the quality of the first follicle and resultant embryo. Results: Retrieved oocytes included 53 (66.25%) MII, 17 (21.25%) MI, and 10 (12.5%) germinal vesicles; after IVF 42 (52.50%) embryos with grade I and 11 (13.75%) with grade II were produced. The mean values for all three antioxidants were higher in the FF compared to serum (p &lt; 0.001). Also all of the mean measured levels were significantly higher in the FF of the MII oocytes compared to that of oocytes with lower grades (p = 0.012, 0.006 and 0.012, respectively). The mean GPX activity and GSH levels were significantly higher in the serum (p = 0.016 and 0.012, respectively) and FF (p = 0.001 for both) of the high-quality grade I embryos. Conclusion: GSH-dependent antioxidant system functions more efficiently in the FF of oocytes and embryos with higher quality. Key words: In vitro fertilization, Glutathione, Antioxidant, Oocyte, Embryo.&nbsp

Redox Imbalance and Reproductive Side Effects of Long and Short Term Nitroglycerin Treatment in Rat Uterus

Background: Bioactivation of nitroglycerin (NTG) leads to the production of reactive oxygen species and reactive nitrogen species. The aim of this study was to investigate the effects of NTG treatment on the redox homeostasis in rat uterus around the time of implantation and the number of pups.Materials and Methods: The rats in long-term test groups were treated subcutaneously with NTG (15mg/kg BW) and normal saline (1ml/kg B) in control groups for 4 weeks. Afterwards, they were mated and divided into four groups. Two groups were treated until 5 days after mating. Thereafter, they were sacrificed and the activities of glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase as well as the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the uterus homogenates were measured. In other two groups, treatments were continued until their pups were counted. In the short-term groups, treatments were started after mating, and all above parameters were measured as similar as long-term groups.Results: Long-term NTG treatment significantly increased MDA level and decreased the GPx activity and the pups number compared to the controls (p&lt;0.05), whereas no marked alteration in the activities of GR and CAT and the levels GSH were observed. However, short-term NTG treated groups showed no significant changes in all the parameters mentioned above as compared with the controls.Conclusion: Long-term NTG treatment, unlike short-term treatment, may cause impaired implantation and infertility, but there is also room for further improvement

Protective effects of quercetin against hyperglycemia-induced oxidative stress in hepatic HepG2 cell line

Objective: Hyperglycemia is a severe consequence of diabetes mellitus (DM). Throughinduction of oxidative stress, it plays a major role in the pathogenesis of several complications in DM. Therefore, new strategies and antioxidants should be implemented inthe treatment of DM. Quercetin is a flavonoid with strong antioxidant capacity found dominantly in vegetables, fruits, leaves, and grains. The current study aimed to investigate quercetin protective effects under D-glucose-induced oxidative stress by assessing antioxidant defense enzymes inHepG2 cells as an in vitro model. Materials and Methods: HepG2 cells were cultured with different concentrations of D-glucose (5.5, 30 and 50 mM) and/or 25 μM quercetin for 48 and 72 hr, respectively. The effect of treatments on cellular integrity, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) activity, andcellular levels of glutathione (GSH) and malondialdehyde (MDA) wasdetermined. Results: D-glucose had various effects on intracellular antioxidant defense atdifferent doses and time-points and quercetin could attenuate oxidative stress and modulate antioxidant defenses. Conclusion: The results of this study indicated that flavonoid quercetin could be proposed as an agent protecting hepatic HepG2 cells against oxidative stress associated with hyperglycemia

Evaluation of Potential Effect of Retinoic Acid on the Differentiation of Rat Bone Marrow Mesenchymal Stem Cells into the Beta Cells and Insulin

Background & Objective: Mesanchymal stem cells (MSCs) derived from a variety of human adult tissues and potentiate to self-replicate and differentiate into different cell types. Retinoic acid (RA) is important in embryonic development of pancreas. The effect of RA on transdifferentiation of rat bone marrow mesanchymal stem cells (BMMSCs) into the beta cells was studied. Materials & methods: Rat BMMSCs were prepared by flashing method and confirmed by evaluating of BMMSCs surface markers. BMMSCs were treated in four groups by: 1) rat pancreatic extract (RPE) (250µg/ml) 2) RPE (250µg/ml) + RA (10µM), 3) no treated group as control and 4) ethanol 10% as vehicle and RA(10µM) as control. Insulin secretion was evaluated by ELISA assay. Insulin expression (RT-PCR) were determined. Results: RT-PCR results showed that insulin expression in RPE and RPE + RA groups. Insulin releasing in group RPE + RA was significantly more than group 1, (p-value < 0.05), Wilcoxon test.. Conclusion: Our study showed that RA can promote differentiation of the BMMSCs into the insulin producing cells invitro

EFFECTS OF TEUCRIUM POLIUM ON ORAL GLUCOSE TOLERANCE TEST, REGENERATION OF PANCREATIC ISLETS AND ACTIVITY OF HEPATIC GLUCOKINASE IN DIABETIC RATS

Background and Objective – Hepatotoxicity associated with the hypoglycemic effects of an aqueous extract of Teucrium polium was previously described. In this investigation, the effects of the extract on oral glucose tolerance test, regeneration of pancreatic islets and hepatic glucokinase activity of streptozocin-induced diabetic rats were studied. Methods – An aqueous extract of T. polium was fed by gavage tube to healthy and streptozocin-induced diabetic rats for several days. Oral glucose tolerance, number of pancreatic islets and hepatic glucokinase activity were measured using standard methods and compared between diabetic and healthy rats. Results – In diabetic animals, the aqueous extract caused a significant reduction (p &lt; 0.001) in the level of serum glucose during oral glucose tolerance tests. The number of pancreatic islets per unit area significantly increased (p &lt; 0.01) and glucokinase activity was significantly elevated (p &lt; 0.01) in diabetic animals treated with the extract. Conclusion – Although aqueous extract of T. polium contains some hepatotoxic compounds, it also contains components that are beneficial in the treatment of streptozocin-induced diabetes

Protective Effects of Vitamin E and/or Quercetin Co-Supplementation on the Morphology of Kidney in Cyclosporine A-Treated Rats

Background: Cyclosporine A (CsA) is a nephrotoxic immunosuppressivedrug. Antioxidants might attenuate its toxicity. Inthe present study, the effects of vitamin E and quercetin on themorphology of kidney in CsA-treated rats were investigated.Methods: Six groups of rats were used in this gavage feedingstudy either for 4 or 8 weeks. Groups 1 and 2 received eitherolive oil or 25% ethanol in olive oil per day. Group 3 receivedCsA (25 mg/kg/day) in olive oil. All other groups received CsAplus the following: group 4, vitamin E (100 mg/kg/day) in oliveoil; group 5, quercetin (15 mg/kg/day) in 25% ethanol in oliveoil; and group 6, vitamin E plus quercetin. In the final day of thestudy, the animals were sacrificed and kidney sections were preparedfor morphologic studies using light microscopy.Results: Acute morphologic alterations induced by CsA in thekidney tubules included isometric vacuolization, brush borderloss, microcalcification, and presence of inclusion bodies. Smoothmuscle degeneration and necrosis were developed in arterioles.Treatment with vitamin E plus quercetin prevented severe,moderate, and mild abnormalities of the tubules. However fibrosiswas the only microscopic change of the interstitium thatwas not present in animals treated with vitamin E plusquercetin after both periods.Some mild morphological changes of the blood vesselssuch as arteriolar medial smooth muscle degeneration and necrosis,arteriolar myocyte dropout and arteriolar wall hyalinizationcaused by CsA disappeared with administration of vitaminE, quercetin or vitamin E plus quercetin in both periods.Conclusion: Co-administration of vitamin E plus quercetinwith CsA in renal transplant patients may be beneficial inreducing the nephrotoxic effects of CsA

Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats

Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE) has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts) as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde) in the testis of control, untreated and MAE-treated (1 g/day/kg) diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc), by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats. Iran J Med Sci. 2014;39(2):123-129