RESUMO
BACKGROUND AND AIM: Cyclophosphamide therapy is known to be associated with the risk of female infertility as a result of ovarian toxicity. Alpha-lipoic acid (LA) and omega-3 fatty acids are known for their antioxidant and anti-inflammatory activities. The present study investigated the potential protective effect of alpha-LA, omega-3 fatty acids, and its combination against cyclophosphamide-induced ovarian toxicity in rats. MATERIALS AND METHODS: Thirty rats were equally divided into Groups I, II, III, IV, and V. Group I was normal control, wherein the rats were fed with normal feed and water ad libitum. Group II served as cyclophosphamide-induced group, wherein the rats were injected with cyclophosphamide at 75 mg/kg through intraperitoneal route once a week to induce ovarian toxicity. Groups III and IV were treated with alpha-LA at the rate of 25 mg/kg and omega-3 fatty acids at the rate of 400 mg/kg, respectively, in parallel to cyclophosphamide induction as in Group II. Group V animals were coadministered with alpha-LA (25 mg/kg) and omega-3 fatty acids (400 mg/kg) along with cyclophosphamide induction as in Group II. The respective treatments were administered daily through oral route for a period of 30 days. Regularity of estrous cycle was evaluated by vaginal cytology. Post-treatment period, the animals were humanely sacrificed, and the blood samples were subjected to the estimation of follicle-stimulating hormone (FSH) and estrogen. The ovarian tissue was weighed and subjected to histopathology, transmission electron microscopy, estimation of decreased glutathione (GSH), and tumor necrosis factor (TNF)-alpha. RESULTS: Rats treated with cyclophosphamide alone manifested irregularity in estrous cycle, increased FSH, and reduced estrogen levels. The ovaries showed decreased GSH and increased TNF-alpha concentrations. Histopathological and transmission electron microscopic analysis of the ovarian follicles revealed degenerative changes. Administration of alpha-LA and omega-3 fatty acids as well as the combination of both the treatments demonstrated significant normalization of the estrous cycle and antioxidant defense mechanism as well as ameliorated the hormonal profile and histological architecture of the ovarian follicles. However, appreciable synergistic efficacy of the combination therapy (alpha-LA+omega-3 fatty acids) with respect to the monotherapies was not observed in the present study. CONCLUSION: The efficacy of alpha-LA and omega-3 fatty acids against cyclophosphamide-induced ovarian toxicity could be attributed to its antioxidant and anti-inflammatory activities that prevented the oxidative damage to the ovaries caused by cyclophosphamide. Hence, our findings suggest that dietary supplementation of alpha-LA and omega-3 fatty acids in women receiving cyclophosphamide therapy could carry potential benefits in preventing cyclophosphamide-induced infertility in childbearing women.
RESUMO
AIM: The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN) in comparison to silymarin (SLM) against acetaminophen (APAP)-induced hepatotoxicity in rats. MATERIALS AND METHODS: Male Wistar albino rats (n=24) of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days. The mean body weights and biomarkers of hepatotoxicity were estimated on day 0, 4 (confirmation of toxicity), and 15 (at the end of treatment). Hematological parameters were evaluated on day 4 and 15. Antioxidant profile and adenosine triphosphatases (ATPases) were assessed at the end of the experiment. Liver tissues were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. RESULTS: Antioxidant profile, ATPases, and hematological and sero-biochemical parameters were significantly altered, and histopathological changes were noticed in the liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with SLM and RTN, respectively. CONCLUSION: The results of the present investigation enunciated that SLM has potent hepatoprotective activity though the RTN was found superior in restoring the pathological alterations in paracetamol-induced hepatotoxicity in Wistar albino rats.
RESUMO
AIM: A role of thyroid disruption in developmental neurotoxicity of monocrotophos (MCP) and lead is studied. MATERIALS AND METHODS: A total of 24 female rats after conception were randomized into four groups of six each and treated as follows: Group I - Sham was administered distilled water orally. Group II - A positive control was administered methyl methimazole at 0.02% orally in drinking water. Group III - MCP orally at 0.3 mg/kg and Group IV - Lead acetate at 0.2% orally in drinking water. The drug was administered from gestation day 3 through post-natal day 21 in all the groups. Acetylcholinesterase (AChE) inhibition, thyroid profile (thyroid stimulating hormone, T3 and T4), neurodevelopment (brain wet weights, DNA, RNA and protein), and neurobehavioral (elevated plus maze, photoactometry, and Morris water maze) parameters were assessed in pups. A histopathology of thyroid of dams and brain of progeny was conducted. RESULTS: Inhibition of AChE was <20%. Thyroid profile decreased in the treatment groups. Neurodevelopmental and neurobehavioral parameters did not reveal any significant changes. Thyroid architecture was affected significantly with MCP and lead. Cortical layers too were affected. The three layers of cerebellum either had abnormal arrangement or decreased cellularity in all treated groups relating to thyroid disruption. CONCLUSION: MCP and lead might have affected the development of cerebrum and cerebellum via thyroid disruption leading to developmental neurotoxicity.