首页> 外文期刊>Journal of biochemical and molecular toxicology >Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation
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Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

机译:二甲双胍和体米素通过调节氧化还原状态和炎症,在大鼠中诱导肝脏毒性的保护剂

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The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor-alpha, prostaglandin E_2), apoptosis (terminal deox-ynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose-dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX-2 and iNOS immunoreactivity scores, further strengthened these findings. The hepa-toprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long-term CsA treatment to maintain their liver and kidney functions.
机译:由于环孢素A(CsA)的肝毒性和肾毒性,其作为免疫抑制剂的使用通常受到限制。本研究旨在评估二甲双胍和水飞蓟素对环孢素a诱导的大鼠肝肾毒性模型的保护作用。该研究包括七组Wistar白化大鼠(每组n=6):正常对照组、实验对照组(仅CsA,25 mg/kg)、CsA+二甲双胍(50和500 mg/kg)、CsA+水飞蓟素(50和200 mg/kg)和CsA+维生素E(100 mg/kg)。所有药物均通过口服灌胃每天给药21天,并对其对血清器官功能标志物(血清谷氨酸丙酮酸转氨酶、血清谷氨酸草酰乙酸转氨酶、胆红素、尿素/血尿素氮、肌酐)、氧化应激标志物(硫代巴比妥酸反应物质、谷胱甘肽、超氧化物歧化酶)水平的影响进行评估,炎症(亚硝酸盐、髓过氧化物酶、肿瘤坏死因子α、前列腺素E_2)、凋亡(末端脱氧核苷酸转移酶dUTP缺口末端标记阳性)以及组织组织学、环氧合酶(COX)-2和诱导型一氧化氮合酶(iNOS)免疫反应性。二甲双胍和水飞蓟素与环孢素a合用以剂量依赖性方式改善肝脏和肾脏的功能损害。在使用两种试验药物治疗后,还观察到组织氧化应激、炎症和凋亡标志物水平的显著和可比改善。组织学评分以及COX-2和iNOS免疫反应评分的正常化进一步加强了这些发现。二甲双胍和水飞蓟素的hepa保护作用和肾脏保护作用与参考药物维生素E的作用相似。本研究的结果表明,二甲双胍和水飞蓟素在接受长期CsA治疗的患者中具有临床应用潜力,以维持其肝和肾功能。

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