Keshk Walaa Arafa, Katary Mohamed Alaa
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
Indian J Clin Biochem. 2017 Mar;32(1):19-25. doi: 10.1007/s12291-016-0564-y. Epub 2016 Apr 5.
Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups. CCl4 (3 ml/kg body weight; biweekly for 4 weeks) was given to group II and III. Carnosine (10 mg/kg body weight; once daily for 4 weeks) was given to group III and VI. Transforming growth factor-β1 (TGF-β1) level by immunoassay and Smad3 mRNA level by real-time PCR were estimated in addition to cytochrome P450 2E1 (CYP2E1) activity, renal functions, redox status assessment and histopathological examination of the kidney. Carnosine significantly improved kidney function, renal redox status, decreased renal CYP2E1 activity, TGF-β1 level and gene expression when compared to CCL4-intoxicated group. The protective effect of carnosine was confirmed by histopathological study.
carnosine has the ability to protect against CCl4-induced nephrotoxicity possibly by alleviating oxidative stress, normalizing kidney histopathological architecture in addition to the disruption of the inflammatory and fibrotic response induced by CCl4.
接触包括药物和环境毒素在内的各种有机化合物会通过自由基的产生导致细胞损伤。本研究使用二肽肌肽来评估其对四氯化碳诱导的肾毒性的作用。60只雄性白化大鼠参与了本研究,并被平均分为四组。第二组和第三组给予四氯化碳(3毫升/千克体重;每两周一次,共4周)。第三组和第六组给予肌肽(10毫克/千克体重;每天一次,共4周)。除了细胞色素P450 2E1(CYP2E1)活性、肾功能、氧化还原状态评估和肾脏组织病理学检查外,还通过免疫测定法估计转化生长因子-β1(TGF-β1)水平,并通过实时聚合酶链反应估计Smad3 mRNA水平。与四氯化碳中毒组相比,肌肽显著改善了肾功能、肾脏氧化还原状态,降低了肾脏CYP2E1活性、TGF-β1水平和基因表达。肌肽的保护作用通过组织病理学研究得到证实。
肌肽具有预防四氯化碳诱导的肾毒性的能力,可能是通过减轻氧化应激、使肾脏组织病理学结构正常化以及破坏四氯化碳诱导的炎症和纤维化反应来实现的。