Ateşşahín Ahmet, Ceríbaşi Ali Osman, Yuce Abdurrauf, Bulmus Ozgür, Cikim Gürkan
Department of Pharmacology and Toxicology, Faculty of Medicine, Firat University, Elaziğ, Turkey.
Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):121-6. doi: 10.1111/j.1742-7843.2006.00015.x.
The aim of this study was to investigate the possible protective role of antioxidant treatment with ellagic acid on cisplatin-induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in the cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The effects of ellagic acid on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GSH peroxidase) and catalase activities and histopatological examinations. Administration of cisplatin to rats induced a marked renal failure, characterized by significant increases in plasma creatinine, urea and calcium concentrations. Cisplatin also induced oxidative stress, as indicated by increased kidney tissue concentrations of malondialdehyde, and reduced activities of GSH peroxidase and catalase. Furthermore, treatment with cisplatin caused a marked tubular necrosis, degeneration and desquamation, luminal cast formation, karyomegaly, tubular dilatation, interstitial mononuclear cell infiltration and inter-tubular haemorrhagia. Ellagic acid markedly reduced elevated plasma creatinine, urea and calcium levels and counteracted the deleterious effects of cisplatin on oxidative stress markers. In the same way, ellagic acid ameliorated cisplatin-induced pathological changes including tubular necrosis, degeneration, karyomegaly, tubular dilatation when compared to the cisplatin alone group. These results indicate that the antioxidant ellagic acid might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat, but not enough to inhibit cisplatin-induced renal dysfunction.
本研究旨在采用生化和组织病理学方法，探讨鞣花酸抗氧化治疗对顺铂诱导的肾毒性可能具有的保护作用。成年雄性Sprague-Dawley大鼠被随机分为四组。对照组接受0.9%生理盐水；鞣花酸组动物仅接受鞣花酸（10mg/kg）；顺铂组动物仅接受顺铂（7mg/kg）；顺铂+鞣花酸组动物在给予顺铂后接受10天的鞣花酸治疗。通过检测血浆肌酐、尿素、钠和钙浓度；肾组织丙二醛、还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH过氧化物酶）和过氧化氢酶活性以及组织病理学检查，评估鞣花酸对顺铂诱导的肾毒性的影响。给大鼠注射顺铂会导致明显的肾衰竭，其特征为血浆肌酐、尿素和钙浓度显著升高。顺铂还会诱导氧化应激，表现为肾组织丙二醛浓度升高以及GSH过氧化物酶和过氧化氢酶活性降低。此外，顺铂治疗会导致明显的肾小管坏死、变性和脱落、管腔内管型形成、核肿大、肾小管扩张、间质单核细胞浸润和肾小管间出血。鞣花酸显著降低了血浆肌酐、尿素和钙的升高水平，并抵消了顺铂对氧化应激标志物的有害影响。同样，与单独使用顺铂组相比，鞣花酸改善了顺铂诱导的病理变化，包括肾小管坏死、变性、核肿大、肾小管扩张。这些结果表明，抗氧化剂鞣花酸可能对大鼠顺铂诱导的肾毒性和氧化应激具有保护作用，但不足以抑制顺铂诱导的肾功能障碍。
