İstifli Erman Salih, Demir Erkan, Kaplan Halil Mahir, Ateş Kıvılcım Eren, Doran Figen
Department of Biology, Faculty of Science and Letter, Cukurova University, Adana, 01380, Turkey.
Department of Urology, Faculty of Medicine, Cukurova University, Adana, 01380, Turkey.
Cytotechnology. 2019 Oct;71(5):905-914. doi: 10.1007/s10616-019-00333-2. Epub 2019 Aug 1.
Cisplatin is an antineoplastic agent used in the treatment of various types of solid tumors. Despite the dose-dependency of its antineoplastic effect, the high risk for nephrotoxicity frequently precludes the use of higher doses. α-Linolenic acid (ALA), a carboxylic acid having three cis double bonds, is an essential fatty acid required for health and can be acquired via foods that contain ALA or supplementation of foods high in ALA. Previous studies have shown that ALA demonstrates anti-cancer, anti-inflammatory, and anti-oxidative effects. In this study, we show the protective effect of ALA on cisplatin-induced renal toxicity associated with oxidative stress in mice using biochemical parameters. The mice were randomly assigned into four experimental groups. Group 1 (control group) were administered physiological saline solution for 9 days; group 2 (ALA group) received 200 mg/kg alpha-linolenic acid via gavage for 9 days; group 3 (CIS group) received 100 mg/kg intraperitoneal (i.p.) CIS for 9 days; and group 4 (ALA + CIS group) received 100 mg/kg i.p. CIS and followed by ALA 200 mg/kg via gavage for 9 days. Alpha-linolenic acid significantly reduced the expression of myeloperoxidase (MPO), phospholipase A2 (PLA), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the ALA + CIS group compared to the CIS group. Furthermore, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) quantities were significantly elevated in the ALA + CIS group when compared to the CIS group. ALA significantly decreased the levels of Bax and cleaved caspase-3, while significantly increasing the level of bcl-2, an anti-apoptotic protein, in the ALA + CIS group than in the CIS group. Finally, histopathological examination in renal tissue showed that the significant edematous damage induced by CIS administration alone was reduced in ALA + CIS group. In conclusion, our findings show that ALA is beneficial to CIS-induced nephrotoxicity in mice via its anti-inflammatory and anti-oxidative effects.
顺铂是一种用于治疗各种实体瘤的抗肿瘤药物。尽管其抗肿瘤作用具有剂量依赖性，但高肾毒性风险常常限制了更高剂量的使用。α-亚麻酸（ALA）是一种含有三个顺式双键的羧酸，是维持健康所需的必需脂肪酸，可通过食用富含ALA的食物或补充富含ALA的食物来获取。先前的研究表明，ALA具有抗癌、抗炎和抗氧化作用。在本研究中，我们使用生化参数展示了ALA对顺铂诱导的、与小鼠氧化应激相关的肾毒性的保护作用。将小鼠随机分为四个实验组。第1组（对照组）连续9天给予生理盐水溶液；第2组（ALA组）连续9天经口灌胃给予200 mg/kg的α-亚麻酸；第3组（CIS组）连续9天腹腔注射100 mg/kg顺铂；第4组（ALA + CIS组）先腹腔注射100 mg/kg顺铂，随后连续9天经口灌胃给予200 mg/kg的ALA。与CIS组相比，α-亚麻酸显著降低了ALA + CIS组中髓过氧化物酶（MPO）、磷脂酶A2（PLA）、环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达。此外，与CIS组相比，ALA + CIS组中的过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）含量显著升高。与CIS组相比，ALA + CIS组中Bax和裂解的半胱天冬酶-3水平显著降低，而抗凋亡蛋白bcl-2水平显著升高。最后，肾组织的组织病理学检查表明，单独给予顺铂引起的明显水肿性损伤在ALA + CIS组中有所减轻。总之，我们的研究结果表明，ALA通过其抗炎和抗氧化作用对顺铂诱导的小鼠肾毒性有益。
