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 (PLA2), 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.

中文翻译：

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α-亚麻酸可保护小鼠肾细胞免受顺铂诱导的肾毒性。

顺铂是一种抗肿瘤药物，用于治疗各种类型的实体瘤。尽管其抗肿瘤作用具有剂量依赖性，但肾毒性的高风险常常妨碍使用更高剂量。α-亚麻酸（ALA）是一种具有三个顺式双键的羧酸，是健康所需的必需脂肪酸，可以通过含有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。在这项研究中，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。这些小鼠被随机分为四个实验组。第1组（对照组）给予生理盐水溶液9天；第2组（ALA组）灌胃200mg/kg α-亚麻酸，连续9天；第3组（CIS组）接受100mg/kg腹腔内（ip）CIS，持续9天；第 4 组（ALA + CIS 组）接受 100 mg/kg ip CIS，然后通过管饲法 200 mg/kg ALA，持续 9 天。与 CIS 组相比，α-亚麻酸显着降低 ALA + CIS 组中髓过氧化物酶（MPO）、磷脂酶 A2（PLA2）、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）的数量显着升高。与 CIS 组相比，ALA + CIS 组中的 ALA 显着降低了 Bax 和 cleaved caspase-3 的水平，同时显着提高了抗凋亡蛋白 bcl-2 的水平。最后，肾组织的组织病理学检查表明，ALA + CIS 组中单独使用 CIS 引起的明显水肿损伤减轻。总之，我们的研究结果表明，ALA 通过其抗炎和抗氧化作用，有利于 CIS 诱导的小鼠肾毒性。