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维生素 E 和鱼肝油对顺铂诱导的大鼠急性肾损伤的保护作用。

The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats.

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.

Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.

出版信息

Environ Sci Pollut Res Int. 2020 Dec;27(35):44412-44426. doi: 10.1007/s11356-020-10351-9. Epub 2020 Aug 7.

Abstract

Cisplatin (CP) is a highly effective chemotherapeutic agent against neoplasms, but its clinical utility is limited due to the side effects of its dose-dependent nephrotoxicity. Vitamin E (Vit E) and cod liver oil (CLO) are natural substances with chemoprotective effects. The present study was conducted to evaluate the protective effects of Vit E and/or CLO for CP-induced acute kidney injury (AKI) in rats. This study involved 40 mature male Wistar albino rats that were equally allocated into eight groups: Veh, Vit E, CLO, Vit E + CLO, CP, Vit E + CP, CLO + CP, and Vit E + CLO + CP. The co-administration of Vit E and CLO significantly ameliorated CP-induced elevations in serum creatinine (Cr), blood urea nitrogen (BUN), interleukin 1 beta (IL-1β), and interleukin- 6 (IL-6). Further, rats that received Vit E and/or CLO showed significant decrease in malondialdehyde (MDA) and increases in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels in renal tissues, compared to CP-intoxicated rats. Additionally, the treatment restored the normal histological architecture (except for few cast formations) and upregulated the immunostaining area% of aquaporin 3 (AQP3) and downregulated the immunostaining area% of Bcl2 associated X protein (BAX) and inducible nitric oxide synthase (iNOS). The observed effects were stronger in the combination treatment group. The obtained data revealed that Vit E and CLO co-administration protects against the CP-induced AKI more than monotherapy with Vit E or CLO.

摘要

顺铂(CP)是一种针对肿瘤的高效化疗药物,但由于其剂量依赖性肾毒性的副作用,其临床应用受到限制。维生素 E(Vit E)和鱼肝油(CLO)是具有化学保护作用的天然物质。本研究旨在评估 Vit E 和/或 CLO 对 CP 诱导的大鼠急性肾损伤(AKI)的保护作用。本研究涉及 40 只成熟雄性 Wistar 白化大鼠,平均分为 8 组:Veh、Vit E、CLO、Vit E + CLO、CP、Vit E + CP、CLO + CP 和 Vit E + CLO + CP。Vit E 和 CLO 的联合给药显著改善了 CP 诱导的血清肌酐(Cr)、血尿素氮(BUN)、白细胞介素 1β(IL-1β)和白细胞介素-6(IL-6)升高。此外,与 CP 中毒大鼠相比,接受 Vit E 和/或 CLO 的大鼠肾组织丙二醛(MDA)水平显著降低,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)水平显著升高。此外,该治疗恢复了正常的组织学结构(除了少数铸型形成),并上调了水通道蛋白 3(AQP3)的免疫染色面积%,下调了 Bcl2 相关 X 蛋白(BAX)和诱导型一氧化氮合酶(iNOS)的免疫染色面积%。联合治疗组的效果更强。观察到的效果表明,Vit E 和 CLO 的联合给药比单独使用 Vit E 或 CLO 更能保护 CP 诱导的 AKI。

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