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橙皮苷和姜黄素对 5-氟尿嘧啶诱导的小鼠肾毒性的保护作用。

The protective effects of hesperidin and curcumin on 5-fluorouracil-induced nephrotoxicity in mice.

机构信息

Department of Physiology, Veterinary Faculty, Kafkas University, Kars, Turkey.

Department of Physiology, Veterinary Faculty, Ataturk University, Erzurum, Turkey.

出版信息

Environ Sci Pollut Res Int. 2021 Sep;28(34):47046-47055. doi: 10.1007/s11356-021-13969-5. Epub 2021 Apr 22.

Abstract

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)-treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU-induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU-induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU-induced nephrotoxicity.

摘要

肾毒性是氟尿嘧啶(5-FU)治疗的癌症患者的一个非常重要的并发症。氧化应激增加、肾损伤和细胞凋亡在 5-FU 引起的肾毒性发病机制中起重要作用。在这项研究中,确定了两种天然化合物橙皮苷和姜黄素对 5-FU 诱导的实验性小鼠肾损伤的保护作用。5-FU 的应用导致严重的组织病理学变化和严重的肾衰竭,血清尿素和肌酐水平升高。此外,还证明了 5-FU 诱导的肾损伤会增加丙二醛(MDA)的水平,降低超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)的活性和谷胱甘肽(GSH)水平。此外,5-FU 会导致 caspase-3 和 8-OHdG 免疫阳性细胞增加,从而导致肾组织细胞凋亡和 DNA 损伤。然而,橙皮苷和姜黄素的高剂量治疗显著改善了 5-FU 引起的氧化应激/脂质过氧化、细胞凋亡/DNA 损伤和肾功能障碍。基于这些数据,我们的结果表明,橙皮苷和姜黄素可能被用作治疗 5-FU 诱导的肾毒性的新的有前途的药物。

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