Department of Physiology, Veterinary Faculty, Kafkas University, Kars, Turkey.
Department of Physiology, Veterinary Faculty, Ataturk University, Erzurum, Turkey.
Environ Sci Pollut Res Int. 2021 Sep;28(34):47046-47055. doi: 10.1007/s11356-021-13969-5. Epub 2021 Apr 22.
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.
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。