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橙皮素对顺铂诱导的大鼠肾毒性的肾保护作用:分子和生化证据。

The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India; Department of Pharmacology, Gauhati Medical College, Guwahati 781032, Assam, India.

出版信息

Biomed Pharmacother. 2017 May;89:1207-1215. doi: 10.1016/j.biopha.2017.03.008. Epub 2017 Mar 14.

Abstract

Nephrotoxicity remain a major life-threatening complication in cancer patients on cisplatin chemotherapy. In this study, we investigated the protective effect and possible cellular mechanism of the hesperetin, a naturally-occurring bioflavonoid against cisplatin-induced renal injury in rats. Hesperetin was administered at a dose of 50mg/kg and 100mg/kg orally for 10days and cisplatin (7.5mg/kg, ip) was administered on the 5th day of experiment. Cisplatin induced nephrotoxicity was evidenced by alteration in the level of markers such as blood urea nitrogen, creatinine, serum albumin and severe histopathological changes in kidney. Cisplatin administration also resulted in significant increase in the tissue oxidative stress and inflammatory cytokines. The level of antioxidants enzymes were decreased significantly in the cisplatin administered rats. Hesperetin treatment (50mg/kg and 100mg/kg) normalized the renal function by attenuation of the cisplatin-induced oxidative stress, lipid peroxidation, and inflammatory cytokines and histopathological alterations. On the basis of these experimental findings our present study postulate that co-administration of hesperetin with cisplatin chemotherapy may be promising preventive approach to limit the major mortal side effect of cisplatin.

摘要

顺铂化疗的癌症患者仍存在严重威胁生命的肾毒性并发症。在这项研究中,我们研究了桔皮素对顺铂诱导的大鼠肾损伤的保护作用及其可能的细胞机制。桔皮素以 50mg/kg 和 100mg/kg 的剂量口服给药 10 天,实验第 5 天给予顺铂(7.5mg/kg,ip)。顺铂引起的肾毒性表现为标志物水平的改变,如血尿素氮、肌酐、血清白蛋白和肾脏的严重组织病理学变化。顺铂给药还导致组织氧化应激和炎性细胞因子显著增加。顺铂给药大鼠的抗氧化酶水平显著降低。桔皮素治疗(50mg/kg 和 100mg/kg)通过减轻顺铂诱导的氧化应激、脂质过氧化和炎性细胞因子以及组织病理学改变来改善肾功能。基于这些实验结果,我们的研究提出,桔皮素与顺铂化疗联合应用可能是限制顺铂主要致命副作用的有前途的预防方法。

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