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虾青素对肝癌模型大鼠索拉非尼诱导的肾毒性的保护作用。

Protective effect of deinoxanthin in sorafenib-induced nephrotoxicity in rats with the hepatocellular carcinoma model.

作者信息

Karasu Nilgun, Kuzucu Mehmet, Mat Ozge Cengiz, Gul Mustafa, Yay Arzu, Dundar Munis

机构信息

Faculty of Medicine, Department of Medical Genetics, Erciyes University, Kayseri, Turkey.

Faculty of Medicine, Department of Medical Genetics, Uskudar University, Istanbul, Turkey.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5969-5988. doi: 10.1007/s00210-024-03633-3. Epub 2024 Dec 3.

Abstract

Sorafenib is a synthetic compound and an orally administered multichines inhibitor that targets growth signaling and angiogenesis. It is widely recognized as the standard of care for advanced hepatocellular carcinoma (HCC) but has toxic side effects. Deinoxanthin, purified from the radioresistant bacterium Deinococcus radiodurans, has strong antioxidant characteristics. In this study, the protective effect of deinoxanthin against sorafenib-induced nephrotoxicity was investigated in a rat model of hepatocellular carcinoma. In this regard, the expressions of DDAH1, KIM1, and INOS genes were examined, histopathological and immunohistochemical analyses were performed, and various parameters such as SOD, MDA, GST, CAT, TAS, and TOS were tested biochemically. BUN and creatinine levels were measured in renal tissues. RT-qPCR, Western blot, and ELISA methods were used for all these analyses. As a result, the analyses show that deinoxanthin, which has a high antioxidant capacity, reduces kidney injury and can be used as a protective agent. The primary objective of this study is to evaluate the potential of deinoxanthin as a protective agent against the nephrotoxic side effects of sorafenib in HCC. Our study identified the potential synergistic effects of sorafenib and deinoxanthin on nephrotoxicity in rats with hepatocellular carcinoma.

摘要

索拉非尼是一种合成化合物,是一种口服的多激酶抑制剂,可靶向生长信号传导和血管生成。它被广泛认为是晚期肝细胞癌(HCC)的标准治疗药物,但具有毒副作用。从耐辐射细菌耐辐射球菌中纯化得到的去甲黄质具有很强的抗氧化特性。在本研究中,在肝细胞癌大鼠模型中研究了去甲黄质对索拉非尼诱导的肾毒性的保护作用。在这方面,检测了DDAH1、KIM1和INOS基因的表达,进行了组织病理学和免疫组织化学分析,并对超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽S-转移酶(GST)、过氧化氢酶(CAT)、总抗氧化能力(TAS)和总氧化应激(TOS)等各种参数进行了生化检测。测量了肾组织中的血尿素氮(BUN)和肌酐水平。所有这些分析均采用逆转录定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法(Western blot)和酶联免疫吸附测定法(ELISA)。结果显示,具有高抗氧化能力的去甲黄质可减轻肾损伤,可作为一种保护剂。本研究的主要目的是评估去甲黄质作为一种保护剂对抗索拉非尼在肝细胞癌中引起的肾毒性副作用的潜力。我们的研究确定了索拉非尼和去甲黄质对肝细胞癌大鼠肾毒性的潜在协同作用。

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