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

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-05-01 Epub Date: 2024-12-03 DOI:10.1007/s00210-024-03633-3
Nilgun Karasu, Mehmet Kuzucu, Ozge Cengiz Mat, Mustafa Gul, Arzu Yay, Munis Dundar
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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.

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去氧黄质对索拉非尼所致大鼠肝细胞癌模型肾毒性的保护作用。
索拉非尼是一种合成化合物和口服多药抑制剂,靶向生长信号和血管生成。它被广泛认为是晚期肝细胞癌(HCC)的标准治疗方法,但有毒副作用。Deinoxanthin是从耐辐射细菌Deinococcus radiodurans中纯化出来的,具有很强的抗氧化特性。本研究在大鼠肝细胞癌模型中研究了去氧黄质对索拉非尼肾毒性的保护作用。为此,我们检测了DDAH1、KIM1、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SOD、MDA、GST、CAT、TAS、TOS等各项参数进行了生化检测。测定肾组织BUN和肌酐水平。所有分析均采用RT-qPCR、Western blot和ELISA方法。结果表明,脱氧黄质具有较高的抗氧化能力,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氧黄质作为抗索拉非尼在HCC中肾毒性副作用的保护剂的潜力。我们的研究确定了索拉非尼和去氧黄质对肝细胞癌大鼠肾毒性的潜在协同作用。
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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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