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黄嘌呤衍生物对三氧化二砷诱导的小鼠肝、肾组织氧化应激的保护作用。

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.

机构信息

Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Drug Res (Stuttg). 2024 Mar;74(3):133-144. doi: 10.1055/a-2247-5232. Epub 2024 Feb 13.

Abstract

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

摘要

在这项研究中,我们研究了黄嘌呤衍生物己酮可可碱(PTX)作为一种保护剂,对三氧化二砷(ATO)诱导的小鼠肝肾损伤的保护作用。将 36 只小鼠分为六组,分别腹腔注射生理盐水、ATO、PTX 或联合用药,持续四周。采集血样进行血清生化分析,同时对肝组织进行组织病理学检查,并通过 Real-Time PCR 评估氧化应激标志物和抗氧化基因的表达。ATO 暴露显著增加了血清标志物(肌酐、ALT、BUN、ALP、AST),并诱导了肝组织的病理变化。此外,它还增加了肾和肝的一氧化氮(NO)和脂质过氧化(LPO)水平,降低了抗氧化酶的表达(CAT、GSR、GPx、MPO、SOD)、总巯基(TTGs)和总抗氧化能力(TAC)。相反,PTX 治疗可有效降低血清肝、肾标志物,改善抗氧化标志物,并诱导组织病理学改变。值得注意的是,PTX 对肾和肝的 NO 水平没有显著影响。这些发现表明,PTX 具有减轻各种损伤(包括暴露于 ATO)引起的肝和急性肾损伤的治疗潜力。

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