Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467216666230125150112

Amal Hofni, Fares E M Ali, Ahmed R N Ibrahim, Esam M Aboubaker

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Abstract

Objective: Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy.

Methods: Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks.

Results: STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities.

Conclusion: The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

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百里醌对链脲佐菌素诱导的糖尿病肾病的肾保护作用:NOX2和Nrf2信号的作用

目的:糖尿病肾病是慢性未控制糖尿病不可避免的并发症。糖尿病肾病的发病机制是多因素的，开发有效的治疗方法仍有待阐明。本研究旨在探讨NOX2和Nrf2在百里醌(THQ)对链脲佐菌素(STZ)诱导的糖尿病肾病的保护机制中的作用。方法:大鼠注射STZ (55 mg/kg)诱导糖尿病。采用四氢大麻素(10 mg/kg/d)口服治疗糖尿病大鼠，连续8周。结果:stz治疗大鼠血清肌酐、血清尿素和肌酐清除率升高。肾脏异常与NADPH氧化酶异构体、NOX2蛋白表达和活性升高以及丙二醛(MDA)升高有关。肿瘤坏死因子-α (TNF-α)水平、一氧化氮(NO)生物利用度及转化生长因子-β (TGF)-β)均显著升高。另一方面，与对照组相比，糖尿病大鼠的核因子e2相关因子(Nrf2)蛋白表达显著降低。然而，THQ治疗显著逆转了这些改变，随后改善了肾功能和病理异常。结论:THQ通过调节Nrf2/NOX2信号通路，对stz诱导的糖尿病肾病具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.