Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.

IF 2.8 4区 医学 Q2 TOXICOLOGY Forensic Toxicology Pub Date : 2024-08-08 DOI:10.1007/s11419-024-00697-x
Eman Mohamed Fath, Hatem H Bakery, Ragab M El-Shawarby, Mohamed E S Abosalem, Samar S Ibrahim, Nesrine Ebrahim, Ahmed Medhat Hegazy
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Abstract

Purpose: The goal of the current study was to clarify the potential molecular mechanism underlying the protective effects of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of the Kelch-like-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in minimizing the oxidative stress induced by diazinon (DZN).

Methods: Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4 weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests. Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and histopathological examination.

Results: SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of HO-1, a crucial target enzyme of Nrf2.

Conclusions: SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.

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水飞蓟素通过 Keap1-Nrf2/heme oxygenase-1 信号通路改善重氮农诱导的大鼠亚急性肾毒性
目的:本研究的目的是阐明服用水飞蓟素(SIL)对二嗪农诱导的亚急性肾毒性具有保护作用的潜在分子机制,特别强调Kelch样相关蛋白-1(Keap1)-核因子红细胞2相关因子2(Nrf2)-血红素加氧酶-1(HO-1)信号通路在最小化二嗪农(DZN)诱导的氧化应激中的作用:方法:将 30 只成年雄性 Wistar 大鼠随机分为五组。第 1 组(G1)在典型对照条件下饲养,每天一次胃内注射生理盐水,连续 4 周;第 2 组每天一次胃内注射橄榄油,连续 4 周;第 3 组每天一次胃内注射水飞蓟素,连续 4 周;第 4 组每天一次胃内注射二嗪农,连续 4 周。G5每天在重氮农I/G给药前1小时进行水飞蓟素I/G给药,为期4周。实验结束时收集血液样本,用于测定全血细胞计数和肾功能检测。收集肾脏标本用于评估氧化标志物、mRNA 基因表达、蛋白质标志物和组织病理学检查:结果:通过恢复尿素和肌酐水平以及氧化指标,SIL减轻了DZN引起的肾功能障碍。虽然 Keap-1 的表达也有所升高,但 Nrf2 的过表达也增强了 HO-1 的表达,而 HO-1 是 Nrf2 的一个重要靶酶:假设 SIL 有助于预防和治疗 DZN 引起的肾毒性。
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来源期刊
Forensic Toxicology
Forensic Toxicology TOXICOLOGY-
CiteScore
5.80
自引率
9.10%
发文量
40
审稿时长
3 months
期刊介绍: The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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