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
{"title":"Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.","authors":"Eman Mohamed Fath, Hatem H Bakery, Ragab M El-Shawarby, Mohamed E S Abosalem, Samar S Ibrahim, Nesrine Ebrahim, Ahmed Medhat Hegazy","doi":"10.1007/s11419-024-00697-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Forensic Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11419-024-00697-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

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.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
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).
期刊最新文献
Death due to unrecognized intoxication of nifedipine in an adult. Elucidation of toxic effects of 1,2-diacetylbenzene: an in silico study Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC–MS/MS using standard addition method Development of a simple estimation method of serum caffeine concentration using a point-of-care test kit for urinary caffeine.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1