Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation.

IF 5.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2022-12-01 DOI:10.1080/13510002.2022.2116551

Fatma H Rizk, Nema A Soliman, Suzan E Abo-Elnasr, Heba A Mahmoud, Muhammad T Abdel Ghafar, Rasha A Elkholy, Ola A ELshora, Reham A Mariah, Shaimaa Samir Amin Mashal, Amira A El Saadany

{"title":"Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation.","authors":"Fatma H Rizk, Nema A Soliman, Suzan E Abo-Elnasr, Heba A Mahmoud, Muhammad T Abdel Ghafar, Rasha A Elkholy, Ola A ELshora, Reham A Mariah, Shaimaa Samir Amin Mashal, Amira A El Saadany","doi":"10.1080/13510002.2022.2116551","DOIUrl":null,"url":null,"abstract":"Objectives: This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect.Methods: Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT-PCR in testicular tissues.Results: After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count.Discussion: Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448439/pdf/","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Report","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/13510002.2022.2116551","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 5

Abstract

Objectives: This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect.

Methods: Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H₂O₂), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT-PCR in testicular tissues.

Results: After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H₂O₂, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count.

Discussion: Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility.

Abstract Image

查看原文本刊更多论文

非西汀通过涉及SIRT1激活的中枢和外周机制改善大鼠氧化谷氨酸睾丸毒性。

目的:本研究旨在评估非瑟酮对味精(MSG)诱导的睾丸毒性的潜在缓解作用，并探讨沉默交配型信息调控2同源物1 (SIRT1)在此作用中的可能参与。方法:将40只雄性大鼠分为正常对照组、非瑟酮组、味精组和非瑟酮+味精组。采用ELISA法检测血浆中睾酮、GnRH、FSH和LH水平，以及睾丸组织中SIRT1和磷酸化amp活化蛋白激酶(pAMPK)水平。采用比色法检测过氧化氢(H2O2)、一氧化氮(NO)和还原性谷胱甘肽(GSH)， RT-PCR相对定量检测烟酰胺腺嘌呤二核苷酸磷酸氧化酶4 (NOX4)在睾丸组织中的表达。结果:30天后，非瑟酮可通过中枢作用于下丘脑-垂体-性腺轴，提高血浆GnRH、FSH、LH和睾酮水平，改善msg诱导的睾丸毒性。非瑟酮对睾丸的外周作用是增加睾丸SIRT1和pAMPK。此外，它通过显著降低H2O2、NO和NOX4的相对表达，同时显著增加降低的GSH水平，拮抗谷氨酸诱导的氧化应激。它还改善了精管的结构，减少了精子异常，增加了精子数量。讨论:非西汀通过中枢和外周机制改善msg诱导的睾丸毒性，使其成为男性不育症的有希望的治疗靶点。

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分钟内获得全文求助全文

来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.