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

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 i...

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Main 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
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Redox Report
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2022.2116551
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author 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
author_facet 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
author_sort Fatma H. Rizk
collection DOAJ
description 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.
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spelling doaj.art-e483fe70de9d43b69d1fbb012bb690e32022-12-22T02:57:51ZengTaylor & Francis GroupRedox Report1351-00021743-29282022-12-0127117718510.1080/13510002.2022.2116551Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activationFatma H. Rizk0Nema A. Soliman1Suzan E. Abo-Elnasr2Heba A. Mahmoud3Muhammad T. Abdel Ghafar4Rasha A. Elkholy5Ola A. ELshora6Reham A. Mariah7Shaimaa Samir Amin Mashal8Amira A. El Saadany9Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Histology and Cell Biology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Pharmacology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, EgyptDepartment of Pharmacology, Faculty of Medicine, Tanta University, Tanta, EgyptObjectives 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.https://www.tandfonline.com/doi/10.1080/13510002.2022.2116551Monosodium glutamateoxidative stressfisetintesticular toxicitySIRT1NOX4
spellingShingle 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
Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
Redox Report
Monosodium glutamate
oxidative stress
fisetin
testicular toxicity
SIRT1
NOX4
title Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
title_full Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
title_fullStr Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
title_full_unstemmed Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
title_short Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation
title_sort fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving sirt1 activation
topic Monosodium glutamate
oxidative stress
fisetin
testicular toxicity
SIRT1
NOX4
url https://www.tandfonline.com/doi/10.1080/13510002.2022.2116551
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