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...
Main Authors: | , , , , , , , , , |
---|---|
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 |
_version_ | 1811299577250185216 |
---|---|
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. |
first_indexed | 2024-04-13T06:37:55Z |
format | Article |
id | doaj.art-e483fe70de9d43b69d1fbb012bb690e3 |
institution | Directory Open Access Journal |
issn | 1351-0002 1743-2928 |
language | English |
last_indexed | 2024-04-13T06:37:55Z |
publishDate | 2022-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Redox Report |
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 |
work_keys_str_mv | AT fatmahrizk fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT nemaasoliman fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT suzaneaboelnasr fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT hebaamahmoud fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT muhammadtabdelghafar fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT rashaaelkholy fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT olaaelshora fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT rehamamariah fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT shaimaasamiraminmashal fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation AT amiraaelsaadany fisetinamelioratesoxidativeglutamatetesticulartoxicityinratsviacentralandperipheralmechanismsinvolvingsirt1activation |