Melphalan induced germ cell toxicity and dose‐dependent effects of β‐aminoisobutyric acid in experimental rat model: Role of oxidative stress, inflammation and apoptosis

Author:

Panghal Archna1,Kumar Vinod12,Jena Gopabandhu1ORCID

Affiliation:

1. Dept. of Pharmacology and Toxicology Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research S.A.S Nagar Punjab India

2. Dept. of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research S.A.S Nagar Punjab India

Abstract

AbstractThe success of chemotherapy regimens has led to an increase in cancer survival rate over the last decades. Melphalan has been widely used for the treatment of several types of cancers despite its gonadotoxic effects. Due to its ability to cause mutations in the spermatogonial stem cells and spermatids, melphalan can exert a negative impact on male reproductive health in young cancer survivors. β‐aminoisobutyric acid (BAIBA), a myokine released by skeletal muscles, has been reported to have beneficial effects in diabetic nephropathy, cardiomyopathy and hepatic toxicity. However, the exact role of BAIBA in chemotherapy‐induced germ cell toxicity is still unexplored. The present study aims to determine the dose‐dependent (25, 50, and 100 mg/kg) effects of BAIBA on melphalan‐induced (1.5 mg/kg) germ cell toxicity in sprague−dawley (SD) rats. The evaluation parameters included quantification of oxidative stress biomarkers, sperm count, sperm motility and head morphology, sperm and testicular DNA damage, sperm mitochondrial membrane potential, ultrastructural changes in sperms, histological and protein expression studies in testes. Melphalan treatment significantly altered all the above‐mentioned parameters and the high dose (100 mg/kg) of BAIBA restored melphalan‐induced toxicity in a significant manner by exerting antioxidant, anti‐inflammatory and antiapoptotic effects. However, the medium dose (50 mg/kg) of BAIBA decreased the toxicity of melphalan and the low dose (25 mg/kg) of BAIBA failed to counteract the melphalan‐induced male germ cell toxicity as well as the peripheral blood micronucleus induction. The antioxidant, anti‐inflammatory and antiapoptotic role of BAIBA in melphalan‐induced gonadal damage is a novel finding in an experimental rat model.

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Toxicology,Molecular Biology,Molecular Medicine,Biochemistry,General Medicine

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3