Resveratrol ameliorates benzo(a)pyrene-induced testicular dysfunction and apoptosis: Involvement of p38 MAPK/ATF2/iNOS signaling | Health & Environmental Research Online (HERO)

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Citation
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HERO ID

3378314

Reference Type

Journal Article

Title

Resveratrol ameliorates benzo(a)pyrene-induced testicular dysfunction and apoptosis: Involvement of p38 MAPK/ATF2/iNOS signaling

Author(s)

Banerjee, B; Nandi, P; Chakraborty, S; Raha, S; Sen, PC; Jana, K

Year

2016

Is Peer Reviewed?

Yes

Journal

Journal of Nutritional Biochemistry
ISSN: 0955-2863
EISSN: 1873-4847

Publisher

ELSEVIER SCIENCE INC

Location

NEW YORK

Volume

Page Numbers

17-29

Language

English

PMID

27162022

DOI

10.1016/j.jnutbio.2016.04.003

Web of Science Id

WOS:000380421700003

URL

https://linkinghub.elsevier.com/retrieve/pii/S0955286316300481
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Abstract

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3βHSD, 17βHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol also significantly decreased the B(a)P-induced AhR protein level, its nuclear translocation and subsequent promoter activation, thereby decreased the expression of CYP1A1. Resveratrol also down-regulated B(a)P-induced testicular iNOS production through suppressing the activation of p38 MAPK and ATF2, thus improved the oxidative status of the testis and prevented apoptosis. Our findings cumulatively suggest that resveratrol inhibits conversion of B(a)P into BPDE by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords

Apoptosis; ATF2; B(a)P; INOS; P38 MAPK; ROS; Testis