Abstract
Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.
Highlights
Seminiferous tubule of testis harbors large number of germ cells at different stages of development and maturation in the spermatogenic cycle
Our findings revealed that curcumin and resveratrol co-treatment significantly ameliorated the effect of B(a)P in sperm cells
Our results indicated the involvement of three major Mitogen Activated Protein Kinases (MAPKs) (ERK1/2, p38 MAPK and JNK1/2) with B(a)P exposure in testicular germ cells. p38 MAPK and JNKs are activated in response to a variety of environmental stresses and inflammatory signals and promote apoptosis and growth inhibition whereas ERK activation is associated with conflicting cellular responses ranging from proliferation and differentiation to apoptosis (Peyssonnaux and Eychene, 2001; Djeu et al, 2002; Lee and McCubrey, 2002)
Summary
Seminiferous tubule of testis harbors large number of germ cells at different stages of development and maturation in the spermatogenic cycle These spermatogenic cells give rise to mature spermatozoa which are released into the tubular lumen as functional sperms by the process of spermatogenesis. The signaling events leading to germ cell apoptosis can be divided into two major pathways involving either mitochondria (intrinsic) or death receptors (extrinsic). The studies related to the germ cell apoptosis by environmental toxicants demonstrated the involvement of both the mitochondria dependent; intrinsic and death receptor dependent; extrinsic apoptotic pathways. The pro-apoptotic family members like Bax and Bak induce permeabilization of the outer mitochondrial membrane that leads to the release of cytochrome c. Cytochrome c activates activator caspase 9 which further activates executioner caspases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
