title: Lindane induces testicular apoptosis in adult Wistar rats through the involvement of Fas-FasL and mitochondria-dependent pathways.
abstract: Lindane, an organochlorine pesticide, is known to impair testicular functions and fertility. To elucidate the mechanism(s) underpinning the gonadal effects of lindane, we sought to investigate the levels of apoptosis-related proteins, namely cytochrome c, caspase-3 and-9, Fas and FasL in the testis of adult rats. Furthermore, the study aims to delineate whether nuclear factor kappa B (NF-kappaB) is involved in meditating the testicular effects of lindane. Animals were administered with a single dose of lindane (5mg/kg body weight) and sacrificed at specific post-treatment intervals (0, 3, 6, 12, 24 and 72h). Significant elevations in the levels of cytosolic cytochrome c with a parallel increase in pro-caspase-9 were observed as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL and caspase-3 were observed. Immunofluorescence studies revealed increased colocalization of Fas and caspase-3 in peritubular germ cells. FasL levels were increased in Sertoli and peritubular germ cells. The cytoplasmic levels of NF-kappaB p65 decreased from 3h following exposure with a maximal decline at 12 and 24h. Changes in the localization of NF-kappaB were observed with maximal nuclear translocation in germ cells at 12 and 24h. Terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) assay revealed a time-dependent increase in the number of apoptotic cells. Taken together, the data illustrate induction of testicular apoptosis in adult rats following exposure to a single dose of lindane. Early activation of NF-kappaB in contrast to late increase in Fas expression suggests a pro-apoptotic role of NF-kappaB in testicular response to lindane.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605 014, India.
authors.forename: B
authors.initials: B
authors.lastname: Saradha
authors.forename: S
authors.initials: S
authors.lastname: Vaithinathan
authors.forename: P P
authors.initials: PP
authors.lastname: Mathur
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053222:Fas Ligand Protein / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D053222:Fas Ligand Protein; D007306:Insecticides; D016328:NF-kappa B; D019014:fas Receptor; D001556:Hexachlorocyclohexane; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9