Journal
TOXICOLOGY
Volume 255, Issue 3, Pages 131-139Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2008.10.016
Keywords
Lindane; Testis; Apoptosis; Fas/FasL system; Oxidative stress; Spermatogenesis
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Funding
- Indian Council of Medical Research, New Delhi, India
- Department of Science and Technology, Government of India [SP/SO/B-65/99, DST-FIST]
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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-kappa B) is involved in meditating the testicular effects of lindane. Animals were administered with a single dose of lindane (5 mg/kg body weight) and sacrificed at specific post-treatment intervals (0, 3, 6, 12. 24 and 72 h). Significant elevations in the levels of cytosolic cytochrome c with a parallel increase in pro-caspase-9 were observed Time-dependent elevations in the levels of Fas, FasL and caspase-3 as 6 h following exposure as early 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-kappa B p65 decreased from 3 h following exposure with a maximal decline at 12 and 24 h. Changes in the localization of NF-kappa B were observed with maximal nuclear translocation in germ cells at 12 and 24 h. 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-kappa B in contrast to late increase in Fas expression suggests a pro-apoptotic role of NF-kappa B in testicular response to lindane. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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