Differential modulation of apoptotic gene expression by N-acetyl-l-cysteine in Leydig cells stimulated persistently with hCG in vivo

The present study was designed to investigate the molecular mechanisms of NAC (150 mg/kg bw twice/week) action in vivo under repeated hCG (100 IU/rat/day) stimulation to adult rats. Leydig cell refractoriness led to a significant decline in serum testosterone and intracellular cAMP by day 30 of chronic hCG intervention which improved significantly following NAC co-administration. It inhibited the rise in lipid peroxidation, improved the activity of antioxidant enzymes along with intracellular glutathione and total antioxidant capacity in the target cells. Leydig cell apoptosis declined significantly (P < 0.001) with down-regulation of upstream, Fas, FasL, caspase-8, Bax and caspase-9, JNK/pJNK and downstream caspase-3 and PARP. On the other hand, anti-apoptotic Bcl2, NF-kβ, and Akt were up-regulated. Taken together, the above findings indicate that the specificity of NAC action was not restricted to regulating marker proteins in the extrinsic and JNK pathways as seen in vitro but extended to include intrinsic pathway of metazoan apoptosis as well.

► Study was designed to investigate the molecular mechanisms of NAC action in vivo under repeated hCG stimulation.
► Inhibited rise in Leydig cell lipid peroxidation, improved intracellular glutathione and activity of antioxidant enzymes.
► Facilitated better Leydig cell survival with down-regulation of upstream, and downstream apoptotic marker proteins.
► The findings conclude that the specificity of NAC action extends to regulate multiple pathways of metazoan apoptosis.