Nf Kappa B Inhibitor Attenuates Antioxidant Enzyme Activity: Effect Of Exercise Training

Abstract

Gene regulation of antioxidant enzymes is known to be regulated via redox-sensitive signal transduction pathways involving nuclear factor (NF) kappaB and mitogenactivated protein kinases (MAPK). PURPOSE: The goal of this study is to examine whether the pharmacological agent pyrolidine dithiocarbamate (PDTC), a known NF kappaB inhibitor, or propranolol (PL), a beta-adrenergic blocker, affect basal levels of antioxidant enzymes activity due to interference with their signaling. We also investigated whether exercise training would alter the potential effects of these drugs. METHODS: Female Sprague-Dawley rats were injected (i.p.) daily with either PDTC (50 mg/kg body wt, N=16), PL (30 mg/kg, N=16) or saline (S, N=16). Half of each treatment group of rats participated in an 8-wk treadmill training regimen at 26 m/min, 15% grade for 1 h/day, 5 d/wk (T), whereas the other half group remained untrained (C). Heart, liver, deep (DVL) and superficial (SVL) vastus lateralis, soleus and gastrocnemius (Gas) muscles were harvested 24 h after the last exercise bout. RESULTS: Superoxide dismutase activity did not alter with PDTC, PL, or T. Glutathione peroxidase activity was decreased in DVL, SVL and Gas (P<0.05) of PDTC-C vs. S-C rats, whereas T restored these changes. PDTC rats showed lower heart catalase activity (P<0.01) vs. C rats. Malodialdehyde content was increased (P<0.05) with PDTC in heart, liver and SVL of C, and T attenuated the effects. CONCLUSIONS: These data suggest that impaired NF kappaB signaling by PDTC can affect antioxidant enzyme expression, whereas chronic exercise may protect against the drug-induced adverse effects and oxidative stress.