Abstract
Cultured adult rat liver cells (non-induced) were exposed to two different concentrations (2 μg/ml and 4 μg/ml) of cocaine-HCl for 1–3 hours. Cocaine-treated rat liver cells showed a significant increase in manganese superoxide dismutase (Mn-SOD) activity with time. Coinciding the rise in Mn-SOD activity was the Mn-SOD mRNA transcript, which also demonstrated a time-dependent elevation in its level (p < 0.005). At the end of 1 and 3 hr. of cocaine exposure, the increase in Mn-SOD activity was 23% (p < 0.05) and 39% (p < 0.005), respectively. In contrast, activities of catalase (CAT) and glutathione peroxidase (GSH-px) were significantly diminished. Induction of Mn-SOD mRNA by cocaine (4 μg/ml) was inhibited by actinomycin D (4 μM), revealing that the up regulation of Mn-SOD involved transcriptional activation. The increase in Mn-SOD was accompanied by a decrease in liver cell integrity, indicated by increased lactate dehydrogenase (LDH) release by rat liver cells. These results suggest that antioxidant enzymes may play a critical role in cocaine-induced liver injury.
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