Cocaine-induced increase of Mn-SOD in adult rat liver cells.
Cultured adult rat liver cells (non-induced) were exposed to two different concentrations (2 microg/ml and 4 microg/ml) of cocaine-HCI 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 microg/ml) was inhibited by actinomycin D (4 microM), 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.
Devi
B G
BG
Research Institute on Addictions, Buffalo, New York 14203, USA. devi@ria.org
Chan
A W
AW
D000818:Animals; D015152:Blotting, Northern; D002374:Catalase / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003042:Cocaine