In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.
Troglitazone (TRO), a member of the thiazolidinedione class of drugs, has been associated with hepatotoxicity in patients. The following in vitro study was conducted to investigate the effects of TRO on mitochondrial function and viability in a human hepatoma cell line, HepG2. TRO induced a concentration- and time-dependent increase in cell death, as measured by lactate dehydrogenase release. Exposure to 50 or 100 micro M TRO produced total loss of cell viability within 5 h. Preincubation of HepG2 cells with P450 inhibitors did not significantly protect against TRO-induced cell death suggesting that P450 metabolism was not required to induce cell death. Preincubation with the mitochondrial permeability transition inhibitor, cyclosporin A, provided complete protection against TRO-induced cell death. Our results also indicated that TRO produced concentration-dependent decreases in cellular ATP levels and mitochondrial membrane potential (MMP). Ultrastructural analysis demonstrated that TRO induced mitochondrial changes at concentrations of > or =10 micro M after 2 h. Decreased MMP and altered mitochondrial morphology occurred at time points that preceded cell death and at sublethal concentrations of TRO. These observations in HepG2 cells suggest that TRO disrupts mitochondrial function, leading to mitochondrial permeability transition and cell death.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.