Stimulation of microsomal spironolactone metabolism by reduced glutathione.

The first step in the conversion of spironolactone (SP) to its biologically active metabolites is deacetylation to 7 alpha-thiospirolactone (7 alpha-thio-SL). Studies were done to evaluate the effects of reduced glutathione (GSH) on SP deacetylation by adrenal microsomal preparations. In the absence of GSH, adrenal microsomes catalyzed the conversion of SP to 7 alpha-thio-SL at low rates.

Metabolic changes in alveolar type II cells after exposure to hydrogen peroxide.

Since oxygen metabolites may play an important role in pulmonary oxidant injury, the effects of hydrogen peroxide (H2O2) on energy metabolism in alveolar type II cells isolated from rats were studied. The major effect of H2O2 is a rapid and dramatic reduction in the steady-state level of cellular ATP; e.g.

Reaction of glutathione with a free radical metabolite of carbon tetrachloride.

Carbon tetrachloride and bromotrichloromethane are both metabolized by cytochrome P-450 in the presence of phenyl-N-t-butyl nitrone PBN) to the PBN/trichloromethyl (PBN/.CCl3) and the PBN carbon dioxide anion (PBN/.CO2-) radical adducts in the liver.

Inhibition of adrenocortical, mitochondrial and microsomal monooxygenases by SU-10'603, a steroid 17 alpha-hydroxylase inhibitor.

SU-10'603 is a pyridine derivative that is widely used as a steroid 17 alpha-hydroxylase inhibitor. Studies were done to evaluate its effects in vitro on several other monooxygenases in guinea pig adrenal mitochondrial and microsomal preparations. In adrenal mitochondria, SU-10'603 produced a concentration-dependent inhibition of 11 beta-hydroxylation; 50% inhibition was obtained at a concentration of approximately 0.

Carbon tetrachloride inhibits synthesis of pulmonary surfactant disaturated phosphatidylcholines and ATP production in alveolar type II cells.

Other studies have shown that inhalation of carbon tetrachloride (CCl4) decreases the amount of pulmonary surfactant lining the alveolar surface. Therefore, we studied the effects of CCl4 on the synthesis of surfactant phosphatidylcholines (PCs) in rat alveolar type II cells in vitro. The rate of incorporation of choline, palmitate or glycerol into disaturated PC (DSPC) is decreased in a concentration-dependent manner.