RT Journal Article
SR Electronic
T1 Paradoxical effects of cobaltous chloride and salts of other divalent metals on tissue levels of reduced glutathione and microsomal mixed-function oxidase components.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 718
OP 724
VO 205
IS 3
A1 H A Sasame
A1 M R Boyd
YR 1978
UL http://jpet.aspetjournals.org/content/205/3/718.abstract
AB Treatment of animals with cobaltous chloride caused decreases in hepatic, pulmonary and renal cytochrome P-450, and alterations in levels of other components of microsomal mixed-function oxidases, which can alter the rate of biotransformation of certain drug substrates. The treatment also caused a striking, dose-dependent elevation in tissue levels of reduced glutathione (GSH), within 2 to 8 hours. The effect of cobalt on GSH occurred in all tested animal species and strains. Actinomycin-D partially prevented the cobalt-stimulated rise in hepatic GSH. Salts of several other divalent metals also produced sharply elevated levels of hepatic GSH, occurring concomitantly with decreased microsomal content of cytochrome P-450. These results suggest that pretreatment of animals with cobaltous chloride, or other divalent metal salts, could alter the disposition of certain toxic, alkylating drug metabolites not only by decreasing the rate of formation of the reactive metabolites, but also by increasing the amount of GSH available for the formation of their less reactive, less toxic, GSH conjugates.