RT Journal Article
SR Electronic
T1 The mechanisms of cobalt chloride-induced protection against acetaminophen hepatotoxicity.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 25
OP 33
VO 14
IS 1
A1 S A Roberts
A1 V F Price
A1 D J Jollow
YR 1986
UL http://dmd.aspetjournals.org/content/14/1/25.abstract
AB The mechanism by which cobalt chloride protects hamsters from acetaminophen-induced hepatotoxicity has been reexamined. In agreement with earlier studies, cobalt chloride treatment produced a 1.5-fold increase in hepatic glutathione levels and a decrease in the cytochrome P-450-dependent oxidative metabolism of acetaminophen. Cobalt chloride treatment also suppressed the sulfation while enhancing the glucuronidation of acetaminophen. The suppression of sulfation was most marked at low, non-hepatotoxic doses, whereas the enhancement of glucuronidation was greatest at higher hepatotoxic doses of acetaminophen. Collectively, the data suggest that the protective effect of cobalt chloride treatment on acetaminophen hepatotoxicity results from a combination of the suppression of the toxic pathway of cytochrome P-450 oxidation, an increase in the protective capacity of glutathione, and an enhancement of the nontoxic pathway of glucuronidation.