Early inhibition of the Na+/K+-ATPase ion pump during acetaminophen-induced hepatotoxicity in rat.
The status of Na+ regulation was examined during early stages of alkylation insult to rat liver. Na+/K+-ATPase activity in plasma membranes declined by 52% within 3 hr of treatment with 850 mg/kg acetaminophen. This loss preceded the release of alanine aminotransferase (2880 +/- 1550 U/ml) and necrosis (2+) seen at 24 hr. Activities of 5'-nucleotidase and Mg2+-ATPase and recovery of plasma membranes were comparatively unchanged at 3 hr. Because damage to Na+/K+-ATPase appeared early in the pathogenesis of acetaminophen hepatotoxicity, loss of hepatocellular Na+ regulation could represent one of the critical molecular consequences of lethal alkylation by acetaminophen.
D015720:5'-Nucleotidase; D000082:Acetaminophen / Q000494:pharmacology / Q000633:toxicity*; D000478:Alkylation; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D056486:Chemical and Drug Induced Liver Injury; D007473:Ion Channels / Q000187:drug effects*; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology; D008297:Male; D009708:Nucleotidases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D007473:Ion Channels; D000082:Acetaminophen; D012964:Sodium; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase