Early inhibition of the Na+/K+-ATPase ion pump during acetaminophen-induced hepatotoxicity in rat |
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Authors: | G B Corcoran S J Chung D E Salazar |
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Institution: | Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260. |
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Abstract: | 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. |
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