Immunochemical Comparison of 3′-Hydroxyacetanilide and Acetaminophen Binding in Mouse Liver

摘要: The hepatotoxicity of the analgesic acetaminophen is believed to be mediated by covalent binding critical proteins. Radiolabeled 3'-hydroxyacetanilide, a regioisomer acetaminophen, covalently binds proteins at levels similar those but without toxicity. Covalent has recently been detected Western blot 50-kDa microsomal protein that comigrated with CYP2E1 and was accompanied loss activity. However, radiolabel studies previously indicated significant amount lost during electrophoresis. In present study, 3'-hydroxyacetanilide immunohistochemically in liver using an anti-acetaminophen antiserum. 3'-Hydroxyacetanilide (1000 mg/kg, ip) administration mice resulted panlobular immunostaining liver, single layer hepatocytes surrounding central veins having greatest intensity staining. Staining most intense 1 hr somewhat decreased 3 6 hr. contrast, immunochemical staining (250 confined centrilobular hepatocytes, area ensuing necrosis. Cobaltous chloride pretreatment total following 3'-hydroxyacetanilide. inhibitor diallyl sulfide vein only. analysis also eliminated protein. These data are consistent part CYP2E1, binding, other P450 enzymes.