PMID: 8968373Dec 1, 1996Paper

Protection of acetaminophen-induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinate pretreatment

The Journal of Pharmacology and Experimental Therapeutics
Sidhartha D RayM W Fariss

Abstract

This study of acetaminophen (AAP) hepatotoxicity examined whether some aspects of the highly integrated process of drug-induced toxicity involves apoptosis, in addition to necrosis in vivo; and if so, whether cholesteryl hemisuccinate (CS) pretreatment would selectively interfere with apoptotic or necrotic liver cell death. We have previously demonstrated that CS preexposure in vivo, protects hepatocellular necrosis and necrosis-related events induced by carbon tetrachloride (CCl4) administration. Our study demonstrates that administration of hepatotoxic doses of AAP (350-500 mg/kg, i.p.) to ICR mice (CD-1) results in severe liver injury leading to cell death both by necrosis and apoptosis. AAP-induced cell death was preceded by massive elevation in serum alanine aminotransferase coupled with rapid loss of large genomic DNA (2-24 hr), fragmentation of DNA in the form of a ladder (2-24 hr), apoptotic nuclear condensation at early hours (2-6 hr) followed by massive fragmentation and margination of heterochromatin at later (6-24) hours and a near total loss of glycogen in pericentral areas. Although CS (100 mg/kg, i.p.) alone had no noticeable biochemical or morphological effects, its administration before AAP (350-500 mg/kg, i.p....Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis