Comparison of the effects of ascorbyl palmitate and L-ascorbic acid on paracetamol-induced hepatotoxicity in the mouse.

Abstract:

:The effects of ascorbyl palmitate (ASCP) and free L-ascorbic acid (LAA) on the hepatotoxicity of paracetamol (acetaminophen) and the in vivo covalent binding of reactive paracetamol metabolites to hepatic proteins has been studied in male MF1 mice. The oral administration of [3H(G)]paracetamol (600 mg/kg) resulted in covalent binding to hepatic proteins, a depletion of hepatic non-protein sulphydryl (NPS) groups after 2 h, and a marked elevation of plasma alanine aminotransferase (ALAT) activity after 24 h. The co-administration of paracetamol and ASCP (1412 mg/kg, equivalent to 600 mg/kg free LAA), but not paracetamol and LAA (600 mg/kg), significantly reduced covalent binding of paracetamol metabolites at 2 and 4 h after treatment. In addition ASCP, but not LAA, significantly reduced the depletion of NPS groups and the elevation of plasma ALAT activity. ASCP also completely prevented the 35% mortality observed at 24 h in paracetamol treated mice. These results demonstrate that ASCP, but not LAA, when co-administered orally with the analgesic is an effective inhibitor of paracetamol-induced hepatotoxicity in the mouse. The mechanism by which ASCP prevents liver injury appears to involve destruction of reactive paracetamol metabolites which is associated with a sparing action on hepatic reduced glutathione levels.

journal_name

Toxicology

journal_title

Toxicology

authors

Jonker D,Lee VS,Hargreaves RJ,Lake BG

doi

10.1016/0300-483x(88)90133-3

subject

Has Abstract

pub_date

1988-11-30 00:00:00

pages

287-95

issue

3

eissn

0300-483X

issn

1879-3185

pii

0300-483X(88)90133-3

journal_volume

52

pub_type

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