Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats

C. L. Miranda, M. C. Henderson, R. L. Reed, John A Schmitz, D. R. Buhler

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Abstract

The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 μmol/kg as ZnCl2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose-dependent increase in plasma GOT and GPT 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7-fold increase in plasma GOT and 12-fold increase in GPT after PA (120 mg/kg) were reduced in 2.4- and 2.1-fold, respectively, by Zn pretreatment. The PA-induced liver necrosis was either reduced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P-450 content, aminopyrine N-demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalJournal of Toxicology and Environmental Health
Volume9
Issue number3
StatePublished - 1982
Externally publishedYes

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Pyrrolizidine Alkaloids
Alkaloids
Zinc
Rats
Liver
Aspartate Aminotransferases
Alanine Transaminase
Senecio
Pyrroles
Metallothionein
Plasmas
Tanacetum
Aminopyrine N-Demethylase
Metabolites
Cytochrome P-450 Enzyme System
Necrosis
Enzymes

ASJC Scopus subject areas

  • Toxicology
  • Pollution

Cite this

Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats. / Miranda, C. L.; Henderson, M. C.; Reed, R. L.; Schmitz, John A; Buhler, D. R.

In: Journal of Toxicology and Environmental Health, Vol. 9, No. 3, 1982, p. 359-366.

Research output: Contribution to journalArticle

Miranda, C. L. ; Henderson, M. C. ; Reed, R. L. ; Schmitz, John A ; Buhler, D. R. / Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats. In: Journal of Toxicology and Environmental Health. 1982 ; Vol. 9, No. 3. pp. 359-366.
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