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Obesity decreases hepatic glutathione concentrations and markedly potentiates allyl alcohol-induced periportal necrosis in the overfed rat.

Abstract
Liver biopsies from 9 out of every 10 obese individuals exhibit pathological changes of unknown aetiology and 3 out of every 10 reflect severe injury in the form of periportal fibrosis. To examine the hypothesis that excessive fibrosis in obesity arises in part from a predisposition to injury of the liver by drugs and xenobiotics, we administered 5, 10 and 25 mg/kg doses of the model periportal hepatotoxin, allyl alcohol, to obese Sprague-Dawley rats and age-matched non-obese controls. Alanine aminotransferase activity (ALT) in plasma was ten-fold more elevated in obese animals than in non-obese animals given the 25 mg/kg dose (P < 0.05). On fitting the ALT results to a non-linear, parametric model by iterative non-linear least squares regression, we found that the slope of the log dose ALT curve was similar for obese and non-obese rats. However, the minimum dose required to produce elevated ALT (DMIN) was 50% lower for obese animals (DMIN 6.47 +/- 2.75 vs. 13.3 +/- 0.96 mg allyl alcohol; P < 0.05). In a subsequent experiment, allyl alcohol was administered to obese rats based on ideal body weight, which is defined as the mean total body weight of an age-matched non-obese animal. With this dosing normalization, the 25 mg/kg ideal body weight doses translated to administration of a fixed dose of 13.5 mg allyl alcohol to obese rats. Obese rats treated in this fashion exhibited more severe necrosis in the periportal zone (median necrosis score 2 versus 0-1, P < 0.05) and increased mortality over controls (44% versus 0%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsD E Salazar, C L Sorge, S W Jordan, G B Corcoran
JournalInternational journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity (Int J Obes Relat Metab Disord) Vol. 18 Issue 1 Pg. 25-33 (Jan 1994) ENGLAND
PMID8130812 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Propanols
  • allyl alcohol
  • 1-Propanol
  • Alanine Transaminase
  • Glutathione
Topics
  • 1-Propanol (toxicity)
  • Alanine Transaminase (blood)
  • Animals
  • Glutathione (metabolism)
  • Liver (drug effects, metabolism, pathology)
  • Liver Cirrhosis, Experimental (chemically induced, etiology)
  • Male
  • Necrosis
  • Obesity (complications, metabolism)
  • Propanols
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

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