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

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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: