Effects of daily, light and moderate-heavy ethanol exposure on extent of hepatic injury and recovery following toxin-induced acute hepatitis in rats.
Daily, light ethanol consumption enhances hepatic regeneration following 70% partial hepatectomy in rats. Whether such consumption has a beneficial effect on the outcome following toxin-induced acute hepatitis has yet to be determined. One hundred ten adult male Spragne-Dawlay rats (200-250 g) were randomized to receive daily gavages with ethanol 1.0 g/kg (light ethanol group), 3.0 g/kg (moderate-heavy ethanol group), or an equal volume of tap water (controls). On day 30, a single injection of D-galactosamine hydrochloride (1.0 g/kg) (D-gal), a potent hepatotoxin that induces liver failure within 24-48 hr, was administered intraperitoneally. Gavages were discontinued and rats killed (N = 4-6/group) on days 1, 3, 5, 7, and 10 after D-gal. Serum AST, bilirubin, and liver histology served to document the extent of liver injury and [3H] thymidine incorporation into hepatic DNA: hepatic regenerative activity. Compared to controls, peak serum AST levels were significantly decreased in the light (-40%, P < 0.05) and increased in the moderate-heavy (+32%, P < 0.05) ethanol groups. Serum bilirubin levels approximately doubled in the light ethanol group while increasing sixfold in the moderate-heavy and control groups (P < 0.05). Histologic evidence of hepatic injury (graded 0-IV) was limited in the light ethanol group, intermediate in controls, and most extensive in the moderate-heavy ethanol group (P < 0.05). Despite less hepatic injury, hepatic regeneration was similar in the light ethanol group compared to controls and significantly impaired in the moderate-heavy ethanol group (P < 0.01). In conclusion, the results of this study indicate that daily, light ethanol administration attenuates hepatic injury, improves hepatic function, and enhances hepatic regeneration following toxin-induced hepatitis in rats.
Zhang
Manna
M
Liver Diseases Unit, University of Manitoba, Winnipeg, Manitoba, Canada.
Uhanova
Julia
J
Corbin
Ian
I
Bernstein
Charles
C
Minuk
Gerald Y
GY
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000431:Ethanol / Q000494:pharmacology*; D005688:Galactosamine; D006505:Hepatitis / Q000473:pathology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
D000431:Ethanol; D005688:Galactosamine