This study was performed to determine whether the severity of chronic alcohol toxicity is altered by age and duration of drinking. Alcohol as 35of calorie intake (ED treatment) was administered to Sprague-Dawley rats at predetermined ages beginning at 1, 6, 12, 18, 24 and 27 months for a duration of treatment varying from 1 to 3 months. The degree of injury was compared to controls (CD treatment) of comparable age and duration of treatment. ED was associated with significantly higher serum levels of AST, total bilirubin and alkaline phosphatase (P<0.0001 for each test) without detectable differences due to age and duration of treatment. Liver triglycerides (as a measure of alcoholic fatty steatosis) were significantly increased by ED (P<0.0001) and influenced by both age and duration of treatment The greatest toxicity was observed in young animals. ED treatment beginning at 1 month of age was associated with an AST level 69above CD and liver triglycerides 463above CD; beginning at 18 months of age, ED produced an increase of 24in AST and 175in liver triglycerides. The heparic regenerative capacity, as measured by3H uptake into nuclear DNA, was similarly affected by both ED and age. Regeneration was significantly higher in youth. ED produced a 62increase above CD at 1 month compared to an 11increase beginning at 18 months of age. These observations suggest that juveniles develop more severe injury from alcohol but that a greater regenerative capacity exists in youth. This may explain the observed clinical relationship between age and prognosis seen in patients with severe alcoholic liver injury.
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