THE IMPACT OF AGE ON ALCOHOL TOXICITY IN THE RAT

This study was performed to determine whether the severity of chronic alcohol toxicity is altered by age and duration of drinking. Alcohol a s 35% of calorie intake (ED treatment) was administered to Sprague-Daw ley rats at predetermined ages beginning at 1, 6, 12, 18, 24 and 27 mo nths for a duration of treatment varying from 1 to 3 months. The degre e 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 dura tion of treatment. Liver triglycerides (as a measure of alcoholic fatt y steatosis) were significantly increased by ED (P < 0.0001) and influ enced by both age and duration of treatment. The greatest toxicity was observed in young animals. ED treatment beginning at 1 month of age w as associated with an AST level 69% above CD and liver triglycerides 4 63% above CD; beginning at 18 months of age, ED produced an increase o f 24% in AST and 175% in liver triglycerides. The hepatic regenerative capacity, as measured by H-3-thymidine uptake into nuclear DNA, was s imilarly affected by both ED and age. Regeneration was significantly h igher in youth. ED produced a 62% increase above CD at 1 month compare d to an 11% increase beginning at 18 months of age. These observations suggest that juveniles develop more severe injury from alcohol but th at a greater regenerative capacity exists in youth. This may explain t he observed clinical relationship between age and prognosis seen in pa tients with severe alcoholic liver injury.