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 as 35% of 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 69% above CD and liver triglycerides 463% above CD; beginning at 18 months of age, ED produced an increase of 24% in AST and 175% in liver triglycerides. The hepatic regenerative capacity, as measured by 3H-thymidine uptake into nuclear DNA, was similarly affected by both ED and age. Regeneration was significantly higher in youth. ED produced a 62% increase above CD at 1 month compared to an 11% increase 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.
Mendenhall
C L
CL
Veterans Administration Medical Center, Cincinnati, OH 45220.
Rouster
S D
SD
Grossman
C J
CJ
Roselle
G A
GA
Ghosn
S
S
Gartside
P
P
D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D001663:Bilirubin / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D002149:Energy Intake; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000737:chemistry / Q000378:metabolism
D014280:Triglycerides; D000431:Ethanol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin