S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon.
Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L-methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S-adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
Lieber
C S
CS
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, NY 10468.
Casini
A
A
DeCarli
L M
LM
Kim
C I
CI
Lowe
N
N
Sasaki
R
R
Leo
M A
MA
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001706:Biopsy; D005969:Glutamate Dehydrogenase / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000648:ultrastructure; D010215:Papio; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology*
D012436:S-Adenosylmethionine; D005969:Glutamate Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione