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S ‐Adenosyl‐L‐methionine attenuates alcohol‐induced liver injury in the baboon
Author(s) -
Lieber Charles S.,
Casini Alessandro,
Decarli Leonore M.,
Kim ChoIl,
Lowe Nancy,
Sasaki Rika,
Leo Maria A.
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840110203
Subject(s) - baboon , methionine , alcohol , liver injury , chemistry , pharmacology , medicine , biochemistry , amino acid
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 < 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 μmol/gm after ethanol vs. 4.87 ± 0.36 μmol/gm in controls) that was attenuated by S ‐adenosyl‐L‐methionine (3.89 ± 0.51 μmol/gm in S ‐adenosyl‐L‐methionine‐methanol vs. 5.22 ± 0.53 μmol/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 < 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 < 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 < 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. Succinate dehydrogenase activity was increased in liver homogenates of animals fed ethanol (81.4 ± 4.0 mU/mg protein vs. 55.4 ± 2.1 mU/mg in controls; p < 0.001), probably reflecting the increased mitochondrial mass. S ‐adenosyl‐L‐methionine decreased succinate dehydrogenase levels (66.7 ± 3.6 mU/mg protein in S ‐adenosyl‐L‐methionine‐ethanol group vs. 45.5 ± 2.2 mU/mg in S ‐adenosyl‐L‐methionine controls; p < 0.001). S ‐adenosyl‐L‐methionine supplementation also significantly lessened the ethanol‐induced increase of plasma AST. Thus long‐term ethanol intake is associated with hepatic S ‐adenosyl‐L‐methionine depletion, which can be corrected at least in part by S ‐adenosyl‐L‐methionine administration, resulting in an attenuation of some alcohol‐induced liver injury.