Carbon tetrachloride–induced hepatic injury is associated with global DNA hypomethylation and homocysteinemia: Effect of S-adenosylmethionine treatment
✍ Scribed by Gregorio Varela-Moreiras; Elena Alonso-Aperte; Mireia Rubio; Marta Gasso; Ramón Deulofeu; Luis Alvarez; Juan Caballería; Juan Rodés; José M. Mato
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 761 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Carbon tetrachloride (CCl,) administration to rats produces hepatic cirrhosis and supplementation with S- adenosylmethionine (SAM) can partially prevent CCLinduced liver injury. These effects are thought to be caused by oxidative stress and the subsequent formation of free radicals, but the mechanism whereby this occurs and the accurate nature of the mechanisms by which SAM exerts its protective action are not well understood.
The effect of short-term administration of CCl, on hepatic DNA methylation and on S A M and S-adenosylhomocysteine (SAH) were assessed. CCl, administration to rats for 3 weeks resulted in hypomethylation of liver DNA, determined by comparing the extent to which DNA from livers of control or treated animals could be methylated in uitro using [3H-methyl] SAM as methyl donor. "his CCl, effect on DNA methylation was corrected by the administration of SAM (10 mgkgld, intramuscularly), with values of methyl groups incorporation comparable with those observed in the control animals. Hepatic SAM was decreased by CCl, (65.3 f 5.27 vs. 102.2 f 4.89 nmoVg; P < .05) and SAH was increased (69.5 f 14.6 vs. 29.4 f 3.83 nmoVg;P < .05). This led to a marked reduction of the S M S A H ratio (the methylation ratio) from 3.47 in control rats to 0.94 in CCL-treated animals (P < .05). SAM treatment partially prevented (P < .05) the reduction of the ratio S M S A H induced by CCL. CC4 also induced a marked elevation of serum homocysteine levels (more than 20-fold; P < .001), which was partially prevented by SAM administration. A decrease in serum methionine concentration was also observed (20.87 f 1.76 vs. 31.25 f 2.37 pmol/L; P < .05) in response to CCL, whereas cystathionine levels remained unchanged. Hepatic folate was reduced by CCl, (11.2 ? 2.1