Cutaneous granulomatous lesions are usually present at the diagnosis of systemic sarcoidosis, and the type of cutaneous involvement may have prognostic significance.
Carbon tetrachloride (CCl,) administration to rats produces hepatic cirrhosis and supplementation with Sadenosylmethionine (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] Carbon tetrachloride (Cch), a toxic agent commonly used for the study of liver diseases in different experimental animal models, is a substrate for P-450 where it is converted to CC1, radicals, which generate CC1300 radicals by reacting with molecular oxygen. Because CC1, radicals react with membranes and induce lipid peroxidation, membrane damage by free radical chain reaction has been proposed as the major cause of hepatocellular injury by CC14, the probable initial event being mitochondria1 membrane injury. ' We have previously shown that administration of CCl, to rats for 3 weeks produces liver steatosis.' When CC14 administration was maintained for 6 additional weeks, the majority of the animals had developed cirrhosis. The later histological alterations were accompanied by a decrease of hepatic S-adenosylmethionine (SAM) synthetase activity and glutathione (GSH) depletion. ' The above results were partially corrected by the administration of exogenous SAM, but the mechanism whereby this occurs and the accurate nature of the mechanisms by which SAM exerts its protective action are not well understood. SAM serves as the donor of methyl groups in many transmethylation reactions (e.g., DNA-, phospholipid-, and protein-methylation).In donating its methyl group, SAM is converted to Sadenosylhomocysteine (SAH), which in turn is hydrolyzed to homocysteine and adenosine. Homocysteine can then be remethylated to methionine (via Blz-dependent methionine synthase or additionally in liver by betaine homocysteine methyltransferase) or degraded via the transsulphuration pathway. The transsulphuration pathway is the principal mechanism by 1310
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