Protective effect of S-Adenosyl-L-Methionine in hepatic uroporphyria. Evaluation in an experimental model.

The potential use of S-adenosyl-L-methionine (SAMe) as therapy for human porphyria cutanea tarda was investigated in an experimental model of hepatic porphyria - that is, chronic treatment of female rats with 0.2% hexachlorobenzene (HCB) in the diet. Administration of SAMe (25 mg/kg subcutaneously twice daily) during the last 15 days of HCB administration halved porphyrin accumulation in the liver but did not alter HCB-induced massive inhibition of uroporphyrinogen decarboxylase. Equally unaffected were inhibition of glutathione peroxidase and stimulation of lipid peroxide formation induced by HCB. Hypothetically, the beneficial effect of SAMe on hepatic prophyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphat

Bile and biliary lipid secretion in rats with hexachlorobenzene-induced porphyria. Effect of S-Adenosyl-L-Methionine administration.

We investigated liver morphology and biliary function in vivo in rats made porphyric by hexachlorobenzene (HCB). In one group of HCB rats were also evaluated whether S-adenosyl-L-methionine (SAMe), administered during the last 15 days of HCB treatment, attenuated liver injury and the accumulation of porphyrins (HCB + SAMe group). In HCB rats we found: (a) a 100% increase in liver weight; (b) a 500-fold increase in total liver porphyrins (TLP); (c) significantly increase serum bilirubin and cholesterol levels; (d) unchanged total bile flow (TBF) but enhanced levels of the bile acid independent fraction (BAIF); and (e) decreased excretion in bile of bile acids (BA), phospholipids (PL) and cholesterol (CHO) (58, 65 and 47%, respectively, expressed as mmol/min per kg liver). SAMe was found to partially reverse HCB-related effects. TLP levels were about 65% lower in HCB + SAMe treated rats than in HCB rats. However, while SAMe restored bile CHO excretion to control values, it did not influence bile excretion of BA, PL, or BAIF. In conclusion, HCB-induced porphyria was characterized by a complex derangement of liver morphology and biliary function that was unrelated to the extent of porphyrin accumulation in the live