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 porphyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphate.
Cantoni
L
L
Mario Negri Pharmacologic Research Institute and BioResearch S.p.A., Milan, Italy.
Budillon
G
G
Cuomo
R
R
Rodinò
S
S
Le Grazie
C
C
Di Padova
C
C
Rizzardini
M
M
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D005260:Female; D006581:Hexachlorobenzene; D008107:Liver Diseases / Q000188:drug therapy* / Q000201:enzymology; D011164:Porphyrias / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D011166:Porphyrins; D006581:Hexachlorobenzene; D012436:S-Adenosylmethionine; D014575:Uroporphyrinogen Decarboxylase