3,4-methylenedioxymethamphetamine ("Ecstasy") stimulates the expression of alpha1(I) procollagen mRNA in hepatic stellate cells.
3,4-Methylenedioxymethamphetamine, MDMA ("Ecstasy"), has been previously shown to produce cell necrosis and fibrosis in the liver. Our aim was to study the effect of MDMA on the type I collagen production by a cell line of hepatic stellate cells (HSC), the cell type mainly responsible for collagen synthesis in the liver. We demonstrated that MDMA increases alpha1(I) procollagen mRNA levels and that this increase correlates with glutathione depletion and enhanced hydrogen peroxide production by HSC. Pre-treatment with either glutathione monoethyl ester or deferoxamine prevents the MDMA-induced alpha1(I) procollagen mRNA expression, indicating oxidative stress to be a mediator of this effect. Lipid peroxidation was not detected in MDMA-treated cells and therefore does not seem to be involved in the pro-fibrogenic action of MDMA on HSC.
Varela-Rey
M
M
Department of Biochemistry, University of Navarra, Pamplona, Spain.
Montiel-Duarte
C
C
Beitia
G
G
Cenarruzabeitia
E
E
Iraburu
M J
MJ
D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018384:Oxidative Stress; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D011347:Procollagen; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D005978:Glutathione; D003676:Deferoxamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine