3,4-methylenedioxymethamphetamine ("ecstasy") stimulates the expression ofalpha 1(I) procollagen mRNA in hepatic stellate cells

3,4-Methylenedioxymethamphetamine, MDMA ("Ecstasy"), has been previously sh own to produce cell necrosis and fibrosis in the liver. Our aim was to stud y the effect of MDMA on the type I collagen production by a cell line of he patic stellate cells (HSC), the cell type mainly responsible for collagen s ynthesis in the liver. We demonstrated that MDMA increases alpha 1(I) proco llagen mRNA levels and that this increase correlates with glutathione deple tion and enhanced hydrogen peroxide production by HSC. Pre-treatment with e ither glutathione monoethyl ester or deferoxamine prevents the MDMA-induced alpha 1(I) procollagen mRNA expression, indicating oxidative stress to be a mediator of this effect. Lipid peroxidation was not detected in MDMA-trea ted cells and therefore does not seem to be involved in the pro-fibrogenic action of MDMA on HSC. (C) 1999 Academic Press.