Lipid peroxidation products do not activate hepatic stellate cells

Abstract Lipid peroxidation (LPO) is known to be associated with liver fibrosis in chronic liver injury. However, direct effects of the products of LPO on liver fibrogenesis are still not clear. In this study, we examined the LPO products, such as malondiladehyde (MDA), 8- iso -prostaglandin F 2α (8- iso -PGF 2α ), and 15-keto-13,14-dihydro-PGF 2α (15-keto-PGF 2α ), on the activation of hepatic stellate cells (HSCs) in vivo and in vitro . Carbon tetrachloride (CCl 4 ) was given orally to rats twice a week for 8 weeks. Corn oil was given daily to rats for 8 weeks. CCl 4 induced both free-radical-medicated and cyclooxygenase-2-dependent LPO. Free radical-medicated LPO showed an increase with corn oil treatment, whereas no effect was reflected on COX-2-dependent LPO. CCl 4 induced liver fibrosis in rats, but no liver fibrosis was observed in rats treated with corn oil. In vitro studies demonstrated that MDA, 8- iso -PGF 2α and 15-keto-PGF 2α , did not activate HSCs, which were preactivated or not preactivated by TGF-β1. Our results clearly indicate that LPO products, such as MDA, 8- iso -PGF 2α and 15-keto-PGF 2α , cannot directly activate HSCs.