Lipid peroxidation products do not activate hepatic stellate cells

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 F2α (8-iso-PGF2α), and 15-keto-13,14-dihydro-PGF2α (15-keto-PGF2α), on the activation of hepatic stellate cells (HSCs) in vivo and in vitro. Carbon tetrachloride (CCl4) was given orally to rats twice a week for 8 weeks. Corn oil was given daily to rats for 8 weeks. CCl4 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. CCl4 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-PGF2α and 15-keto-PGF2α, 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-PGF2α and 15-keto-PGF2α, cannot directly activate HSCs.