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 F(2alpha) (8-iso-PGF(2alpha)), and 15-keto-13,14-dihydro-PGF(2alpha) (15-keto-PGF(2alpha)), 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(2alpha) and 15-keto-PGF(2alpha), did not activate HSCs, which were preactivated or not preactivated by TGF-beta1. Our results clearly indicate that LPO products, such as MDA, 8-iso-PGF(2alpha) and 15-keto-PGF(2alpha), cannot directly activate HSCs.
Fang
Hsun-Lang
HL
Graduate Institute of Chinese Pharmaceutical Science, College of Pharmacy, China Medical University, Taichung 404, Taiwan.
Lin
Wen-Chuan
WC
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D002470:Cell Survival; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003314:Corn Oil / Q000008:administration & dosage; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism / Q000494:pharmacology; D018613:Microscopy, Confocal; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D024042:Collagen Type I; D053773:Transforming Growth Factor beta1; C075750:8-epi-prostaglandin F2alpha; C026528:15-ketoprostaglandin F2alpha; D008315:Malondialdehyde; D003314:Corn Oil; D015237:Dinoprost; D002251:Carbon Tetrachloride; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline