{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:33:53Z","timestamp":1771655633348,"version":"3.50.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:p> To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male 129\/SvJ mice (wild-type, WT) and glutathione S-transferase A4\u20134-null (GSTA4\u2212\/\u2212) mice for 40 days. GSTA4\u2212\/\u2212 mice were crossed with peroxisome proliferator-activated receptor-\u03b1-null mice (PPAR-\u03b1\u2212\/\u2212), and the effects of EtOH in the resulting double knockout (dKO) mice were compared with the other strains. EtOH increased lipid peroxidation in all except WT mice ( P &lt; 0.05). Increased steatosis and mRNA expression of the inflammatory markers CXCL2, tumor necrosis factor-\u03b1 (TNF-\u03b1), and \u03b1-smooth muscle actin (\u03b1-SMA) were observed in EtOH GSTA4\u2212\/\u2212 compared with EtOH WT mice ( P &lt; 0.05). EtOH PPAR-\u03b1\u2212\/\u2212 mice had increased steatosis, serum alanine aminotransferase (ALT), and hepatic CD3+ T cell populations and elevated mRNA encoding CD14, CXCL2, TNF-\u03b1, IL-6, CD138, transforming growth factor-\u03b2, platelet-derived growth factor receptor-\u03b2 (PDGFR-\u03b2), matrix metalloproteinase (MMP)-9, MMP-13, \u03b1-SMA, and collagen type 1 compared with EtOH WT mice. EtOH-fed dKO mice displayed elevation of periportal hepatic 4-hydroxynonenal adducts and serum antibodies against malondialdehyde adducts compared with EtOH feeding of GSTA4\u2212\/\u2212, PPAR-\u03b1\u2212\/\u2212, and WT mice ( P &lt; 0.05). ALT was higher in EtOH dKO mice compared with all other groups ( P &lt; 0.001). EtOH-fed dKO mice displayed elevated mRNAs for TNF-\u03b1 and CD14, histological evidence of fibrosis, and increased PDGFR, MMP-9, and MMP-13 mRNAs compared with the EtOH GSTA4\u2212\/\u2212 or EtOH PPAR-\u03b1\u2212\/\u2212 genotype ( P &lt; 0.05). These findings demonstrate the central role lipid peroxidation plays in mediating progression of alcohol-induced necroinflammatory liver injury, stellate cell activation, matrix remodeling, and fibrosis. <\/jats:p>","DOI":"10.1152\/ajpgi.00154.2014","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T00:33:58Z","timestamp":1418344438000},"page":"G403-G415","source":"Crossref","is-referenced-by-count":24,"title":["Increased 4-hydroxynonenal protein adducts in male GSTA4\u20134\/PPAR-\u03b1 double knockout mice enhance injury during early stages of alcoholic liver disease"],"prefix":"10.1152","volume":"308","author":[{"given":"Martin J. 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