Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines

• DOI: 10.1152/ajpgi.2001.281.6.g1348
• Publication Date: 2017-12-24T16:00:37Z
• Authors: Amin A. Nanji; Kalle Jokelainen; Maryam Fotouhinia; Amir Rahemtulla; Peter Thomas; George L. Tipoe; Grace L. Su; Andrew J. Dannenberg
• Keywords: Male; Chemokine CXCL2; Wistar; 590; Weight Gain; 5. Gender equality; Tumor Necrosis Factor-alpha - genetics; Endotoxemia - physiopathology; Chemokine CCL2; Sex Characteristics; 0303 health sciences; Liver Diseases; Liver - chemistry - metabolism - pathology; Cytochrome P-450 CYP2E1; Ethanol - administration & dosage; Isoenzymes; Messenger - analysis; RNA, Messenger - analysis; Liver; Alcoholic - pathology - physiopathology; Female; Chemokines; Iron - metabolism; Chemokines - genetics - physiology; Iron; Chemokine CCL2 - genetics; 03 medical and health sciences; Fish Oils; Dietary Fats, Unsaturated; Isoenzymes - genetics; Animals; Prostaglandin-Endoperoxide Synthases - genetics; Rats, Wistar; Liver Diseases, Alcoholic; Ethanol; Membrane Proteins; Fish Oils - administration & dosage; NF-kappa B - metabolism; Dietary Fats; Endotoxemia; Rats; Endotoxins; Dietary Fats, Unsaturated - administration & dosage; Oxidative Stress; Unsaturated - administration & dosage; Cyclooxygenase 2; Liver Diseases, Alcoholic - pathology - physiopathology; Cytochrome P-450 CYP2E1 - metabolism; Cyclooxygenase 1; RNA; Lipid Peroxidation; Endotoxins - physiology

Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important alcoholic male rats were further upregulated female rats. Male age-matched (7/group) fed ethanol a diet containing fish oil 4 wk by intragastric infusion. Dextrose isocalorically replaced control We analyzed histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-κB (NF-κB) activation, mRNA levels of cyclooxygenase-1 (COX-1) COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2). Alcohol-induced was vs. Female had higher iron increased NF-κB activation upregulation chemokines MCP-1 MIP-2. CYP2E1 activity TNF-α COX-2 similar Remarkably, dextrose also showed inflammation. Our findings ethanol-fed suggest that endotoxemia peroxidation females stimulate chemokine production, enhancing injury. are probably causing but do not explain differences.