Back to Search
Start Over
Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines
- Source :
- The American Journal of Physiology. Dec, 2001, Vol. 281 Issue 6, pG1348, 9 p.
- Publication Year :
- 2001
-
Abstract
- Nanji, Amin A., Kalle Jokelainen, Maryam Fotouhinia, Amir Rahemtulla, Peter Thomas, George L. Tipoe, Grace L. Su, and Andrew J. Dannenberg. Increased severity of alcoholic liver injury in female rats: role of oxidatire stress, endotoxin, and chemokines. Am J Physiol Gastrointest Liver Physiol 281: G1348-G1356, 2002.--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 in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-KB (NF-[kappa]B) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-[alpha] (TNF-[alpha]), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-[kappa]B activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-[alpha] and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-[kappa]B activation and chemokine production, enhancing liver injury. TNF-[alpha] and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences. cytokines; cyclooxygenase-2; tumor necrosis factor-[alpha]
Details
- ISSN :
- 00029513
- Volume :
- 281
- Issue :
- 6
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.81596157