Caffeine protects against alcoholic liver injury by attenuating inflammatory response and oxidative stress
- 808 Downloads
Objective and design
The present investigation was designed to determine the effects of caffeine on alcohol-induced hepatic injury in mice.
Five groups of mice (8 each) were used.
The mice treated with different doses of caffeine (5, 10, and 20 mg/kg, respectively).
The degree of alcoholic liver injury was evaluated biochemically by measuring serum markers and pathological examination. Real time PCR and ELISA methods were used to check the expression of cytokines and CYP 450.
Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells. Interestingly, caffeine decreased hepatic mRNA expression of lipogenic genes, while it had no effect on protein expression of hepatic CYP2E1. Furthermore, caffeine decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation and inhibited the necrosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α), whereas Kupffer cells from caffeine treatment mice produced less ROS and TNF-α.
These findings suggest that caffeine may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress and inflammatory response.
KeywordsCaffeine Alcoholic liver injury Oxidative stress Inflammation
We gratefully acknowledge the support of this study by the grant from Anhui Provincial Natural Science Foundation (No 070413078) and the key Research Foundation of Higher Education of Anhui Province (No KJ2008A048) in China. We thank Dr. Hua Wang for critical reading of this manuscript.
- 7.O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol. 2010;105:14–32; quiz 33.Google Scholar
- 9.Nagy LE. Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Exp Biol Med (Maywood). 2003;228:882–90.Google Scholar
- 24.Modi AA, Feld JJ, Park Y, Kleiner DE, Everhart JE, Liang TJ, et al. Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology. 2009;51:201–9.Google Scholar
- 33.Gressner OA, Lahme B, Rehbein K, Siluschek M, Weiskirchen R, Gressner AM. Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPARgamma and SMAD2/3-dependent pathways. J Hepatol. 2008;49:758–67.CrossRefPubMedGoogle Scholar
- 37.Garcia-Ruiz C, Colell A, Morales A, Kaplowitz N, Fernandez-Checa JC. Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes. Mol Pharmacol. 1995;48:825–34.PubMedGoogle Scholar
- 42.Khanal T, Choi JH, Hwang YP, Jeong HG. Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice. Food Chem Toxicol. 2009;47(3):530–5.Google Scholar