Melatonin treatment protects liver of Zucker rats after ischemia/reperfusion by diminishing oxidative stress and apoptosis

• Published in: European journal of pharmacology 2013-02, Vol.701 (1-3), p.185-193
• Main Authors: Kireev, Roman, Bitoun, Samuel, Cuesta, Sara, Tejerina, Alejandro, Ibarrola, Carolina, Moreno, Enrique, Vara, Elena, Tresguerres, Jesus A.F.
• Format: Article
• Language: English
• Subjects: adenosine triphosphate; Adenosine Triphosphate - metabolism; alanine transaminase; animal models; Animals; antioxidants; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; aspartate transaminase; Caspase 9 - metabolism; caspase-9; clinical trials; DNA fragmentation; DNA Fragmentation - drug effects; endothelial nitric oxide synthase; enzyme activity; fatty liver; Gene Expression Regulation, Enzymologic - drug effects; Glutathione Disulfide - metabolism; inducible nitric oxide synthase; ischemia; Ischemia/reperfusion; Lipid Peroxidation - drug effects; liver; Liver - drug effects; Liver - injuries; Liver - metabolism; Liver - pathology; liver function; liver transplant; Male; Melatonin; Melatonin - pharmacology; metabolites; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type III - genetics; nitrogen oxides; obesity; Oxidative stress; Oxidative Stress - drug effects; patients; pharmacology; Rats; Rats, Zucker; Reperfusion Injury - enzymology; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; reverse transcriptase polymerase chain reaction; Steatotic liver; Zucker rat
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.11.038

Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35min of warm hepatic ischemia and 36h of reperfusion. One experimental group remained untreated and 2 were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.