Dose-dependent anti-inflammatory effect of ketamine on liver ischemia-reperfusion injury

In clinical practices, liver ishemia-reperfusion injury is generally encountered in hemorrhagic shock, late stages of sepsis, liver transplantation, surgical intervention to major trauma and hepatic resection. Ketamine suppresses IL-6 and TNF-?, due to inhibition of NF-kB. Aim of this experimental study is the evaluation of anti-inflamatuar effects of different doses of ketamine applications in liver I-R injury.We were used 18 Wistard-Albino rats weigthing 150-200 gr in this study. After A. Hepatica propria was loose and suspended with clamp, ischemia for 30 minutes and reperfusion for 4 hours were applicated to the subjects in group 1 (n=6). 2.5 mg/kg Ketamine IM after ischemia for 30 minutes was given to the subjects in group 2 (n=6), and in the same period 10 mg/kg Ketamine IM was given to subjects in group 3 (n=6) and subsequently reperfusion was provided. Before and after ischemia, and after reperfusion, blood samples were taken from all subjects and MDA, AST, ALT, TNF-?, IL-6, IL-1ß and NO levels were measured. The obtained data were taken as mean ? SD. Repeated measurements of analysis of variance were made with Posthoc-Tukey HSD test((Significance for all comparisons was defined as p<0.05), and Wilcoxen test was used for evaluation of repeated measurements in the groups (Significance for all comparisons was defined as p<0.005).According to pre-ischemic levels, post-ischemic TNF- ? , IL-1 ß and IL-6 levels were seen significantly increased in all groups (p<0.05). TNF- ? , IL-1 ß and IL-6 levels were increased less in reperfusion period, when compared with groups I and II (p<0.005). Acording to pre-ischemic period, MDA, NO, AST and ALT levels were found increased in post-ischemic, reperfusion periods of all groups (p<0.005). In the same period, when MDA, NO, AST and ALT levels were investigated, these levels were found increased less in ketamine given groups, according to control group.Investigation with light microscope on low and high dose ketamine given rats?livers showed significantly less histopathologic injury after reperfusion (p<0.05).When liver Kupffer cells are activated, they cause release of a lot of cytokines. In our study, we concluded that dose-dependent manner applications of ketamine to the subject with liver ischemia-reperfusion injury showed anti-inflamatuar effect.Keyword: Ketamine, IL-1ß, IL-6 and TNF-?, Ischemia-reperfusion injury