Effect of melatoni̇n on cardi̇ac function in an experi̇mental model of sepsis induced by lipopolysaccharide in rats

This present study investigated the effect of melatonin, a pleitropic endogenous antioxidant agent, on sepsis induced cardiac dysfunction. Therefore, its effect on biochemical biomarkers at the molecular level and its contribution to antioxidant capacity were evaluated with ELISA. Langendorff isolated heart perfusion and isolated organ bath experimental setups were used to evaluate heart function. At septic rats the maximum/minimum value of the derivative of the left ventricular pressure time curve over time, which shows the contraction/relaxation capacity of the heart has been reduced. Coronary flow rate and the pressure developed by the left ventricle decreased significantly in septic animals. There was no improvement in these targeted parameters at the melatonin treated septic group. On the other hand, the results shows the changes according to the baseline of these parameters, change rate in the melatonin treated septic animals was significantly less than that of the septic animals. The response of septic atrium to isoproterenol was significantly increased compared to that of healthy tissue. This increased contraction response was found to be decreased at melatonin treated septic animals after 10-8 M isoproterenol presence at the organ bath. No significant difference was observed in other parameters in the isolated organ bath experiments. IL-1β, IL-6 and TNF-α levels, major biomarkers of sepsis, in heart, spleen, liver and serum were decreased significantly in melatonin treated septic group compared to septic group. IL-17 has been associated with cardiac dysfunction in previous studies and this study showed that its levels was increased significantly in the presence of LPS. For the first time in the literature this study has shown that melatonin blocked the increase of IL-17 levels induced by sepsis. In line with previous studies melatonin treatment increased antioxidant capacity and decreased oxidant load in all samples.