Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

Abstract

Purpose: In sepsis Reactive Oxygen Species (ROS) production and apoptosis are two physiopathological processes that are increased. Succinate is a Krebs cycle intermediate that is reduced in Complex II of the mitochondria. This work aims to determine if succinate administration to septic rats improves serum ROS levels and serum and tissue levels of apoptosis. Methods: Sepsis was induced with cecal ligation and puncture in 200gr Sprague Dawley rats. 4 groups were formed (control, succinate, sepsis, and sepsis + succinate). 5mml/kg of intraperitoneal succinate were administered to the succinate and sepsis + succinate groups 2 h before sepsis induction and 2 h before sample taking. ROS levels were measured with dichlorofluorescein-diacetate, and apoptosis was measured with a Caspase-3 ELISA kit. Results: There were significant differences in serum ROS levels between the control group and the sepsis group (P = 0.012), but there were no differences in serum Caspase-3 levels (P = 0.15). The succinate administration reduced serum ROS levels in the sepsis + succinate group compared with the sepsis group in a statistically significant way (P = 0.004), but it did not reduce serum Caspase-3 levels (P = 0.39). There were no differences between groups in kidney and liver Caspase-3 levels. There was no correlation between serum ROS levels and serum Caspase-3 levels. Conclusions: In this model, ROS levels were reduced with succinate infusion, but Caspase-3 levels were not. In addition, ROS levels and apoptosis levels are not correlated, which suggests that those processes occur at different times.