Metformin with propofol enhances the scavenging ability of free radicals and inhibits lipid peroxidation in mice.

Abstract

The aim of this study was to investigate the effects of metformin on anesthetic effect and anti-oxidative capacity in mice anesthetized with propofol. A total of 150 C57BL/6 mice were randomly assigned into the compatibility of an equivalent threshold dose of metformin with propofol group, and compatibility of different doses of metformin with 80 mg/kg propofol group, with 10 subgroups and 15 mice in each. Metformin and propofol were intraperitoneally injected in mice. The induction time of anesthesia in each mouse was recorded. 1 min after the disappearance of righting reflex, serum samples, and brain tissues were harvested, respectively. Subsequently, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) in serum and brain homogenate of each group were measured. Furthermore, the protein expressions of nuclear factor-kappaB (NF-κB) and Nuclear erythroid 2-related factor 2 (Nrf2) were analyzed by Western blot. Metformin supplementation did not influence the induction time of propofol anesthesia in mice, while the dose of propofol was significantly decreased. Besides, no significant correlation was found between an-esthesia induction time and the dose of metformin. Meanwhile, a certain dose of metformin could markedly increase the SOD activity in mouse brain tissues, whereas it could decrease the serum levels of MDA and LDH. In addition, metformin could remarkably inhibit the NF-κB activity and promote the Nrf2 expression. Metformin improves the anesthetic effect of a single dose or continuous intraperitoneal injection of propofol in mice. The compatibility of a certain dose of metformin with propofol can enhance the scavenging ability of free radicals and their metabolites. Furthermore, this inhibits lipid peroxidation in mice via NF-κB inhibition and Nrf2 activation.