Synthesis and effect of biguanide derivatives on biochemiluminescence and level of reduced glutathione in rat blood serum and brain under ischemia-reperfusion conditions

Abstract

We have studied the effect of the newly synthesized biguanides N-[amino(imino)methyl]morpholine-4carboximidamide (I) and N-[amino(imino)methyl]piperidine-1-carboximidamide (II) on biochemiluminescence (BCL) parameters including (i) lightsum (S) and maximum flash intensity (I max ), which characterize the level of free-radical processes, and (ii) the slope of the BCL kinetic curve (tan a 2 ), which characterizes general antioxidant activity, and on the reduced glutathione level in rats brain and blood serum under post-ischemic reperfusion conditions. It was found that the investigated parameters, which increased in response to the development of oxidative stress with brain pathology, changed toward normalization under the influence of the biguanides. A dose-dependent action of these substances has been established. The administration of I and II in 25 and 50 mg/kg led to the most pronounced decrease in the BCL parameters and reduced glutathione concentration while 12.5 and 75 mg/kg doses did not lead to significant changes in the studied parameters. The results show that biguanides introduced in certain doses can decrease the free-radical oxidation level and produce a neuroprotective effect.