Cerium oxide nanoparticles and metformin increase the reliability of the prooxidant/antioxidant balance and the survival of ageing rats

Abstract

In comparison with the action of metformin — mimetic of the calorie restricted diet, which prolong the animals lifespan, it has been studied the effect of nanoparticles of cerium dioxide (CeO2 NPs (1-2 nm)) on survival, physiological indices (the concentration of thyroxine, rectal temperature), as well as biochemical indices (content of lipid hydroperoxides, aconitase, glutathione peroxidase, glutaredoxin, glutathione reductase, NADP+ -dehydrogenase activities (glucose-6-phosphate-, malate- and isocitrate dehydrogenase)) in serum, liver mitochondrial and postmitochondrial fraction of ageing rats. It has been found that the prolonged use of CeO2 NPs with drinking water (0.25-0.30 mg/kg of body weight per day) and metformin (100-110 mg/kg of body weight per day) from 670 days after the birth lead to a significant increase in survival (the median survival of control rats was 900, in animals treated with CeO2 NPs — 960, and metformin — 990 days), a decrease in rectal temperature, a slowdown in the decrease in the level of thyroxine in blood, and normalization of the prooxidant/antioxidant balance in liver and blood tissues. Calculated integral index of reliability of prooxidant-antioxidant balance (reliability coefficient) in the studied tissues of rats in response to the application of the CeO2 NPs increased 4.99 times, and metformin — 4.94 times compared to intact animals. The data obtained allow us concluding about the prospects of the CeO2 NPs, as well as metformin for the development of geroprotector drugs, increasing the healthspan and survival of an ageing organism.