The fenofibrate effect on genotoxicity in brain and liver and on the expression of genes regulating fatty acids metabolism of mice

Khorolskaya V.G.1 , Gureev A.P.1, Shaforostova E.A.1, Laver D.A.1, Popov V.N.2

1. Voronezh State University, Voronezh, Russia
2. Voronezh State University, Voronezh, Russia; Voronezh State University of Engineering Technologies, Voronezh, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20196505388      PubMed Id: 31666411
Year: 2019  Volume: 65  Issue: 5  Pages: 388-397
Fibrates are well-known agonists of the PPAR family (peroxisome proliferator-activated receptors). This class of drugs is used for the treatment of dyslipidemia and atherosclerosis. Fenofibrate is one of the members of this class of synthetic PPARα receptor ligands. The oral administration of 0.3% fenofibrate caused a decrease in strength due to loss of body weight in laboratory animals when improving behavioural features. Analysis of the mitochondrial DNA of liver cells showed a genotoxic effect of fenofibrate, due to accumulation of reactive oxygen species, which could be attributed to activation of peroxisomal β-oxidation processes, as well as to the lack of increase in the expression of genes encoding antioxidant defense proteins. Treatment with fenofibrate did not cause brain mtDNA damage. It has been shown that fenofibrate induced mitochondrial β-oxidation in the brain, as indicated by the increased expression of the Acadm and Cpt1a and Ppargc1a and Ppara. The study found no effect of fenofibrate on the increase of mitochondrial biogenesis in brain and liver cells. Thus, we can conclude that fenofibrate significantly affects lipid metabolism in the liver and brain, but in the liver it is associated with an increase of oxidative stress, resulting in mtDNA oxidative damage. However, fenofibrate-induced increase in the expression of Ppargc1a is not associated with an increase of mitochondrial biogenesis. This is consistent with the recent suggestion that PGC-1α might not be a master regulator of mitochondrial biogenesis.
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Keywords: fenofibrate, liver, brain, genotoxicity, fatty acids, mitochondrial biogenesis

Khorolskaya, V. G., Gureev, A. P., Shaforostova, E. A., Laver, D. A., Popov, V. N. (2019). The fenofibrate effect on genotoxicity in brain and liver and on the expression of genes regulating fatty acids metabolism of mice. Biomeditsinskaya Khimiya, 65(5), 388-397.
This paper is also available as the English translation: 10.1134/S1990750820010084
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