Effect of kynurenic acid on enzymatic activity of the DNA base excision repair pathway in specific areas of the sheep brain

Relatively low levels of antioxidant enzymes coupled with high oxygen metabolism result in the formation of numerous oxidative DNA damages in the tissues of the central nervous system. Recently, kynurenic acid (KYNA), knowns for its neuroprotective properties, has gained increasing attention in this context. Therefore, the present study tested the hypothesis that increased KYNA levels in the brain would be able to positively influence mRNA expression of selected enzymes of the base excision repair pathway as well as enhance their efficiency in excising damaged nucleobases in specific areas of the sheep brain. The results revealed a significant increase in the relative mRNA abundance of N-methylpurine DNA glycosylase (MPG) following administration of both dose of KYNA across all examined tissues. The transcription of thymine-DNA glycosylase (TDG) increased significantly in all tissues in response to the lower KYNA dose compared to the control group. In addition, 8-oxoguanine (8-oxoG) DNA glycosylase (OGG1) mRNA levels were higher in both animal groups. Moreover, in the hypothalamus, hippocampus and amygdala, AP endonuclease 1 (APE1) mRNA expression increased under both doses of KYNA. In summary, the potential neuroprotective effects of KYNA in brain tissues may involve stimulation of BER pathways enzymes.