Lylyk M. Protective action of alpha ketoglutarate in Drosophila melanogaster for exposure to xenobiotics

The dissertation is devoted to the study of the ability of dietary alpha-ketoglutarate to alleviate the toxic effects of a number of xenobiotics on the fruit fly Drosophila melanogaster. The protective action of AKG was assessed by evaluating the survival of insects and measuring parameters of pro-/antioxidant defence in flies under exposure to sodium nitroprusside (SNP), aluminum chloride, potassium dichromate, 2,4-dichlorophenoxyacetic acid (2,4-D), and cumene hydroperoxide. A common feature of the selected xenobiotics is their ability to induce the development of oxidative stress. On the other hand, AKG, as is known, can affect the redox status of cells; therefore, the reduction of the intensity of oxidative stress was considered as one of the potential mechanisms of protective action of AKG. To test this assumption, we measured a number of indicators that characterize the pro-/antioxidant status of flies, namely levels of products of lipid oxidation, activity of enzymes sensitive to oxidation, levels of thiol-containing componds and activities of antioxidant and associated enzymes. For the first time, it was shown that the addition of AKG in the form of its disodium salt solution to the fly basic food can weaken the toxic effects of SNP, K2Cr2O7, 2,4-D, and AlCl3 on the development of D. melanogaster larvae by reducing the pupation time of larvae and increasing by 16-30% the total number of pupae formed, depending on the xenobiotic used and the line of fruit flies. It was found that the protective effects of AKG against SNP, which has a short half-life, is not related to changing of levels of SNP decomposition products – nitric oxide and free iron ions. The toxic effects of SNP in fruit flies included a reduction in the amount of food consumed by a larvae of third stage and the development of oxidative stress in adults. It was found that the modulating effects of AKG upon SNP exposure were manifested in the prevention of a decrease in catalase activity and in a decrease in the levels of lipid peroxides to the level of the control group. Together, it indicates the antioxidant mechanism of the protective effect of AKG.