Influence of Alpha-Ketoglutarate on Drosophila melanogaster Resistance to Different Toxicants

The fruit fly Drosophila melanogaster, a popular genetic model, has been used extensively in toxicological and nutritional research. Using D. melanogaster we have recently found the protective effects of alpha-ketoglutarate (AKG), an important intermediate of the Krebs cycle, against toxic effects of sodium nitroprusside and ethanol. The aim of this work was to investigate the ability of dietary alpha-ketoglutarate to alleviate developmental toxicity of some xenobiotics such as 2,4-dichlorphenoxyacetic acid (2,4-D), potassium dichromate, cumene hydroperoxide and aluminum chloride on D. melanogaster. Materials and methods. D. melanogaster Canton S strain was used in all experiments. Flies were cultivated on yeast-sucrose medium containing 5% pressed yeast, 5% sucrose, 1% agar, and 0.18 % nipagin. This medium was denoted as the control. Experimental media contained additionally 10 mM AKG, 5 mM 2,4-D, 1 mM K2Cr7O4, 1 mM cumene hydroperoxide, 10 mM AlCl3, and combinations of the indicated xenobiotics with 10 mM AKG. About 100 eggs were put in each 100 ml glass bottle with 15 ml of the experimental diets. The dynamics of flies development on different experimental diets was assessed by counting the number of pupae formed once per day, starting from 96 hours after egg deposition. Food intake was measured by indirect methods using FD&C Blue No. 1 dye. Locomotor activity of adult flies was assessed by climbing activity assay. Results. The pupation rate and total number of pupae formed were significantly lower on the food containing 5 mM 2,4-dichlophenociacetic acid, 10 mM AlCI3, 1 mM K2Cr2O7 and 1 mM cumene hydroperoxide. Food supplementation with 10 mM AKG alleviated toxic effects of the xenobiotics added to food, except cumene hydroperoxide, and improved D. melanogaster development. The latter was characterized by accelerating pupation time and increase in total pupae formed. The presence of 10 mM AlCl3 in the food did not affect food intake by larvae, but larvae consumed more food, containing mixture “AlCl3 and AKG” as compared to control ones. Two-day-old flies reared on AlCl3-supplemented food had lower climbing activity than control ones. At the same time, flies reared on food containing AlCl3 and AKG did not differ from the controls in climbing activity. Conclusions. The obtained results indicate that supplementation of food with alpha-ketoglutarate alleviates developmental toxicity of certain xenobiotics and improves the physiological state of young D. melanogaster flies, reared on food containing these toxicants. The detailed mechanisms of protective effects of AKG are directions for future research.