ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 33 of 42
JMBS 2017, 2(4): 180–184

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

Lylyk M.P., Golovchak M.V., Shmihel H.V., Bayliak M.M.

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.

Keywords: alpha-ketoglutarate, Drosophila melanogaster, pupation, aluminum chloride, climbing activity

Full text: PDF (Ukr) 300K

  1. Lushchak V, Bahniukova T, Luzhna L. Pokaznyky oksydatyvnoho stresu. 2. Peroksydy lipidiv. Ukr biokhim zhurn. 2006; 6: 113-20. [Ukrainian]
  2. Rovenko BM. Obmezhennia vmistu vuhlevodiv u diieti lychynok sprychyniuie oksydatyvnyi stres u doroslykh komakh Drosophila melanogaster. Ukr. biokhim. zhurn. 2013; 8 5(5): 61-72. [Ukrainian]
  3. Abnoos Н, Fereidoni M, Mahdavi-shahri N, Haddad F, Jalal R. Developmental study of mercury effects on the fruit fly (Drosophila melanogaster). Interdiscip Toxicology. 2013; 6: 34-40.
  4. Amrani S, Rizki M, Creus A, Marcos R. Genotoxic Activity of Different Chromium Compounds in Larval Cells of Drosophila melanogaster, as Measured in the Wing Spot Test. Environmental and Molecular Mutagenesis. 1999; 34: 47-51.<47::AID-EM7>3.0.CO;2-B
  5. Atamaniuk T, Kubrak O, Storey K, Lushchak V. Oxidative stress as a mechanism for toxicity of 2,4 dichlorophenoxyacetic acid (2,4-D): studies with goldfish gills. Ecotoxicology. 2013; 22: 1498-508.
  6. Bayliak M, Shmihel H, Lylyk M, Storey KB, Lushchak VI. Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity. Alcohol. 2016; 55: 23-33.
  7. Bayliak M, Shmihel H, Lylyk M, Vytvytska OM, Storey JM, Storey KB, Lushchak VI. Alpha-ketoglutarate attenuates toxic effects of sodium nitrop1russide and hydrogen peroxide in Drosophila melanogaster. Environmental Toxicology and Pharmacology. 2015; 40: 650-9.
  8. Harrison AP, Pierzynowski SG. Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state of the art-review article. J Phisiol Pharmacol. 2008; 59: 91-106.
  9. Ihara S, Yoshikawa K, Touhara K. Chemosensory signals and their receptos in the olfactory neural system. Neuroscience. 2009; 254: 45-60.
  10. Jacob J. A study on food preference in Drosophila. The Scientia Review. 2009. е 234.
  11. Gospodaryov DV, Yurkevych IS, Jafari M, Lushchak VI, Lushchak OV. Lifespan extension and delay of age-related functional decline caused by Rhodiola rosea depends on dietary macronutrient balance. Longev Healthspan. 2013; 2 (1): 1-14.
  12. Grotewiel MS, Martin I, Bhandari P, Cook-Wiens E. Functional senescence in Drosophila melanogaster. Ageing Res Rev. 2005; 4 (3): 372-97.
  13. Kijak E, Rosato E, Knapczyk K, Pyza E. Drosophila melanogaster as a model system of aluminum toxicity and aging. Insect Sci. 2014; 21 (2): 189-202.
  14. Lushchak OV, Kubrak OI, Nykorak MZ, Storey KB, Lushchak VI. The effect of potassium dichromate on free radical processes in goldfish: Possible protective role of glutathione. Aquatic Toxicology. 2008; 87: 108-14.
  15. Perkhulyn NV, Rovenko BM, Zvarych TV, Lushchak OV, Storey JM, Storey KB, Lushchak VI. Sodium chromate demonstrates some insulin-mimetic properties in the fruit fly Drosophila melanogaster. Comp Biochem Physiol C Toxicol Pharmacol. 2015; 167: 74-80.
  16. Scorupa D, Dervisefendic A, Zwiener J, Pletcher SD. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell. 2008; 7: 478-90.
  17. Wu Z, Du Y, Xue H, Wu Y, Zhou B. Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production. Neurobiology of Aging. 2012 Jan; 33 (1): 199e1–199.e12.