Skip to main content
SpringerLink
Log in

Radioprotective role of uric acid: evidence from studies in Drosophila and human dermal fibroblast cells

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Exposure to ionizing radiation (IR) is a common phenomenon during medical diagnosis and treatment. IRs are deleterious because cellular exposure to IR can cause a series of molecular events that may lead to oxidative stress and macromolecular damage. Radiation protection is therefore essential and significant for improving safety during these procedures. Over decades several antioxidant molecules have been screened to explore their potential as radio-protectors with little success. Therefore, the current study was carried out to confirm the role of uric acid (UA)—a putative antioxidant molecule in radioprotection using radio-resistant insect Drosophila and human dermal fibroblast (HDF) cells. Here, we demonstrate the depleted levels of UA in the mutant flies of Drosophila melanogaster-rosy and by targeting xanthine oxidase (XO an enzyme involved in UA metabolism), through maintaining flies on an allopurinol mixed diet. Allopurinol is a drug that reduces UA levels by inhibiting XO; it reduces the survival percentage in D. melanogaster compared to wild type flies following gamma irradiation at a dose of 1000 Gy. Enzymatic antioxidants such as superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx) and levels of non-enzymatic antioxidants were measured to evaluate the importance of UA. The results indicate that lack of UA reduces the total antioxidant capacity. The activity of SOD was lowered in male flies. Furthermore, we show that supplementation of UA to HDFs cells in media improved their survival rate following gamma irradiation (2 Gy). From the present study we conclude that UA is a potent antioxidant molecule present in high levels among insects. Also, it appears that UA contributes to the radiation resistance of Drosophila flies. Hence, UA emerges as a promising molecule for mitigating radiation-induced oxidative damage in higher organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Maurya D, Devasagayam T, Nair C (2006) Some novel approaches for radioprotection and the beneficial effect of natural products. Indian J Exp Biol 44(2):93–114

    CAS  PubMed  Google Scholar 

  2. Levin SG, Young RW, Stohler RL (1992) Estimation of median human lethal radiation dose computed from data on occupants of reinforced concrete structures in Nagasaki, Japan. Health Phys 63(5):522–531

    Article  CAS  PubMed  Google Scholar 

  3. Paithankar JG, Deeksha K, Patil RK (2017) Gamma radiation tolerance in different life stages of the fruit fly Drosophila melanogaster. Int J Radiat Biol 93(4):440–448. https://doi.org/10.1080/09553002.2016.1266056

    Article  CAS  PubMed  Google Scholar 

  4. Paithankar JG, Raghu SV, Patil RK (2018) Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose. Int J Radiat Biol 94(6):576–589. https://doi.org/10.1080/09553002.2018.1460499

    Article  CAS  PubMed  Google Scholar 

  5. Paithankar JG, Raghu SV, Patil RK (2018) Levels and fluxes in enzymatic antioxidants following gamma irradiation are inadequate to confer radiation resistance in Drosophila melanogaster. Mol Biol Rep 45(5):1175–1186. https://doi.org/10.1007/s11033-018-4270-0

    Article  CAS  PubMed  Google Scholar 

  6. Hilliard SD, Butz A (1969) Daily fluctuations in the concentrations of total sugar and uric acid in the hemolymph of Periplaneta americana. Ann Entomol Soc Am 62(1):71–74. https://doi.org/10.1093/aesa/62.1.71

    Article  Google Scholar 

  7. Jin M, Yang F, Yang I, Yin Y, Luo JJ, Wang H, Yang XF (2012) Uric acid, hyperuricemia and vascular diseases. Front Biosci (Landmark Ed) 17:656–669

    Article  CAS  Google Scholar 

  8. Simic MG, Jovanovic SV (1989) Antioxidation mechanisms of uric acid. J Am Chem Soc 111(15):5778–5782. https://doi.org/10.1021/ja00197a042

    Article  CAS  Google Scholar 

  9. Tasaki E, Sakurai H, Nitao M, Matsuura K, Iuchi Y (2017) Uric acid, an important antioxidant contributing to survival in termites. PLoS ONE 12(6):e0179426. https://doi.org/10.1371/journal.pone.0179426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hilliker AJ, Duyf B, Evans D, Phillips JP (1992) Urate-null rosy mutants of Drosophila melanogaster are hypersensitive to oxygen stress. Proc Natl Acad Sci USA 89(10):4343–4347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hainer BL, Matheson E, Wilkes RT (2014) Diagnosis, treatment, and prevention of gout. Am Fam Physician 90(12):831–836

    PubMed  Google Scholar 

  12. Al Bratty M, Hobani Y, Dow JAT, Watson DG (2011) Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster. Metabolomics 7(4):542–548. https://doi.org/10.1007/s11306-011-0275-6

    Article  CAS  Google Scholar 

  13. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  14. Martinek RG (1965) Micromethod for the determination of uric acid in biological fluids. J Clin Pathol 18(6):777–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Prieto P, Pineda M, Aguilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal Biochem 269(2):337–341. https://doi.org/10.1006/abio.1999.4019

    Article  CAS  PubMed  Google Scholar 

  16. Li X (2012) Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. J Agric Food Chem 60(25):6418–6424. https://doi.org/10.1021/jf204970r

    Article  CAS  PubMed  Google Scholar 

  17. Ramasarma T, Rao AV, Devi MM, Omkumar RV, Bhagyashree KS, Bhat SV (2015) New insights of superoxide dismutase inhibition of pyrogallol autoxidation. Mol Cell Biochem 400(1–2):277–285. https://doi.org/10.1007/s11010-014-2284-z

    Article  CAS  PubMed  Google Scholar 

  18. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47(2):389–394. https://doi.org/10.1016/0003-2697(72)90132-7

    Article  CAS  PubMed  Google Scholar 

  19. Iyyaswamy A, Rathinasamy S (2012) Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. J Biosci 37(4):679–688. https://doi.org/10.1007/s12038-012-9236-0

    Article  CAS  PubMed  Google Scholar 

  20. Rotruck J, Pope A, Ganther H, Swanson A, Hafeman D, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(4073):588–590. https://doi.org/10.1126/science.179.4073.588

    Article  CAS  PubMed  Google Scholar 

  21. Hamada N (2017) Ionizing radiation response of primary normal human lens epithelial cells. PLoS ONE 12(7):e0181530. https://doi.org/10.1371/journal.pone.0181530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Masson-Meyers DS, Bumah VV, Enwemeka CS (2016) A comparison of four methods for determining viability in human dermal fibroblasts irradiated with blue light. J Pharmacol Toxicol Methods 79:15–22. https://doi.org/10.1016/j.vascn.2016.01.001

    Article  CAS  PubMed  Google Scholar 

  23. Reaume AG, Knecht DA, Chovnick A (1991) The rosy locus in Drosophila melanogaster: xanthine dehydrogenase and eye pigments. Genetics 129(4):1099–1109

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Massey V, Komai H, Palmer G, Elion GB (1970) On the mechanism of inactivation of xanthine oxidase by allopurinol and other pyrazolo[3,4-d]pyrimidines. J Biol Chem 245(11):2837–2844

    CAS  PubMed  Google Scholar 

  25. Ames BN, Cathcart R, Schwiers E, Hochstein P (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 78(11):6858–6862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bernard GR, Fixler DE (1963) Uric acid content of Drosophila melanogaster during and after metamorphosis. Physiol Zool 36(3):244–249. https://doi.org/10.1086/physzool.36.3.30152310

    Article  CAS  Google Scholar 

  27. Massie HR, Shumway ME, Whitney SJ (1991) Uric acid content of Drosophila decreases with aging. Exp Gerontol 26(6):609–614

    Article  CAS  PubMed  Google Scholar 

  28. Fukai T, Ushio-Fukai M (2011) Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15(6):1583–1606. https://doi.org/10.1089/ars.2011.3999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161(2):661–672

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Datkhile KD, Mukhopadhyaya R, Dongre TK, Nath BB (2009) Increased level of superoxide dismutase (SOD) activity in larvae of Chironomus ramosus (Diptera: Chironomidae) subjected to ionizing radiation. Comp Biochem Physiol C 149(4):500–506. https://doi.org/10.1016/j.cbpc.2008.11.003

    Article  CAS  Google Scholar 

  31. Niveditha S, Deepashree S, Ramesh SR, Shivanandappa T (2017) Sex differences in oxidative stress resistance in relation to longevity in Drosophila melanogaster. J Comp Physiol B 187(7):899–909. https://doi.org/10.1007/s00360-017-1061-1

    Article  CAS  PubMed  Google Scholar 

  32. Orr WC, Sohal RS (1992) The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 297(1):35–41. https://doi.org/10.1016/0003-9861(92)90637-c

    Article  CAS  PubMed  Google Scholar 

  33. Balentine DA, Dwyer JT, Erdman JW Jr, Ferruzzi MG, Gaine PC, Harnly JM, Kwik-Uribe CL (2015) Recommendations on reporting requirements for flavonoids in research. Am J Clin Nutr 101(6):1113–1125. https://doi.org/10.3945/ajcn.113.071274

    Article  CAS  PubMed  Google Scholar 

  34. Mikami T, Sorimachi M (2017) Uric acid contributes greatly to hepatic antioxidant capacity besides protein. Physiol Res 66(6):1001–1007

    Article  CAS  PubMed  Google Scholar 

  35. Chigurupati S, Mughal MR, Chan SL, Arumugam TV, Baharani A, Tang SC, Yu QS, Holloway HW, Wheeler R, Poosala S, Greig NH, Mattson MP (2010) A synthetic uric acid analog accelerates cutaneous wound healing in mice. PLoS ONE 5(4):e10044. https://doi.org/10.1371/journal.pone.0010044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors acknowledge the Board of Research in Nuclear Sciences (BRNS) and the Radiation Facility provided by the Centre for Application of Radioisotopes and Radiation Technology (CARRT), Mangalore University. Shamprasad Varija Raghu is supported by DBT-Ramalingaswami Re-entry Fellowship (Grant No: 102/IFD/SAN/1997/2015-16). Jagdish Gopal Paithankar thanks University Grants Commission (UGC), India for awarding research fellowship. Jagdish Gopal Paithankar also thank the Council of Scientific and Industrial Research (CSIR) for award of research associate and finacial assistance (Grant No: 09/1257(0001)/2019-EMR-I). The authors thank Dr. Ashwini Prabhu, Yenepoya Research Centre, Deralakatte, Karnataka, India, for carrying out cell culture studies and providing the data. All the authors thank DST-FIST Laboratory, Department of Biosciences, Mangalore University for providing the Gel Documentation Facility.

Author information

Author notes

  1. Jagdish Gopal Paithankar

    Present address: Division of Environmental Health and Toxicology, Nitte University Centre for Science Education and Research (NUCSER), Nitte (Deemed to be University), Mangalore, 575018, India

  2. Jagdish Gopal Paithankar and Avinash Kundadka Kudva contributed equally to this work.

Authors and Affiliations

  1. Department of Applied Zoology, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Jagdish Gopal Paithankar & Rajashekhar K. Patil

  2. Department of Biochemistry, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Avinash Kundadka Kudva

  3. Neurogenetics Lab, Department of Applied Zoology, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Shamprasad Varija Raghu

Authors
  1. Jagdish Gopal Paithankar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avinash Kundadka Kudva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shamprasad Varija Raghu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajashekhar K. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. JGP, AKK and SVR performed the material preparation, data collection and analysis. The manuscript was written and approved by all the authors.

Corresponding author

Correspondence to Shamprasad Varija Raghu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paithankar, J.G., Kudva, A.K., Raghu, S.V. et al. Radioprotective role of uric acid: evidence from studies in Drosophila and human dermal fibroblast cells. Mol Biol Rep 47, 2427–2436 (2020). https://doi.org/10.1007/s11033-020-05278-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05278-w

Keywords

Search

Navigation