Phagocytic Receptors Mediate Survival and Locomotor Resilience of Ethanol-Exposed Drosophila

Authors

  • Julia Citra Prastika Faculty of Pharmacy, Hasanuddin University
  • Sri Wahyuni M Faculty of Pharmacy, Hasanuddin University
  • Reski Amalia Rosa Faculty of Pharmacy, Hasanuddin University
  • Nadila Pratiwi Latada Faculty of Pharmacy, Hasanuddin University
  • Mukarram Mudjahid Faculty of Pharmacy, Hasanuddin University
  • Risfah Yulianty Faculty of Pharmacy, Hasanuddin University
  • Firzan Nainu Faculty of Pharmacy, Hasanuddin University

DOI:

https://doi.org/10.22225/ijbstm.2.2.2025.46-51

Keywords:

Drosophila, ethanol, toxicity, innate immunity, phagocytosis

Abstract

Background Ethanol is a widely studied toxicant known to induce oxidative stress and cellular damage across species. While phagocytic clearance is essential for maintaining tissue homeostasis, its role in protecting against ethanol-induced toxicity remains poorly understood. This study aims to elucidate the role of phagocytic receptors in modulating the organism’s response to ethanol-induced toxicity using Drosophila melanogaster.

Methods To assess the functional significance of phagocytic receptors, we utilized behavioral locomotor assay and survival analysis on both wild-type and mutants deficient in the phagocytic receptors Draper and Integrin-[beta]v of Drosophila which are homologous to mammalian MEGF10 and integrins, respectively. Flies were exposed to the various concentration of ethanol, and their climbing ability and survival responses were compared across genotypes.

Results Our results revealed that mutants lacking Draper and/or Integrin-[beta]v showed a significant reduction in locomotor activity (p < 0.05 to p < 0.0001) and an approximately two-fold decrease in survival time under ethanol exposure compared with wild-type flies. These findings indicate that impaired phagocytic clearance may exacerbate ethanol toxicity.

Conclusion In summary, this study demonstrates that phagocytic receptors play a critical protective role against ethanol toxicity in D. melanogaster. The data suggest the interconnected roles of oxidative stress, apoptosis, and phagocytosis in maintaining tissue homeostasis, validating Drosophila as a robust model for investigating the effect of toxicant on the phenotypic features of metazoan species.

References

Abolaji, A., Kamdem, J. P., Farombi, O., & Rocha, J. B. (2013). Drosophila melanogaster as a Promising Model Organism in Toxicological Studies: A Mini Review. . Archives of Basic and Applied Medicine. , 1, 33-38.

Arandjelovic, S., & Ravichandran, K. S. (2015). Phagocytosis of apoptotic cells in homeostasis. Nature Immunology, 16(9), 907-917. https://doi.org/10.1038/ni.3253

As’ad, M. F., Asbah, A., Rumata, N. R., Rante, H., & Nainu, F. (2023). Pharmacological Role of Deoxycholic Acid in the Regulation of Aging in Drosophila melanogaster. Biointerface Research in Applied Chemistry, 13(6). https://doi.org/10.33263/briac136.513

Bangs, P., Franc, N., & White, K. (2000). Molecular mechanisms of cell death and phagocytosis in Drosophila. Cell Death & Differentiation, 7, 1027–1034. https://doi.org/https://doi.org/10.1038/sj.cdd.4400754

Betsuyaku, T., Ito, Y., Peake, N., Al-Bari, A. A., El-Akabawy, G., & Eid, N. (2024). Enhanced autophagy and phagocytosis of apoptotic lymphocytes in splenic macrophages of acute ethanol-treated rats: Light and electron microscopic studies. Histol Histopathol, 39(7), 853-866. https://doi.org/10.14670/HH-18-729

Buchon, N., Silverman, N., & Cherry, S. (2014). Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology. Nat Rev Immunol, 14(12), 796-810. https://doi.org/10.1038/nri3763

De Nobrega, A. K., Noakes, E. J., Storch, N. A., Mellers, A. P., & Lyons, L. C. (2022). Sleep Modulates Alcohol Toxicity in Drosophila. Int J Mol Sci, 23(20). https://doi.org/10.3390/ijms232012091

Doke, S. K., & Dhawale, S. C. (2015). Alternatives to animal testing: A review. Saudi Pharm J, 23(3), 223-229. https://doi.org/10.1016/j.jsps.2013.11.002

Khaerani, M., Chaeratunnisa, R., Salsabila, A., Asbah, A., Asri, R. M., Shiratsuchi, A., & Nainu, F. (2024). Curcumin-mediated alleviation of dextran-induced leaky gut in Drosophila melanogaster. Narra J, 4(1), e743. https://doi.org/10.52225/narra.v4i1.743

Melcarne, C., Lemaitre, B., & Kurant, E. (2019). Phagocytosis in Drosophila: From molecules and cellular machinery to physiology. Insect Biochem Mol Biol, 109, 1-12. https://doi.org/10.1016/j.ibmb.2019.04.002

Nagaosa, K., Okada, R., Nonaka, S., Takeuchi, K., Fujita, Y., Miyasaka, T., Manaka, J., Ando, I., & Nakanishi, Y. (2011). Integrin betanu-mediated phagocytosis of apoptotic cells in Drosophila embryos. J Biol Chem, 286(29), 25770-25777. https://doi.org/10.1074/jbc.M110.204503

Nainu, F., Bahar, M. A., Sartini, S., Rosa, R. A., Rahmah, N., Kamri, R. A., Rumata, N. R., Yulianty, R., & Wahyudin, E. (2022). Proof-of-Concept Preclinical Use of Drosophila melanogaster in the Initial Screening of Immunomodulators. Scientia Pharmaceutica, 90(1). https://doi.org/10.3390/scipharm90010011

Nainu, F., Shiratsuchi, A., & Nakanishi, Y. (2017). Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism. Front Immunol, 8, 1220. https://doi.org/10.3389/fimmu.2017.01220

Nguyen, T. T., Wei, S., Nguyen, T. H., Jo, Y., Zhang, Y., Park, W., Gariani, K., Oh, C. M., Kim, H. H., Ha, K. T., Park, K. S., Park, R., Lee, I. K., Shong, M., Houtkooper, R. H., & Ryu, D. (2023). Mitochondria-associated programmed cell death as a therapeutic target for age-related disease. Exp Mol Med, 55(8), 1595-1619. https://doi.org/10.1038/s12276-023-01046-5

Padovan, J. C., Dourado, T. M. H., Pimenta, G. F., Bruder-Nascimento, T., & Tirapelli, C. R. (2023). Reactive Oxygen Species Are Central Mediators of Vascular Dysfunction and Hypertension Induced by Ethanol Consumption. Antioxidants (Basel), 12(10). https://doi.org/10.3390/antiox12101813

Pandey, U. B., & Nichols, C. D. (2011). Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev, 63(2), 411-436. https://doi.org/10.1124/pr.110.003293

Parasuraman, S. (2011). Toxicological screening. J Pharmacol Pharmacother, 2(2), 74-79. https://doi.org/10.4103/0976-500X.81895

Peterson, S. K., & Ahmad, S. T. (2024). A Brief Overview of Ethanol Tolerance and Its Potential Association with Circadian Rhythm in Drosophila. Int J Mol Sci, 25(23). https://doi.org/10.3390/ijms252312605

Pratama, A. S., Rizal, A. R., Ramly, N., Bijaksana, G. F., Permatasari, J. A., Bahar, M. A., Latada, N. P., Mudjahid, M., Yulianty, R., Yanti, N. I., & Nainu, F. (2025). Phenotypical analysis of Chloramphenicol toxicity in Drosophila. International Journal of Biomedical Science and Travel Medicine (IJBSTM), 2. https://doi.org/10.22225/ijbstm.2.1.2025.19-26

Pratama, M. R., Wahyudin, E., Putri, T. Z., Hardiyanti, W., Fatiah, D., Chaeratunnisa, R., Bapulo, N. N., Latada, N. P., Mudjahid, M., & Nainu, F. (2024). A fruit fly-based approach to unraveling enteropathy-causing pharmaceuticals. Narra J, 4(2), e898. https://doi.org/10.52225/narra.v4i2.898

Pulikkot, S., Hu, L., Chen, Y., Sun, H., & Fan, Z. (2022). Integrin Regulators in Neutrophils. Cells, 11(13). https://doi.org/10.3390/cells11132025

Redza-Dutordoir, M., & Averill-Bates, D. A. (2016). Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta, 1863(12), 2977-2992. https://doi.org/10.1016/j.bbamcr.2016.09.012

Sandhu, S., Kollah, A. P., Lewellyn, L., Chan, R. F., & Grotewiel, M. (2015). An inexpensive, scalable behavioral assay for measuring ethanol sedation sensitivity and rapid tolerance in Drosophila. J Vis Exp(98). https://doi.org/10.3791/52676

Sheng, Y. R., Hu, W. T., Chen, S., & Zhu, X. Y. (2024). Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms. Front Immunol, 15, 1275203. https://doi.org/10.3389/fimmu.2024.1275203

Shiratsuchi, A., Mori, T., Sakurai, K., Nagaosa, K., Sekimizu, K., Lee, B. L., & Nakanishi, Y. (2012). Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila. J Biol Chem, 287(26), 21663-21672. https://doi.org/10.1074/jbc.M111.333807

Strzyz, P. (2017). Cell death: Pulling the apoptotic trigger for necrosis. Nat Rev Mol Cell Biol, 18(2), 72. https://doi.org/10.1038/nrm.2017.1

Tamar, L. M. A. F., Syahrir, N. I., Khansa, K., Rosa, R. A., Latada, N. P., Wahyuni, S., Rumata, N. R., Yulianty, R., Mudjahid, M., & Nainu, F. (2024). Impact of Ethanol Exposure on Survival and the Expression of Endogenous Antioxidants in Drosophila melanogaster. nternational Journal of Biomedical Science and Travel Medicine (IJBSTM), 1.

Troutwine, B. R., Ghezzi, A., Pietrzykowski, A. Z., & Atkinson, N. S. (2016). Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway. Genes Brain Behav, 15(4), 382-394. https://doi.org/10.1111/gbb.12288

Tung, T. T., Nagaosa, K., Fujita, Y., Kita, A., Mori, H., Okada, R., Nonaka, S., & Nakanishi, Y. (2013). Phosphatidylserine recognition and induction of apoptotic cell clearance by Drosophila engulfment receptor Draper. J Biochem, 153(5), 483-491. https://doi.org/10.1093/jb/mvt014

Vakifahmetoglu-Norberg, H., Ouchida, A. T., & Norberg, E. (2017). The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun, 482(3), 426-431. https://doi.org/10.1016/j.bbrc.2016.11.088

Zheng, Q., Ma, A., Yuan, L., Gao, N., Feng, Q., Franc, N. C., & Xiao, H. (2017). Apoptotic Cell Clearance in Drosophila melanogaster. Front Immunol, 8, 1881. https://doi.org/10.3389/fimmu.2017.01881

Downloads

Published

2025-09-25

Issue

Section

Articles