Acetaminophen (APAP) toxicity impairs growth and promotes fat tissue regeneration in drosophila melanogaster
Main Article Content
Abstract
Acetaminophen (APAP) is one of the main components of widely used analgesic and antipyretic drugs in clinical practice. However, an overdose of APAP can lead to toxicity, causing significant health effects. Evaluation of the impact of drugs on metabolism and toxicity has limitations when studying in human or animal models. This study utilizes the Drosophila melanogaster model to evaluate the toxic effects of APAP on growth and development. The results indicate that APAP toxicity is associated with age and sex in Drosophila. Furthermore, continuous exposure to APAP reduces the survival rate, pupal size, and promotes fat tissue regeneration in the experimental Drosophila model.
Article Details
Keywords
Drosophila Melanogaster, Acetaminophen, overdose
References
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4. Musselman LP, Kühnlein RP. Drosophila as a model to study obesity and metabolic disease. Suarez RK, Hoppeler HH, eds. Journal of Experimental Biology. 2018; 221(Suppl_1): jeb163881. doi:10.1242/jeb.163881.
5. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016; 7(2): 27-31. doi:10.4103/0976-0105.177703.
6. Ge Z, Wang C, Zhang J, Li X, Hu J. Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis. Front Physiol. 2019; 10: 660. doi:10.3389/fphys.2019.00660.
7. Akakpo JY, Ramachandran A, Jaeschke H. Novel strategies for the treatment of acetaminophen hepatotoxicity. Expert Opin Drug Metab Toxicol. 2020; 16(11): 1039-1050. doi:10.1080/17425255.2020.1817896.
8. Archana N, Nichole B, Deborah K. H. Fat-body remodeling in Drosophila melanogaster. Genesis. 2006; 44(8): 396-400. doi: 10.1002/dvg.20229.
9. Aguila JR. The Role of Larval Fat Cells in Starvation Resistance and Reproduction in Adult Drosophila Melanogaster. University of Nevada, Las Vegas; 2009. doi:10.34917/2505491.
10. Elmaci İ, Altinoz MA, Sari R, Bolukbasi FH. Phosphorylated Histone H3 (PHH3) as a Novel Cell Proliferation Marker and Prognosticator for Meningeal Tumors: A Short Review. Appl Immunohistochem Mol Morphol. 2018; 26(9): 627-631. doi:10.1097/PAI.0000000000000499.
11. Li S, Yu X, Feng Q. Fat Body Biology in the Last Decade. Annual Review of Entomology. 2019; 64(Volume 64, 2019): 315-333. doi:10.1146/annurev-ento-011118-112007.
12. Drosophila as a model to study obesity and metabolic disease. Journal of Experimental Biology. (2018) 221 (Suppl_1): jeb163881. doi:10.1242/jeb.163881.
13. Jaeschke H. Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. J Pharmacol Exp Ther. 1990; 255(3): 935-941.
14. Du K, Ramachandran A, Weemhoff JL, et al. Editor’s Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction. Toxicological Sciences. 2016; 154(2): 214-226. doi:10.1093/toxsci/kfw158.
15. Chen C, Krausz KW, Shah YM, Idle JR, Gonzalez FJ. Serum Metabolomics Reveals Irreversible Inhibition of Fatty Acid β-oxidation through the Suppression of PPARα Activation as a Contributing Mechanism of Acetaminophen-induced Hepatotoxicity. Chem Res Toxicol. 2009; 22(4): 699-707. doi:10.1021/tx800464q.
16. Tirmenstein MA, Nelson SD. Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides. J Biol Chem. 1990; 265(6): 3059-3065.
17. Luo G, Huang L, Zhang Z. The molecular mechanisms of acetaminophen-induced hepatotoxicity and its potential therapeutic targets. Exp Biol Med (Maywood). 2023; 248(5): 412-424. doi:10.1177/15353702221147563.