1. Assessing the impact of COVID-19 era drug combinations on hepatic functionality: A thorough investigation in adult Danio rerio.
- Author
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Onofre-Camarena DB, Elizalde-Velázquez GA, Gómez-Oliván LM, García-Medina S, Galar-Martínez M, Jerónimo Juárez JR, and Herrera-Vázquez SE
- Subjects
- Animals, Dexamethasone pharmacology, COVID-19, Apoptosis drug effects, COVID-19 Drug Treatment, Superoxide Dismutase metabolism, Lipid Peroxidation drug effects, Catalase metabolism, Water Pollutants, Chemical toxicity, Zebrafish, Liver drug effects, Liver metabolism, Oxidative Stress drug effects, Acetaminophen toxicity, Metformin pharmacology
- Abstract
Current and thorough information on the ecotoxicological consequences of pharmaceuticals is accessible globally. However, there remains a substantial gap in knowledge concerning the potentially toxic effects of COVID-19 used drugs, individually and combined, on aquatic organisms. Given the factors above, our investigation assumes pivotal importance in elucidating whether or not paracetamol, dexamethasone, metformin, and their tertiary mixtures might prompt histological impairment, oxidative stress, and apoptosis in the liver of zebrafish. The findings indicated that all treatments, except paracetamol, augmented the antioxidant activity of superoxide dismutase (SOD) and catalase (CAD), along with elevating the levels of oxidative biomarkers such as lipid peroxidation (LPX), hydroperoxides (HPC), and protein carbonyl content (PCC). Paracetamol prompted a reduction in the activities SOD and CAT and exhibited the most pronounced toxic response when compared to the other treatments. The gene expression patterns paralleled those of oxidative stress, with all treatments demonstrating overexpression of bax, bcl2, and p53. The above suggested a probable apoptotic response in the liver of the fish. Nevertheless, our histological examinations revealed that none of the treatments induced an apoptotic or inflammatory response in the hepatocytes. Instead, the observed tissue alterations encompassed leukocyte infiltration, sinusoidal dilatation, pyknosis, fatty degeneration, diffuse congestion, and vacuolization. In summary, the hepatic toxicity elicited by COVID-19 drugs in zebrafish was less pronounced than anticipated. This attenuation could be attributed to metformin's antioxidant and hormetic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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