Assessment of diphenhydramine toxicity – Is its mode of action conserved between human and zebrafish?. (June 2022)

• Record Type: Journal Article
• Authors: Barreto, Angela; Santos, Joana; Capitão, Ana; Eusébio, Rodrigo; Pinheiro Damasceno, Évila; Luísa Machado, Ana; Rocha, Luciana S.; Calisto, Vânia; Amorim, Mónica J.B.; Maria, Vera L.
• Is Part Of: Environment international. Volume 164(2022)
• Publication Date: 2022-06
• Subjects: Pharmaceuticals -- Freshwater fish -- Multi-biomarkers -- Risk evaluation -- Mechanisms of toxicity; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107263
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Diphenhydramine (DPH, 10 mg/L) reduced zebrafish embryos heartbeat rate (48 h); DPH, 1 and 10 mg/L, induced larvae hypoactivity and erratic swimming, after 120 h; DPH, 0.01 or 10 mg/L, reduced energy budgets and total glutathione content (96 h); DPH affected cholinesterase/glutathione S-transferase activities and DNA integrity; DPH target molecules are conserved in human and zebrafish. Abstract: The main aim of the study is to evaluate the effects of the pharmaceutical diphenhydramine (DPH) on embryo-larvae Danio rerio across distinct levels of organization – individual and subcellular – and correlate those effects with the DPH mode of action (MoA) assessed by in silico analysis. An embryos heartbeat rate reduction was observed at 10 mg/L DPH, but 0.001 to 10 mg/L did not significantly affect the zebrafish survival, hatching and morphology. Larvae swimming distance decreased (hypoactivity) at 1 and 10 mg/L DPH. Moreover, the straightforward movements decrease and the increase in the zigzag movements or movements with direction changes, shown an erratic swimming behavior. Energy budgets decreased for lipid (0.01 mg/L DPH) and carbohydrate (10 mg/L DPH) contents. Cholinesterase (neural function) and glutathione S-transferase (Phase II biotransformation/antioxidant processes) increased their activities at 10 mg/L DPH, where a decrease in the total glutathione content (antioxidant system) was observed. DNA damage was found at 0.01 and 10 mg/L DPH. However, a DNA repair occurred after subsequent 72 h in clean media. The in silico study revealed a relevant conservation between human and zebrafish DPH target molecules. These data provide a valuable ecotoxicological information about the DPH effects and MoA to non-target organisms.