PUBLICATION
Assessment of diphenhydramine toxicity - Is its mode of action conserved between human and zebrafish?
- Authors
- Barreto, A., Santos, J., Capitão, A., Eusébio, R., Pinheiro Damasceno, É., Luísa Machado, A., Rocha, L.S., Calisto, V., Amorim, M.J.B., Maria, V.L.
- ID
- ZDB-PUB-220505-8
- Date
- 2022
- Source
- Environment International 164: 107263 (Journal)
- Registered Authors
- Amorim, Monica
- Keywords
- Freshwater fish, Mechanisms of toxicity, Multi-biomarkers, Pharmaceuticals, Risk evaluation
- MeSH Terms
-
- Animals
- Antioxidants
- Dihydrotachysterol/pharmacology
- Diphenhydramine/toxicity
- Embryo, Nonmammalian
- Humans
- Larva
- Water Pollutants, Chemical*/pharmacology
- Zebrafish*
- PubMed
- 35504231 Full text @ Environ. Int.
Citation
Barreto, A., Santos, J., Capitão, A., Eusébio, R., Pinheiro Damasceno, É., Luísa Machado, A., Rocha, L.S., Calisto, V., Amorim, M.J.B., Maria, V.L. (2022) Assessment of diphenhydramine toxicity - Is its mode of action conserved between human and zebrafish?. Environment International. 164:107263.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping