Little is known about the effects of the cardiovascular drug verapamil (VRP) on metabolic processes in fish. Most calcium channel blockers including VRP are metabolized by cytochrome P450 (CYP450) enzymes. In this study we investigated the in vivo effect of VRP on some CYP450-mediated reactions in juvenile rainbow trout (Oncorhynchus mykiss). Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg l(-1)) for 0, 21, and 42 day. The following CYP450-mediated reactions were studied in hepatic microsomes: O-dealkylation of ethoxyresorufin, methoxyresorufin, and pentoxyresorufin, hydroxylation of coumarin, tolbutamide, and p-nitrophenol, and O-debenzylation of 7-benzyloxy-4-trifluoromethylcoumarin. The amounts of products of these reactions did not differ among fish exposed to different levels of VRP and control fish. This suggests that the levels of VPR used did not alter catalytic activity of the selected CYP450 enzymes. In conclusion, none of the investigated CYP450-mediated reactions has potential as a biomarker to monitor VRP contamination of the aquatic environment.
- MeSH
- Biomarkers metabolism MeSH
- Calcium Channel Blockers toxicity MeSH
- Water Pollutants, Chemical toxicity MeSH
- Microsomes, Liver drug effects enzymology metabolism MeSH
- Liver drug effects enzymology metabolism MeSH
- Coumarins metabolism MeSH
- Nitrophenols metabolism MeSH
- Oncorhynchus mykiss MeSH
- Oxazines metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Verapamil toxicity MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In this study, the toxic effects of verapamil (VRP) were studied on juvenile rainbow trout, Oncorhynchus mykiss, by chronic semi-static bioassay. Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg/L) for 0, 21 and 42 d. Multiple biomarkers were measured, including morphological indices, hematological parameters and antioxidant responses of different tissues (brain, gill, liver, muscle and intestine). Based on the results, there was no significant change in all parameters measured in fish exposed to VRP at environmental related concentration, but VRP-induced stress in fish exposed to higher concentrations reflected the significant changes of physiological and biochemical responses. Through principal component analysis and integrated biomarker response assessment, effects induced by VRP-stress in each test group were distinguished. Additionally, all parameters measured in this study displayed various dependent patterns to VRP concentrations and exposure time using two-way ANOVA statistic analysis. In short, the multiple responses in fish indicated that VRP induced physiological stress and could be used as potential biomarkers for monitoring residual VRP in aquatic environment; but molecular and genetic mechanisms of these physiological responses in fish are not clear and need to be further studied.
- MeSH
- Calcium Channel Blockers toxicity MeSH
- Oncorhynchus mykiss growth & development metabolism MeSH
- Verapamil toxicity MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Verapamil (VRP) is a calcium channel blocker that is a highly prescribed compound and commonly present in aquatic environment, but the ecotoxicological effects of this pharmaceutical in fish have not been fully documented. In this study, the toxic effects of VRP were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute static bioassay. In the acute test, the median lethal concentration (LC50, 2.72 mg/L) was evaluated and the behavioral changes were obviously intensified with increasing VRP concentrations. Compared to the control, oxidative stress was observed in fish tissues with different levels after short-term exposure to sublethal concentrations (0.27 and 1.35 mg/L) of VRP. Activities of SOD and GPx in fish brain were induced at 0.27 mg/L VRP, but all the antioxidant enzymes (SOD, GPx and GR) in fish brain were decreased at 1.35 mg/L VRP. When compared to the control, all the antioxidant enzymes in gill were decreased in both treated groups, but there was no significant change in muscle. Additional, muscle DNA/RNA ratio in fish exposed at 1.35 mg/L VRP was significantly lower than that in the control. Furthermore, through chemometrics of all parameters measured in fish exposed to sublethal VRP concentrations using principal component analysis, two groups with 89.8% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in of fish indicated that VRP-induced environmental stress; but according to VRP residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future.
- MeSH
- Calcium Channel Blockers toxicity MeSH
- Water Pollutants, Chemical toxicity MeSH
- Behavior, Animal drug effects MeSH
- Brain drug effects enzymology metabolism MeSH
- Oncorhynchus mykiss physiology MeSH
- Oxidative Stress MeSH
- Reactive Oxygen Species metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Toxicity Tests, Acute MeSH
- Verapamil toxicity MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Research Support as Topic MeSH
- Medigoxin pharmacokinetics adverse effects MeSH
- Rats, Wistar physiology MeSH
- Promethazine pharmacokinetics adverse effects MeSH
- Propranolol pharmacokinetics adverse effects toxicity MeSH
- Sodium-Potassium-Exchanging ATPase adverse effects drug effects MeSH
- Synaptosomes drug effects MeSH
- Verapamil pharmacokinetics adverse effects toxicity MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Comparative Study MeSH
