Low dissolved oxygen increases uptake of a model calcium channel blocker and alters its effects on adult Pimephales promelas

Gavin N Saari; Samuel P Haddad; Rachel M Mole; Bridgett N Hill; W Baylor Steele; Lea M Lovin; C Kevin Chambliss; Bryan W Brooks

doi:10.1016/j.cbpc.2020.108719

Low dissolved oxygen increases uptake of a model calcium channel blocker and alters its effects on adult Pimephales promelas

Comp Biochem Physiol C Toxicol Pharmacol. 2020 May:231:108719. doi: 10.1016/j.cbpc.2020.108719. Epub 2020 Jan 24.

Authors

Gavin N Saari¹, Samuel P Haddad¹, Rachel M Mole¹, Bridgett N Hill¹, W Baylor Steele², Lea M Lovin¹, C Kevin Chambliss³, Bryan W Brooks⁴

Affiliations

¹ Department of Environmental Science, Baylor University, Waco, TX, USA; Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX, USA.
² Department of Environmental Science, Baylor University, Waco, TX, USA; Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX, USA; Institute of Biomedical Studies, Baylor University, Waco, TX, USA.
³ Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX, USA; Department of Chemistry, Baylor University, Waco, TX, USA.
⁴ Department of Environmental Science, Baylor University, Waco, TX, USA; Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX, USA; Institute of Biomedical Studies, Baylor University, Waco, TX, USA; School of Environment, Jinan University, Guangzhou, China. Electronic address: Bryan_Brooks@baylor.edu.

PMID: 31987992
DOI: 10.1016/j.cbpc.2020.108719

Abstract

Human population growth accompanied with urbanization is urbanizing the water cycle in many regions. Urban watersheds, particularly with limited upstream dilution of effluent discharges, represent worst case scenarios for exposure to multiple environmental stressors, including down the drain chemicals (e.g., pharmaceuticals) and other stressors (e.g., dissolved oxygen (DO)). We recently identified the calcium channel blocker diltiazem (DZM) to accumulate in fish plasma exceeding human therapeutic doses (e.g., C_min) in coastal estuaries impaired due to nonattainment of DO water quality standards. Thus, we examined whether DO influences DZM uptake by fish, and if changes in DO-dependent upatke alter fish physiological and biochemical responses. Low DO (3.0 mg DO/L) approximately doubled diltiazem uptake in adult fathead minnows relative to normoxic (8.2 mg DO/L) conditions and were associated with significant (p < 0.05) increases in fish ventilation rate at low DO levels. Decreased burst swim performance (U_burst) of adult fathead minnows were significantly (p < 0.05) altered by low versus normal DO levels. DO × DZM studies reduced U_burst by 13-31% from controls, though not significantly (p = 0.06). Physiological responses in fish exposed to DZM alone were minimal; however, in co-exposure with low DO, decreasing trends in U_burst appeared inversely related to plasma lactate levels. Such physiological responses to multiple stressors, when paired with internal tissue concentrations, identify the utility of employing biological read across approaches to identify adverse outcomes of heart medications and potentially other cardiotoxicants impacting fish cardiovascular function across DO gradients.

Keywords: Bioconcentration; Hypoxia; Pharmaceutical; Swimming performance; Urbanization.

MeSH terms

Animals
Cypriniformes / metabolism*
Diltiazem / toxicity*
Estuaries
Oxygen / chemistry*
Water / chemistry*
Water Pollutants, Chemical / toxicity*
Water Quality

Substances

Water Pollutants, Chemical
Water
Diltiazem
Oxygen