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

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

doi:10.1016/j.cbpc.2020.108719

Cited by 5 publications

(10 citation statements)

References 74 publications

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“…In the present study, P BW values, which ranged from 6 to 61, were comparable to those of fathead minnows (range 1-11.8) and killifish (range 23.5-57.8). In addition, diltiazem V d estimates for rainbow trout in the present study (0.85-3 L/kg) were quite similar to those for fathead minnows (1-3.7 L/kg) by Saari et al (2020). However, V d values in both of these common freshwater fish models were markedly higher than those of the euryhaline Gulf killifish (0.19-0.28 L/kg).…”

Section: Discussionsupporting

confidence: 78%

“…In 96-h laboratory studies with an estuarine model, the Gulf killifish (Fundulus grandis), Scott et al (2019) reported BCF values ranging from 6 to 13 L/kg across various pH and salinity conditions. Also, in 96-h laboratory experiments with the fathead minnow (Pimephales promelas), Saari et al (2020) identified BCFs from 2 to 16.7 L/kg when water pH (8.1-8.4) was similar to the pH of the present study (8-8.4). More recently, Sims et al (2020) performed caged studies with rainbow trout in an effluent-dominated river, observed rapid uptake of diltiazem resulting in steady-state conditions within 24 to 72 h, and reported BCF values ranging from 10.1 to 72.6 L/kg.…”

Section: Discussionsupporting

confidence: 74%

“…However, V d values in both of these common freshwater fish models were markedly higher than those of the euryhaline Gulf killifish (0.19-0.28 L/kg). As noted by Saari et al (2020), such differences may be explained by differential plasma protein binding. Clearly, future research is needed to define mechanisms associated with such pharmacokinetic differences among freshwater and marine fish for diltiazem and other contaminants of emerging concern.…”

Section: Discussionmentioning

confidence: 97%

“…Such observations are important because fish plasma modeling, in which human plasma doses of therapeutic responses and side effects are compared to exceedance predictions in fish, appears useful for prioritizing pharmaceuticals for aquatic risks to fish (Huggett et al 2003;Fick et al 2010;Brooks 2014). Several recent studies have subsequently studied uptake and responses of several fish species to diltiazem (Saari et al 2018(Saari et al , 2020Scott et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Interaction of the Olfactory System of Rainbow Trout (Oncorhynchus mykiss) with Diltiazem

Lari

Burket

Steinkey

et al. 2020

Enviro Toxic and Chemistry

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Diltiazem is ubiquitously prescribed and has been reported in many effluents and freshwater bodies. Being a calcium channel blocker, diltiazem could disrupt the function of the sensory and central nervous systems. In the present study, using electro-olfactography (EOG), we investigated the interaction of diltiazem with the olfactory sensory neurons (OSNs) of rainbow trout by looking into the detection threshold and effects of immediate (~5 min) and acute (24 h) exposure to diltiazem at 6.6, 66, and 660 µg/L. We also studied the accumulation of the drug in fish plasma and whole body. Brief exposure to diltiazem impaired the OSN response to a chemosensory stimulus in a concentration-dependent manner at 6.6 µg/L and higher, whereas OSNs exposed for 24 h only displayed an impairment at 660 µg/L. Chemical analysis showed that the accumulation of diltiazem in fish plasma and body correlated with the EOG response because it was 10 times higher in the group that displayed a significant impairment (660 µg/L) compared to the other 2 groups (6.6, 66 µg/L). This correlation suggests that the impact of diltiazem on OSNs might partially be through the accumulated molecules in the fish bloodstream. Fish did not detect diltiazem as a sensory stimulus even at concentrations as high as 660 µg/L; thus, fish could potentially swim toward or fail to escape harmful concentrations of diltiazem.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction of the Olfactory System of Rainbow Trout (Oncorhynchus mykiss) with Diltiazem

Lari

Burket

Steinkey

et al. 2020

Enviro Toxic and Chemistry

Self Cite

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“…The latter can include an interlamellar cell mass (present in some species in normoxia) which atrophies in hypoxic conditions revealing a much greater lamellar area (Nilsson, Dymowska & Stecyk, 2012; Wood & Eom, 2021). These factors that enhance functional gill area and gas exchange during hypoxia may simultaneously also enhance xenobiotic uptake rates (Sundin & Nilson, 1998; Val, 2000; Du et al ., 2018; Gilmour & Perry, 2018; Saari et al ., 2020).…”

Section: Water Physico‐chemistry and The Risk Of Chemicalsmentioning

confidence: 99%

Global variation in freshwater physico‐chemistry and its influence on chemical toxicity in aquatic wildlife

et al. 2021

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Chemical pollution is one of the major threats to global freshwater biodiversity and will be exacerbated through changes in temperature and rainfall patterns, acid–base chemistry, and reduced freshwater availability due to climate change. In this review we show how physico‐chemical features of natural fresh waters, including pH, temperature, oxygen, carbon dioxide, divalent cations, anions, carbonate alkalinity, salinity and dissolved organic matter, can affect the environmental risk to aquatic wildlife of pollutant chemicals. We evidence how these features of freshwater physico‐chemistry directly and/or indirectly affect the solubility, speciation, bioavailability and uptake of chemicals [including via alterations in the trans‐epithelial electric potential (TEP) across the gills or skin] as well as the internal physiology/biochemistry of the organisms, and hence ultimately toxicity. We also show how toxicity can vary with species and ontogeny. We use a new database of global freshwater chemistry (GLORICH) to demonstrate the huge variability (often >1000‐fold) for these physico‐chemical variables in natural fresh waters, and hence their importance to ecotoxicology. We emphasise that a better understanding of chemical toxicity and more accurate environmental risk assessment requires greater consideration of the natural water physico‐chemistry in which the organisms we seek to protect live.

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Factors Affecting the Binding of Diltiazem to Rainbow Trout Plasma: Implications for the Risk Assessment of Pharmaceuticals in Aquatic Systems

Glover

Klaczek

Goss

et al. 2022

Enviro Toxic and Chemistry

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The accumulation of organic toxicants in fish plasma, and how they partition between the bound and unbound fraction once absorbed, are important metrics in models that seek to predict the risk of such contaminants in aquatic settings. Rapid equilibrium dialysis of diltiazem, an ionizable weak base and important human pharmaceutical contaminant of freshwaters, was conducted with rainbow trout (Oncorhynchus mykiss) plasma. The effect of fed state, fish sex, fish strain/size, and dialysis buffer pH on the binding of radiolabeled diltiazem (9 ng ml −1 ) was assessed. In fed fish, 24.6%-29.5% of diltiazem was free, unbound to plasma proteins. Although starvation of fish resulted in a decrease in plasma protein, the bound fraction of diltiazem remained relatively constant. Consequently, the protein-bound concentration of diltiazem increased with length of starvation. In general, rainbow trout strain was a significant factor affecting plasma binding, although the two strains tested also differed markedly in size. Dialysis buffer pH significantly influenced plasma binding, with a higher unbound diltiazem fraction at pH 6.8 than pH 8.0. These data indicate that empirical measures of plasma binding in fish are important for accurate risk assessment and that the physiological status of a fish is likely to impact its sensitivity to toxicants such as diltiazem.

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

Cited by 5 publications

References 74 publications

Interaction of the Olfactory System of Rainbow Trout (Oncorhynchus mykiss) with Diltiazem

Interaction of the Olfactory System of Rainbow Trout (Oncorhynchus mykiss) with Diltiazem

Global variation in freshwater physico‐chemistry and its influence on chemical toxicity in aquatic wildlife

Factors Affecting the Binding of Diltiazem to Rainbow Trout Plasma: Implications for the Risk Assessment of Pharmaceuticals in Aquatic Systems

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