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

Abstract

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.

Transporter-interfering chemicals inhibit P-glycoprotein of yellowfin tuna (Thunnus albacares)

“…This is particularly important during early development where efflux transporters are highly expressed in embryos and juvenile fish to prevent xenobiotic uptake and toxicity (Brette et al, 2014;Fischer et al, 2013;Gordon et al, 2019;Incardona et al, 2014). Once in the body, TICs and other XT-evading free rider chemicals could exert sublethal toxic actions at much lower levels, specifically by impairing crucial fish sensory systems (Besson et al, 2020;Lari et al, 2020;Maryoung et al, 2015;Schlenker et al, 2019bSchlenker et al, , 2019aTierney et al, 2010). As structures from other xenobiotic transporters become available, the results of this study will serve as a framework to pave the way to identify additional TICs and to investigate their interactions with both ABC-type efflux transporters, including ABCB1, ABCG2, ABCC1 and ABCC2, and SLC-type uptake transporters, including Organic anion-transporting polypeptides (OATPs), Organic anion transporters (OATs), and Organic cation transporters (OCTs).…”

Pharmaceuticals in the Environment: Just One Stressor Among Others or Indicators for the Global Human Influence on Ecosystems?

“…As the application of new tools (or old tools in new applications) to understand nontarget effects of pharmaceuticals grows, we are continually learning that effects may be less predictable than what we may have initially expected with a well-characterized group of chemical classes such as pharmaceuticals. Examples of this include calcium channel blockers affecting the olfactory response (Lari et al, 2022) or cytochrome P450 inhibition from exposure to antimicrobials in fish (Pihlaja et al, 2022) through to effects on the sensitivity of invertebrates to other contaminants after multigenerational exposures to pharmaceuticals (Cardoso et al, 2022). Even more predictable effects, such as those on fish sexual maturation and reproduction from exposure to progestagins (Teigeler et al, 2022), may not account for all the potential impacts in organisms.…”