In Vitro Cyclooxygenase Inhibition Assay for Evaluating Ecotoxicity of the Surface Water and Domestic Wastewater in the Tone Canal, Japan

Abstract

Cyclooxygenase (COX) plays an important role in eicosanoid metabolism. Nonsteroidal anti-inflammatory drugs (NSAIDs) function as COX inhibitors and are frequently detected in the aquatic environment. Here, we measured the in vitro COX-inhibiting activity of the surface water and domestic wastewater in the Tone Canal, Japan. The concentrations of several NSAIDs in the some samples were also determined using gas chromatography-tandem mass spectrometry for confirming the validity of the assay. The target compounds were extracted from the samples using a solid-phase extraction cartridge. A dose-response relationship between the inhibiting activity and sample volume were observed in the wastewater sample. The higher COX-inhibiting activities were observed in the wastewater sample, as compared with the samples of the surface water in the canal. These inhibiting activities reflected the trends of NSAIDs distribution in the canal. However, the inhibiting activities of the water samples could not be entirely explained by the NSAIDs that were selected for instrumental analysis in this study. Other compounds that were not measured by instrumental analysis in this study might contribute to the inhibiting activities. Therefore, the COX-inhibiting assay would be effective for evaluating inclusive ecotoxicity in the aquatic environment.

Monitoring the concentrations of nonsteroidal anti-inflammatory drugs and cyclooxygenase-inhibiting activities in the surface waters of the Tone Canal and Edo River Basin

“…According to the results of our previous study, the COX-2-inhibiting activities of environmental water samples are weaker than the COX-1-inhibiting activities of the same samples. [13] Furthermore, COX-1 plays an important role in gastrulation and vascular tube formation during development in zebrafish, as reported in a previous study. [20] COX-1 activity can also be assessed with more sensitivity and may be the main cause of the adverse effects of NSAIDs; therefore, we mainly assessed COX-1 activity in this study.…”

“…However, in our previous study, it became apparent that the COX-1-inhibiting activities could not be explained by the investigated NSAIDs. [13] Given this phenomenon, other NSAIDs that were not investigated in this study and/or other chemicals that have the potential to act as COX inhibitors (e.g., NSAID metabolites) may contribute to some of the observed COX-1-inhibiting activity (particularly that observed between August and December). Therefore, there is a concern that COX inhibitors in surface waters could influence aquatic organisms to a greater extent than we expected based on the measured NSAID concentrations, and further studies examining COX inhibitors in aquatic environments are necessary.…”

“…In our previous study, we reported the validity of using an in vitro COX inhibition assay to evaluate inclusive aquatic ecotoxicity. [13] Although an assay focused on mode of action would be effective for evaluating the ecotoxicological effects of NSAIDs and other COX inhibitors in the aquatic environment, data describing the COX-inhibiting activities in such environments are still insufficient, particularly seasonal variations in such COXinhibiting activities.…”

Fixed Bed Modeling of Nonsteroidal Anti-Inflammatory Drug Removal by Ion-Exchange in Synthetic Urine: Mass Removal or Toxicity Reduction?

“…It was determined that a no single battery of assays should be applied universally but rather tailored to fit the specific needs of the application. 19 For example, Nishi et al 22 evaluated NSAID ecotoxicity in surface water and wastewater using an in vitro cyclooxygenase (COX) inhibition bioassay, which is the primary mode of action of NSAIDs, and a dose−response relationship was observed between COX inhibition and NSAID concentration. However, this study did not evaluate the specific activity of pharmaceutical metabolites.…”

Emerging Pollutants

“…studied the exposure of marine mussels to propranolol and acetaminophen and they examined the responses of Mytilus galloprovincialis as a sentinel species to test the effects on a behavior parameter, xenobiotic metabolism and oxidative stress. Some enzymatic activities in liver were reduced after propranolol exposure whereas acetaminophen enhanced them Nishi, et al (2010). measured the in vitro cyclooxygenase (COX)-inhibiting activity of the surface water and domestic wastewater in the Tone Canal, Japan.…”