Illicit drug ketamine induces adverse effects from behavioral alterations and oxidative stress to p53-regulated apoptosis in medaka fish under environmentally relevant exposures
Journal
Environmental Pollution
Journal Volume
237
Pages
1062-1071
Date Issued
2018
Author(s)
Abstract
With increasing problems of drug abuse worldwide, aquatic ecosystems are contaminated by human pharmaceuticals from the discharge of hospital or municipal effluent. However, ecotoxicity data and related toxic mechanism for neuroactive controlled or illicit drugs are still lacking, so assessing the associated hazardous risk is difficult. This study aims to investigate the behavioral changes, oxidative stress, gene expression and neurotoxic or apoptosis effect(s) in larvae of medaka fish (Oryzias latipes) with environmentally relevant exposures of ketamine (KET) solutions for 1–14 days. KET exposure at an environmentally relevant concentration (0.004 μM) to 40 μM conferred specific patterns in larval swimming behavior during 24 h. At 14 days, such exposure induced dose- and/or time-dependent alteration on reactive oxygen species induction, the activity of antioxidants catalase and superoxide dismutase, glutathione S-transferase and malondialdehyde contents in fish bodies. KET-induced oxidative stress disrupted the expression of acetylcholinesterase and p53-regulated apoptosis pathways and increased caspase expression in medaka larvae. The toxic responses of medaka larvae, in terms of chemical effects, were qualitatively analogous to those of zebrafish and mammals. Our results implicate a toxicological impact of waterborne KET on fish development and human health, for potential ecological risks of directly releasing neuroactive drugs-containing wastewater into the aquatic environment. Environmentally relevant concentrations of ketamine exposures induce behavioral alteration, oxidative stress and p53-regulated apoptosis in medaka fish. © 2017 Elsevier Ltd
Subjects
Apoptosis; Fish locomotion; Ketamine; Medaka (Oryzias latipes); Neurotoxicity; Oxidative stress
Other Subjects
Amines; Aquatic ecosystems; Cell death; Effluents; Enzymes; Fish; Gene expression; Health risks; Oxidative stress; Risk assessment; Toxicity; Glutathione S-transferases; Human pharmaceuticals; Ketamine; Neurotoxicity; Oryzias latipes; Potential ecological risk; Reactive oxygen species; Super oxide dismutase; Controlled drug delivery; acetylcholinesterase; catalase; glutathione transferase; illicit drug; ketamine; malonaldehyde; protein p53; reactive oxygen metabolite; superoxide dismutase; acetylcholinesterase; antioxidant; catalase; ketamine; malonaldehyde; protein p53; reactive oxygen metabolite; street drug; superoxide dismutase; apoptosis; behavioral response; drug; fish; gene expression; larva; locomotion; oxidative stress; toxicity; adverse event; animal behavior; animal experiment; animal tissue; apoptosis; aquatic environment; Article; behavior disorder; concentration (parameters); controlled study; drug exposure; ecotoxicity; embryo; environmental exposure; enzyme activity; gene expression; larva; mammal; neurotoxicity; nonhuman; Oryzias latipes; oxidative stress; protein expression; swimming; tissue level; waste water; water contamination; zebra fish; animal; apoptosis; drug effect; metabolism; Oryzias; oxidative stress; physiology; toxicity; water pollutant; Danio rerio; Mammalia; Oryzias latipes; Oryziinae; Acetylcholinesterase; Animals; Antioxidants; Apoptosis; Behavior, Animal; Catalase; Environmental Exposure; Ketamine; Larva; Malondialdehyde; Oryzias; Oxidative Stress; Reactive Oxygen Species; Street Drugs; Superoxide Dismutase; Swimming; Tumor Suppressor Protein p53; Water Pollutants, Chemical
Type
journal article