Endoplasmic reticulum stress mediates 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT)-induced toxicity and liver lipid metabolism changes in Nile tilapia (Oreochromis niloticus)
Chen, Li Qiao
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DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main active ingredient in an emerging water environment antifoulant, the toxicity and environmental impacts of which need to be further investigated. Thus, this study examined the toxicity of DCOIT on Nile tilapia (Oreochromis niloticus), including its effects on behavior, respiration and energy metabolism as well as the role of endoplasmic reticulum stress (ER stress) in mediating its toxicity and metabolic changes. The changes in fish behavior, respiration, neuronal signal transmission, energy metabolism, ER stress, and liver histology were examined via acute (4 days) and chronic (28 days) exposures to 0, 3, 15, 30 μg/L DCOIT in vivo. Additionally, ER stress levels were measured in 24-h periods of hepatocyte exposure to 0, 3, 15, 30 and 300 μg/L DCOIT in vitro. The hyper-locomotor activities decreased, but the respiration rate increased after a 4-day acute exposure period, indicating that DCOIT exposure altered fish energy metabolism. After acute exposure at a low DCOIT concentration, the activation of ER stress induced triglyceride accumulation in the liver. After chronic exposure for 28 days, the prolonged ER stress induced a series of pathological cellular changes. At the cellular level, exposure to a high DCOIT concentration induced ER stress in the hepatocytes. In addition, as a neurotoxin, DCOIT has the potential to disrupt the neurotransmission of the cholinergic system, resulting in motor behavior disruption. This study demonstrates that DCOIT plays a role in time- and concentration-dependent toxicity and that changes in lipid metabolism are directly related to endoplasmic reticulum function after exposure to an antifouling agent. This work advances the understanding of the toxic mechanism of DCOIT, which is necessary for its evaluation.
© 2018 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (July 2018) in accordance with the publisher’s archiving policy