title: Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio).
abstract: Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life.
authors.affiliation: School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005, China; School of Environmental Science & Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Qiu
authors.affiliation: School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
authors.forename: Minghong
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.affiliation: School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Pan
authors.affiliation: School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China. Electronic address: mingyang@shu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005, China. Electronic address: wkjian@xmu.edu.cn.
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D002347:Carps; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D016328:NF-kappa B
keywords: Cytokines; Fish; Immunotoxicity; Nuclear factor-κB; Pharmaceuticals