Methylmercury, cadmium and arsenic(III)-induced toxicity, oxidative stress and apoptosis in Pacific red snapper leukocytes

•MeHg, Cd and As(III) are three priority hazardous pollutant metals worldwide.•Cell viability is compromised by metal exposition in fish leukocytes.•MeHg, Cd and As(III) up-regulated apoptosis-related genes in leukocytes.•ROS production and antioxidant activity in leukocytes is affected by MeHg, Cd and As(III).•Selected immune parameters and genes are modulated in leukocytes exposed to metals. Methylmercury (MeHg), cadmium (Cd) and arsenic (As(III)) are among the most toxic metals in aquatic systems that have been associated with multiple animal and human health problems. This study investigated cytotoxic, oxidative stress, and apoptosis effects on fish leukocytes following their exposure to metals. A preliminary study indicated that leukocytes exposed to MeHg at a concentration of 0.01 mM, Cd at 0.05 mM, and As(III) at 2 mM showed a time-dependent cell viability reduction (around 40%), so they were selected for further experiments. To evaluate the effect of MeHg, Cd and As(III) on Pacific red snapper Lutjanus peru, we measured cytotoxicity, reactive oxygen species, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)), nitric oxide production, apoptosis-related and immune-related genes on head-kidney and spleen leukocytes following exposure to MeHg (0.01 mM), Cd (0.05 mM) and As(III) (2 mM) for 30 min and 2 h. Reactive oxygen species (ROS) generation highly increased in time-dependent doses in head-kidney leukocytes compared with the control group. Regarding antioxidant activity, SOD increased significantly in leukocytes exposed to any heavy metals after two h. Expressly, CAT activity decreased in those leukocytes exposed to Cd and As(III). Apoptotic function genes (Casp-2, Casp-3, and Casp-7) strongly up-regulated after heavy metal exposure, but Cd was more toxic. Finally, granzyme A and perforin 1 strongly up-regulated in leukocytes exposed to MeHg and As(III) compared with the control group. Our data showed that MeHg, Cd, and As(III) might have been cytotoxic and induced oxidative stress and apoptosis with possible biological consequences in fish.