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Although the number of studies documenting the presence of Microplastics (MP) in fish is increasing, research studies focused on its detoxification are very limited. In this study, rainbow trout (Oncorhyncus mykiss) were randomly divided into two groups after being fed with MPs (15% polypropylene [PP] +15% polyethylene [PE]) for 2 months. MP excretion without any application (PP+PE) in group I fish, and excretion of MPs with hydrogen-rich water (HRW) application (PP+PE+HRW) in group 2 were investigated under semi-static conditions for 21 days. This effect was also compared by using positive and negative control groups (Control [no treatment, free PP, PE or/and HRW] and only HRW group). In this direction, the following were determined: PP+PE chronic toxicity in aquatic organisms, the toxicity mechanism and the effect of HRW as a possible treatment method in blood tissue; with hematological indices ([RBC count [RBC], leukocyte count [WBC], hemoglobin value [Hb], hematocrit ratio [Hct], platelet count [PLT], hemoglobin count per erythrocyte [MCHC], mean hemoglobin amount per erythrocyte [MCH] and mean erythrocyte volume [MCV]) in other tissues (liver, gill and brain tissue) oxidative stress response (catalase [CAT]), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen products (ROS), malondialdehyde ([MDA] levels), DNA damage (8-OHdG: 8-Hydroxy-2-Deoxyguanosine), and the apoptosis (caspase 3) levels were investigated. In addition, acetylcholinesterase enzyme (AChE) activity, which is important in neurotoxicity pathways in the brain, was determined. The presence of plastics (PP/PE) in target tissues (muscle, liver, gill and gastrointestinal tract) was also obtained. The results showed that PP+PE caused toxicity in all three tissues. MPs showed an inhibiting effect on antioxidant enzyme activities and an inductive effect on MDA, ROS, 8-OHdG, and caspase 3 levels. HRW showed a mitigating effect on MP-mediated toxicity in O. mykiss brain, blood, gill, and liver by controlling the ROS/GSH/MDA pathway. HRW can be suggested as a costeffective and eco-friendly curative for the protection of fish from the oxidative damages produced by the ingestion of microplastics. [ABSTRACT FROM AUTHOR]