The regulatory effects of exogenous hydrogen on mebendazole stress in mandarin fish (Siniperca chuatsi)

Mebendazole (MBZ) is often responsible for oxidative stress damage in fish during aquaculture. This study aims to investigate the protective effects of exogenous hydrogen (administered as hydrogen-rich water, HRW) on mandarin fish ( Siniperca chuatsi ) under MBZ stress. A total of 2400 fish (33 ± 2 g) were randomly assigned to a control group (no hydrogen) and three hydrogen-treated groups (H1, H2, and H3), exposed to hydrogen (200–250 ppb) for 1, 2, and 3 h per day, respectively. After 60 days, fish were subjected to 2 mg/L MBZ for 24 h. Serum and liver samples were collected at 0, 6, 12, and 24 h for biochemical and gene expression analyses, with liver histopathology examined at 24 h. Results indicated that MBZ induced hepatocyte edema, vacuolization, and central vein deformation. Hydrogen administration, especially in the H1 group, markedly alleviated tissue injury. It significantly reduced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels ( P< 0.05); enhanced activities of alkaline phosphatase (AKP), catalase (CAT), and superoxide dismutase (SOD) ( P< 0.05); up-regulated catalase ( cat ) and superoxide dismutase ( sod ) mRNA levels; and down - regulated interleukin-1β ( il-1β ), tumor necrosis factor-α ( tnf-α ), and interleukin-8 ( il-8 ) mRNA levels ( P< 0.05) . The H1 group demonstrated the most pronounced protective effect. These findings suggest that exogenous hydrogen may enhance antioxidant and anti-inflammatory capacity in mandarin fish under MBZ stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, offering a theoretical basis for alleviating aquaculture drug-induced damage.