LAUSR

Abstract The present study aimed to evaluate the protective effects of emodin on cyclophosphamide (CY)-induced oxidative injury in peripheral blood leukocytes (PBLs) of blunt snout bream and the potential mechanisms. We examined the cell viability, lactate dehydrogenase (LDH) release, apoptosis, mitochondrial membrane potential (Δѱm), reactive oxygen species (ROS) generation and correlative gene expression of nuclear factor-erythroid 2 related factor-2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signaling molecules. For the control group, PBLs were maintained in normal cell culture medium for 12 h. For the CY group, cells were exposed to 0.32 mg/mL CY for 6 h, followed by maintaining in RPMI-1640 complete medium for an additional 6 h. Cells in the CY + Emodin group were exposed to 0.32 mg/mL CY for 6 h, and then exposed to 0.20 μg/mL emodin for 6 h. We observed that emodin significantly inhibited CY-induced apoptosis in PBLs through increasing cell viability and decreasing LDH release. Emodin also inhibited Δѱm disruption and respiratory burst in CY-induced PBLs. In consistent with these results, emodin attenuated oxidative stress in CY-induced PBLs by significantly upregulating Nrf2, BTB and CNC homolog 1 (Bach1), superoxide dismutase (SOD) and catalase (CAT) genes while significantly downregulates Keap1 in Nrf2-Keap1 signaling pathway. These results collectively demonstrate that emodin can alleviate CY-induced oxidative stress in the PBLs of blunt snout bream, possibly through activating Nrf2-Keap1 signaling pathway. Our findings also suggest that emodin might be developed as a promising therapeutic agent for treating oxidative injury in blunt snout bream.