Nodularin (NOD) is a hazardous material widely detected in water blooms. Fish immune cells are extremely vulnerable to NOD-induced oxidative stress. Oligomeric proanthocyanidin complex (OPC), extracted from grapeseed, was used as an antioxidant to eliminate reactive oxygen species and prevent apoptotic effects. Carassius auratus lymphocytes were treated with different concentrations (0, 10, 100, and 1000 mu g/L) of OPC and a constant dose (100 mu g/L) of NOD for 12h in vitro. OPC inhibited mitosis by decreasing intracellular levels of oxidative stress, regulating antioxidant enzymes (CAT, SOD, GPx, GR, and GST), mediating bcl-2 family proteins, and deactivating caspase-3. Glutathione (GSH) levels in group V (NOD 100 mu g/L; OPC 1000 mu g/L) showed a twofold increase compared with corresponding levels in group II (NOD 100 mu g/L). Structure parameters of NOD and NOD-GSH were calculated using SYBYL 7.1 software. ClogP and HINK logP values of NOD-GSH decreased by 10.4- and 2.3-fold, respectively, compared with corresponding values of NOD. OPC-stimulated GSH can lower the lipophilicity and polarity of NOD. OPC, as a protective agent, can alleviate NOD-induced toxicity in C. auratus lymphocytes by regulating oxidative stress and inducing NOD-GSH detoxification. (C) 2014 Elsevier B.V. All rights reserved.