Ellagic Acid Mitigates Lead (Pb)-Induced Toxicity in Cyprinus carpio: A Multi-Biomarker Assessment of Hematological, Immunological, and Oxidative Stress Responses Supported by Molecular Docking

Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) using a multi-biomarker approach and molecular docking. Fish were assigned to six experimental groups: control, EA-treated, Pb-I, Pb-I + EA, Pb-II, and Pb-II + EA. Fish in the Pb-I and Pb-II groups were exposed to 2.5 and 5 mg/L Pb, respectively, while EA was administered via diet at 100 mg/kg for 14 days. At the end of the exposure period, hematological indices, innate immune parameters, and oxidative stress biomarkers were assessed in blood, liver, kidney, and gill tissues. Pb exposure caused marked hematological impairment, suppressed immune responses, increased malondialdehyde levels, and disrupted antioxidant defense by reducing SOD, CAT, GSH-Px, and GSH levels while increasing GST activity. In contrast, dietary EA supplementation significantly mitigated Pb-induced alterations, improved hematological and immunological responses, reduced lipid peroxidation, restored antioxidant capacity, and normalized GST activity to control levels. Molecular docking analyses further showed that EA interacts with hemoglobin and immunoglobulin M, supporting its potential role in preserving oxygen transport and immune functions under Pb-induced stress. Overall, the findings demonstrate that Pb-induced toxicity involves coordinated disruption of redox homeostasis and immune function, whereas EA exerts a multi-target protective effect through biochemical and molecular mechanisms. This study provides mechanistic insight into chemical–biological interactions and supports the potential application of natural bioactive compounds in mitigating heavy metal-induced toxicity.