Prosopis africana Pod Methanolic Extract Attenuates Multi-Metal Oxidative Injury in Thyroid and Thymus: Evidence for...

Heavy metal mixtures (HMMs) containing lead (Pb), cadmium (Cd), and arsenic (As) induce oxidative stress and inflammation in thyroid and thymic tissues, disrupting endocrine and immune homeostasis. While Prosopis africana pod methanolic extract (PA) exhibits antioxidant properties, its protective mechanisms against multi-metal toxicity remain undefined. This study investigated PA's efficacy in mitigating HMM-induced organ injury in rats. Male Sprague-Dawley rats (n = 5/group) received environmentally relevant HMM [PbCl₂ (20 mg/kg), CdCl₂ (1.61 mg/kg), Na₂AsO₃ (10 mg/kg)] via drinking water with concurrent daily oral gavage of PA extract (500, 1000, or 1500 mg/kg) for 60 days. Tissue metal accumulation was quantified by atomic absorption spectrophotometry and oxidative stress markers spectrophotometrically. Inflammatory mediators (TNF-α), apoptotic markers (caspase-3), and pathway regulators (Nrf2, NF-κB) were measured by ELISA. Histopathological evaluation and multivariate analyses were performed. PA extract, rich in flavonoids and tannins, exhibited dose-dependent protective effects. Co-treatment significantly reduced Pb, Cd, and As accumulation in thyroid and thymus (up to 82% reduction in thyroid Cd at 1500 mg/kg compared to HMM controls, p < 0.05). Oxidative balance was restored, evidenced by a 79% decrease in malondialdehyde and recovery of antioxidant enzyme activities (SOD, CAT, GSH, GPx). PA normalized dysregulated Nrf2 expression and suppressed NF-κB activation, restoring functional antioxidant responses, resulting in marked attenuation of TNF-α (95% reduction) and caspase-3 (76% reduction). These biochemical improvements correlated with the prevention of HMM-induced organomegaly and preservation of normal histoarchitecture. Prosopis africana pod methanolic extract confers significant protection against HMM-induced thyroid and thymic injury through dual mechanisms: (i) substantial reduction of tissue metal bioaccumulation (up to 82% reduction in thyroid Cd), and (ii) restoration of functional Nrf2-mediated antioxidant responses while suppressing NF-κB-driven inflammation. Critically, PA normalized suggesting dysregulated compensatory Nrf2 elevation while enhancing antioxidant enzyme activities, demonstrating functional pathway restoration rather than mere suppression. These findings highlight PA's potential as a multi-targeted phytotherapeutic agent for mitigating heavy metal toxicity, warranting further mechanistic and translational studies.