Coenzyme Q10 Alleviates DEHP-Induced Immune Dysfunction in Juvenile Rats by Enhancing the Immunoexpression of Nrf2, PPARγ, and CD4 and Attenuating Oxidative, Inflammatory, and Apoptotic Responses
Abstract
Bis(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is known to disrupt immune homeostasis through various mechanisms. This study investigated the protective potential of coenzyme Q10 (Q10) against DEHP-induced immunotoxicity in juvenile male Sprague-Dawley rats. A total of forty 3-week-old juvenile rats were randomly assigned to four experimental groups: a control group, a Q10-treated group (10 mg/kg b.wt), a DEHP-treated group (500 mg/kg b.wt), and a combined DEHP plus Q10 group. All treatments were administered orally over 35 days. DEHP exposure significantly altered hematological parameters, with leukocytosis, neutropenia, and lymphocytosis. Serum immune markers revealed marked elevations in immunoglobulin G, immunoglobulin M, and complement 3 levels, accompanied by a significant decline in nitric oxide. Splenic oxidative stress was evident through reduced activities of catalase, reduced glutathione, and superoxide dismutase, alongside a significant rise in malondialdehyde. Inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) and the apoptotic mediator Caspase-3 were markedly upregulated, confirming inflammation-driven apoptosis. Immunohistochemical analysis demonstrated a reduction in CD4⁺ T-cell expression, along with decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPARγ) immunoexpression in splenic tissue. Co-administration of Q10 significantly mitigated these DEHP-induced alterations, restoring antioxidant enzyme activity, rebalancing immune parameters, reducing cytokine and caspase-3 expression, and increasing Nrf2, CD4⁺ T-cell, and PPARγ-immunoexpression. Overall, the data suggest that Q10 confers immune protection against DEHP exposure in a juvenile rat model, probably by reducing oxidative damage, inflammatory responses, and apoptotic reactions.