RESUMEN
Titanium dioxide nanoparticle (TNP) has been suggested for use in fish farms to prevent or alleviate bacterial diseases owing to its bactericidal property. Unfortunately, the interaction of TNP with cells impaired the host defenses of fish resulting in increased mortality during bacterial challenges. The present study evaluated the efficacy of the ethanolic extract of Tinospora cordifolia (TCE) as a dietary supplement in ameliorating TNP induced toxicity in Nile tilapia (Oreochromis niloticus). The fishes were exposed to environmentally relevant concentration (10 mg/L) of TNP for 14 days and the effect of TCE supplemented feed at 3 different doses (5, 10, and 15 g/kg) was studied. TCE signally increased the weight gain, specific growth rate, and decreased feed conversion ratio in fish. TCE significantly (P < 0.05) ameliorated the toxic effects caused by TNP by increasing the antioxidant (CAT, SOD, GPx) activity and decreasing the levels of serum enzymes (ALT, AST, ALP, ACP), macromolecular oxidation, excessive ROS production, and pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, INF-γ, TNF-α, PGE-2). TNP bioaccumulation and histopathological alterations in gill, liver, and kidney were also significantly alleviated by TCE supplementation. TCE perceptibly regulated the expression of heat shock proteins (HSP60, -70), MAPKs (pERK1/2, pp38), antioxidant (NRF2, Keap1, HO-1), apoptotic (p53, PDRG1), and anti-apoptotic (AKT, Bcl2) proteins in fish. Regarding disease resistance, the TCE co-treated groups showed reduced cumulative mortality and higher relative percent survival with A. hydrophila. Our results suggest that TNP-induced apoptosis is mediated by the MAPK/NRF2/Keap1 pathway and underlines the therapeutic potential of TCE in aqua-farming.