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-1β, 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.

由于其杀菌特性，已建议将二氧化钛纳米颗粒（TNP）用于鱼场以预防或减轻细菌性疾病。不幸的是，TNP与细胞的相互作用削弱了鱼类的宿主防御能力，导致细菌攻击期间死亡率增加。本研究评估了田鼠（Tinospora cordifolia）（TCE）的乙醇提取物作为膳食补充剂改善TNP诱导的尼罗罗非鱼（Oreochromis niloticus）毒性的功效。。将鱼暴露于环境相关浓度（10 mg / L）的TNP中14天，并研究了添加3种不同剂量（5、10和15 g / kg）的TCE补充饲料的效果。TCE信号增加了鱼的增重，比生长率和饲料转化率降低。TCE显着（P <0.05）通过增加抗氧化剂（CAT，SOD，GPx）活性并降低血清酶（ALT，AST，ALP，ACP），大分子氧化，过量的ROS产生和促炎性来改善TNP的毒性作用细胞因子（IL-1β，IL-6，IL-8，INF-γ，TNF-α，PGE-2）。通过补充TCE，also，肝和肾中的TNP生物蓄积和组织病理学改变也明显减轻。TCE可以调节热休克蛋白（HSP60，-70），MAPK（pERK1 / 2，pp38），抗氧化剂（NRF2，Keap1，HO-1），凋亡（p53，PDRG1）和抗凋亡（AKT，鱼中的Bcl2）蛋白。关于抗病性，TCE的共同处理组显示出降低的累积死亡率和较高的相对存活百分比与嗜水气单。我们的结果表明，TNP诱导的凋亡是由MAPK / NRF2 / Keap1途径介导的，并强调了TCE在水产养殖中的治疗潜力。