Salek Abir, Selmi Mouna, Njim Leila, Umek Polona, Mejanelle Philippe, Moussa Fathi, Douki Wahiba, Hosni Karim, Baati Tarek
Laboratoire des Substances Naturelles, Institut National de Recherche et d'Analyse Physico-chimique, Biotechpôle Sidi Thabet 2020 Tunisia
Service d'Anatomie Pathologique, EPS Fattouma Bourguiba de Monastir, Faculté de Médecine de Monastir, Université de Monastir 5000 Monastir Tunisia.
Nanoscale Adv. 2023 Apr 25;5(11):2950-2962. doi: 10.1039/d2na00874b. eCollection 2023 May 30.
Voluntary drug intoxication is mainly due to drug overdose or the interaction of several drugs. Coma and its associated complications such as hypoventilation, aspiration pneumopathy, and heart rhythm disorders are the main hallmarks of drug intoxication. Conventional detoxification treatments, including gastric lavage or vomiting, administration of ipecac or activated charcoal (CH), and the use of antidotes, have proven to be inefficient and are generally associated with severe adverse effects. To overcome these limitations, titanate nanotubes (TiNTs) are proposed as an efficient emerging detoxifying agent because of their tubular shape and high adsorption capacity. In the present study, the detoxifying ability of TiNTs was evaluated on paracetamol (PR)-intoxicated rats. Results indicate that the loading ability of PR into TiNTs (70%) was significantly higher than that recorded for CH (38.6%). In simulated intestinal medium, TiNTs showed a controlled drug release of less than 10% after 72 h of incubation. In PR-intoxicated rats, TiNTs treatment resulted in a 64% decrease of PR after 4 h of poisoning 40% for CH. Concomitantly, TiNTs efficiently reduced PR absorption by 90% after 24 h of poisoning, attenuated the elevated levels of biochemical markers (, alanine aminotransferase, aspartate aminotransferase, creatinine, and TNF-α) and mitigated oxidative stress by increasing the activity of superoxide dismutase and reducing the oxidized glutathione/total glutathione ratio, suggesting a histoprotective effect of TiNTs against paracetamol-induced toxicity in rats. In addition to their safety and high stability in the entire gastro-intestinal tract, biodistribution analysis revealed that TiNTs exhibited low intestinal absorption owing to their large cluster size of compact aggregate nanomaterials across the intestinal villi hindering the absorption of paracetamol. Collectively, these data provide a new and promising solution for detoxification. TiNTs are expected to have great potential for the treatment of voluntary and accidental intoxication in emergency care.
自愿性药物中毒主要是由于药物过量或多种药物相互作用所致。昏迷及其相关并发症，如通气不足、吸入性肺炎和心律失常，是药物中毒的主要特征。传统的解毒治疗方法，包括洗胃或催吐、服用吐根糖浆或活性炭（CH）以及使用解毒剂，已被证明效率低下，且通常伴有严重的不良反应。为克服这些局限性，钛酸盐纳米管（TiNTs）因其管状形状和高吸附能力，被提议作为一种高效的新型解毒剂。在本研究中，对乙酰氨基酚（PR）中毒大鼠评估了TiNTs的解毒能力。结果表明，PR在TiNTs中的负载能力（70%）显著高于CH（38.6%）。在模拟肠道介质中，TiNTs在孵育72小时后显示出低于10%的可控药物释放。在PR中毒大鼠中，TiNTs治疗在中毒4小时后使PR含量降低了64%，而CH为40%。同时，TiNTs在中毒24小时后有效减少了90%的PR吸收，降低了生化标志物（丙氨酸转氨酶、天冬氨酸转氨酶、肌酐和TNF-α）的升高水平，并通过提高超氧化物歧化酶的活性和降低氧化型谷胱甘肽/总谷胱甘肽比值减轻了氧化应激，表明TiNTs对大鼠扑热息痛诱导的毒性具有组织保护作用。除了在整个胃肠道中的安全性和高稳定性外，生物分布分析表明，由于TiNTs作为紧密聚集的纳米材料具有较大的簇尺寸，跨越肠绒毛阻碍了扑热息痛的吸收，因此其肠道吸收较低。总体而言，这些数据为解毒提供了一种新的、有前景的解决方案。TiNTs有望在急诊护理中治疗自愿性和意外中毒方面具有巨大潜力。
