Peripheral neurotoxicity often occurs in patients receiving parenteral polymyxin therapy (i.e., colistin methanesulfonate or polymyxin B). The present study aimed to investigate the protective effect of curcumin on colistin-induced peripheral neurotoxicity using a murine model. Female C57BL/6 mice (n = 10 in each group) were randomly divided into the following: (1) control group (saline), (2) curcumin only group (200 mg/kg/day; orally), (3) colistin only group (18 mg/kg/day; i.p.), (4) colistin (18 mg/kg/day) plus curcumin 50 mg/kg/day group, (5) colistin (18 mg/kg/day) plus curcumin 100 mg/kg/day group, (6) colistin (18 mg/kg/day) plus curcumin 200 mg/kg/day group; all mice were treated for 7 days. Orally applied curcumin was detected in the brain, cerebellum, and sciatic nerve. Co-administration of oral curcumin markedly improved colistin-induced impaired sensory and motor dysfunctions in a dose-dependent manner. Curcumin supplementation at 100 and 200 mg/kg significantly decreased lipid peroxidation and upregulated catalase (CAT) and superoxide dismutase (SOD) activities, ATP levels, and Na+/K+-ATPase activity in sciatic nerve tissue, compared to the colistin alone group. Curcumin supplementation at 200 mg/kg upregulated the levels of AKT, NGF, mTOR, Nrf2, and HO-1 mRNA and concomitantly downregulated Bax, caspases-3, and -9 mRNA; it also decreased caspase-3 and caspase-9 activity. In summary, for the first time, our study reveals that the protective effect of oral curcumin on colistin induced peripheral neurotoxicity is associated with the activation of NGF/Akt and Nrf2/HO-1 pathways and inhibition of oxidative stress. This study highlights the potential clinical application of curcumin as an oral neuroprotective agent coadministered during colistin therapy.

中文翻译：

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姜黄素减轻小鼠共利斯汀诱导的周围神经毒性。

接受肠外多粘菌素治疗（例如粘菌素甲磺酸盐或多粘菌素B）的患者经常发生周围神经毒性。本研究旨在使用鼠模型研究姜黄素对大肠菌素诱导的周围神经毒性的保护作用。将雌性C57BL / 6小鼠（每组10只）随机分为以下几组：（1）对照组（盐水），（2）仅姜黄素组（200 mg / kg /天；口服），（3）大肠菌素仅一组（18 mg / kg /天; ip），（4）大肠菌素（18 mg / kg /天）加姜黄素50 mg / kg /天组，（5）大肠菌素（18 mg / kg /天）加姜黄素100毫克/千克/天组，（6）大肠菌素（18毫克/千克/天）加姜黄素200毫克/千克/天组；所有小鼠均治疗7天。在大脑，小脑和坐骨神经中检测到口服姜黄素。口服姜黄素的共同给药以剂量依赖性方式显着改善大肠菌素诱导的感觉和运动功能障碍。与单独粘杆菌素组相比，以100和200 mg / kg补充姜黄素可显着降低坐骨神经组织中的脂质过氧化和上调过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性，ATP水平以及Na + / K + -ATPase活性。以200 mg / kg补充姜黄素可上调AKT，NGF，mTOR，Nrf2和HO-1 mRNA的水平，并同时下调Bax，caspases-3和-9 mRNA的水平。它也降低了caspase-3和caspase-9的活性。总而言之，我们的研究首次揭示口服姜黄素对粘菌素诱导的周围神经毒性的保护作用与NGF / Akt和Nrf2 / HO-1途径的激活以及氧化应激的抑制有关。