Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt.; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Toxicol Appl Pharmacol. 2019 Feb 15;365:41-50. doi: 10.1016/j.taap.2018.12.015. Epub 2018 Dec 25.
Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancer patients treated with oxalipatin based chemotherapy.
The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatin neurotoxicity in colorectal cancer patients with emphasis on the redox (Nrf-2, MDA), inflammatory (NF-κB, TNF-α), and apoptotic (caspase-3) parameters.
In this pilot study, 65 patients were recruited using a prospective randomized controlled study design and enrolled randomly into two arms; Arm A, 31 patients received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B, 34 patients received FOLFOX-6 regimen and daily oral L-carnosine (500 mg) along the treatment period. Patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC version 4).
The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal. In arm B, the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%) and TNF-α (36.6%); this anti-inflammatory effect entailed also its anti-oxidative and anti-apoptotic effects, thus MDA level (51.8%) and caspase-3 activity (49%) were also reduced, whereas Nrf-2 was increased (38.7%) as compared to Arm A. In both arms a significant correlation was only evident between TNF-α and the neuropathy grading score (P < .03); the correlation analysis was significantly positive between NF-κB and both Nrf-2 and caspase 3.
L-Carnosine exerted a neuroprotective effect against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients by targeting Nrf-2 and NF-κB pathways.
奥沙利铂为基础的化疗会引起外周神经病变，这是癌症患者常见的副作用。
本研究旨在探讨左旋肉碱（L-carnosine）对结直肠癌患者奥沙利铂急性神经毒性的潜在预防作用，重点关注氧化还原（Nrf-2、MDA）、炎症（NF-κB、TNF-α）和凋亡（caspase-3）参数。
本研究采用前瞻性随机对照研究设计，共招募 65 例患者，随机分为两组；A 组 31 例患者接受 FOLFOX-6 方案（奥沙利铂、5FU 和亚叶酸钙），B 组 34 例患者接受 FOLFOX-6 方案加每日口服 L-carnosine（500mg）治疗。患者随访 3 个月，然后根据国家癌症研究所不良事件通用术语标准（NCI-CTC 版本 4）分析两组的神经病变发生率/分级和任何其他毒性。
B 组的神经病变分级评估显示，17 例（56.7%）患者发生 1 级，1 例（3.3%）患者发生 2 级，而 12 例（40%）患者正常；A 组则有 11 例（35.5%）患者发生 1 级，19 例（61.3%）患者发生 2 级，1 例（3.2%）患者正常。B 组中，L-carnosine 的添加显著降低了 NF-κB（27%）和 TNF-α（36.6%）的水平/活性；这种抗炎作用还带来了抗氧化和抗凋亡作用，因此 MDA 水平（51.8%）和 caspase-3 活性（49%）也降低了，而 Nrf-2 则增加了（38.7%）。在两组中，仅 TNF-α与神经病变分级评分之间存在显著相关性（P<0.03）；NF-κB 与 Nrf-2 和 caspase-3 之间的相关性分析呈显著正相关。
L-carnosine 通过靶向 Nrf-2 和 NF-κB 通路，对结直肠癌患者奥沙利铂引起的周围神经病变发挥神经保护作用。
