Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
J Pharm Pharmacol. 2019 May;71(5):797-805. doi: 10.1111/jphp.13047. Epub 2018 Dec 10.
The role of nuclear factor-2 erythroid related factor-2 (Nrf2) activator, berberine (BBR), has been established in rat model of streptozotocin induced diabetic neuropathy. Around 30-40% of cancer patients, on paclitaxel (PTX) chemotherapy develop peripheral neuropathy. The present study was contemplated with the aim of establishing the neuropathy preventive role of BBR, in paclitaxel induced peripheral neuropathy model in rats.
A total of 30 Wistar rats were divided into five groups as follows: Group I: dimethyl sulfoxide; Group II: PTX+ 0.9% NaCl; Group III: Amitriptyline (ATL) + PTX; Group IV: BBR (10 mg/kg) + PTX and Group V: BBR (20 mg/kg) + PTX. Animals were assessed for tail flick latency, tail cold allodynia latency, histopathological scores, oxidative stress parameters, and mRNA expression of the Nrf2 gene in the sciatic nerve.
Berberine significantly increased the tail flick and tail cold allodynia latencies and significantly decreased the histopathological score. BBR reduced oxidative stress by significantly decreasing the lipid peroxidation, increasing the superoxide dismutase and reduced glutathione levels in the sciatic nerve. BBR also increased the mRNA expression of Nrf2 gene in rat sciatic nerve.
All of these results showed the neuropathy preventing role of BBR in PTX induced neuropathy pain model in rats.
核因子-2 红细胞相关因子-2(Nrf2)激活剂小檗碱(BBR)在链脲佐菌素诱导的糖尿病周围神经病变大鼠模型中已得到证实。约 30-40%的癌症患者在接受紫杉醇(PTX)化疗后会出现周围神经病变。本研究旨在确定 BBR 在紫杉醇诱导的大鼠周围神经病变模型中的神经病变预防作用。
将 30 只 Wistar 大鼠分为五组:I 组:二甲基亚砜;II 组:PTX+0.9%NaCl;III 组:阿米替林(ATL)+PTX;IV 组:BBR(10mg/kg)+PTX;V 组:BBR(20mg/kg)+PTX。评估动物的尾巴拍打潜伏期、尾巴冷感觉过敏潜伏期、组织病理学评分、氧化应激参数以及坐骨神经中 Nrf2 基因的 mRNA 表达。
BBR 显著延长了尾巴拍打和尾巴冷感觉过敏潜伏期,显著降低了组织病理学评分。BBR 通过显著降低坐骨神经中的脂质过氧化、增加超氧化物歧化酶和还原型谷胱甘肽水平来减少氧化应激。BBR 还增加了大鼠坐骨神经中 Nrf2 基因的 mRNA 表达。
所有这些结果均表明 BBR 在 PTX 诱导的周围神经病变疼痛大鼠模型中具有预防神经病变的作用。