Effect of curcumin on lidocaine-induced nerve injury in rats: the role of Akt and ERK1/2 signaling pathway

Abstract

Objective To evaluate the effect of curcumin on lidocaine-induced nerve injury and the role of protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in rats. Methods Eighty SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were divided into 8 groups (n=10 each) using a random number table method: control group(group C), sham operation group(group S), lidocaine group (group L), dimethyl sulfoxide (DMSO) group, low-dose curcumin group (group CL), high-dose curcumin group (group CH), curcumin plus ERK inhibitor PD98059 group (group P) and curcumin plus Akt inhibitor MK-2206 group (group M). The model of nerve injury was established by injecting 2% lidocaine 10 μl via the catheter in anesthetized rats in the other six groups except for C and S groups.Drugs were injected through a microcatheter for 14 consecutive days starting from 3rd day after IT catheterization as follows: DMSO 10 μl, curcumin 100 μg/10 μl and curcumin 500 μg/10 μl were injected once a day in D, CL and CH groups, respectively; curcumin 500 μg/10 μl was injected once a day, and D98059 10 μg and MK-2206 12 μg (in 5 μl DMSO) were intraperitoneally injected once a week in P and M groups, respectively.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal threshold (TWL) on the operated side were measured on 1 day before IT catheterization, before administration on 3rd day after IT catheterization, and on 14th day after administration.The spinal cord was removed on 1st day after the end of administration for determination of the expression of ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), Akt, phosphorylated Akt (p-Akt), c-fos, Bcl-2 and Bax (by Western blot) and expression of ERK1/2 and Akt mRNA (by real-time polymerase chain reaction). Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, the expression of ERK1/2 protein and mRNA, p-ERK1/2, c-fos, Akt protein and mRNA, p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group L (P<0.05). Compared with group L, the MWT was significantly increased, and the TWL was prolonged in CL, CH, P and M groups, the expression of p-ERK1/2, c-fos, p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in CL and CH groups, the expression of p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in group P, and the the expression of p-ERK1/2 and c-fos was up-regulated in group M (P<0.05). Compared with group CH, the MWT was significantly decreased, and the TWL was shortened in P and M groups, the expression of p-ERK1/2 and c-fos was down-regulated in group P, and the expression of p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group M (P<0.05). Conclusion Curcumin can reduce lidocaine-induced nerve injury, and the mechanism may be partly related to enhancing the activity of Akt and ERK1/2 signaling pathway in rats. Key words: Curcumin; Lidocaine; Drug-related side effects and adverse reactions; MAP kinase signaling system