MK-2206 dihydrochloride ameliorates the neuronal function in spinal cord injured rats by reducing oxidative stress and modulating the PI3K/Akt pathway.

Abstract

INTRODUCTION: Spinal cord injury (SCI) is one of the major causes of paralysis and physical inability, and its management remains a challenge. The present study evaluated the effect of MK-2206 dihydrochloride in rats with SCI. MATERIAL AND METHODS: An impactor device was used to induce SCI, which was treated with MK-2206 12 mg/kg, s.c., daily for 10 days. The effect of MK-2206 on SCI was determined by estimating the locomotor function, inflammatory mediators, and oxidative stress parameters in all groups of rats. Western blot assay was performed to estimate the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) protein in the spinal tissue of SCI rats. Moreover, the effect of MK-2206 on the apoptosis of spinal tissue of SCI rats was assessed. RESULTS: Study data suggest that treatment with MK-2206 reverses the alteration in the neuronal function in SCI rats. Cytokines and oxidative stress were observed to be ameliorated in the MK-2206-treated group compared to the SCI group. Moreover, treatment with MK-2206 attenuated PI3K and Akt protein expression in the spinal tissue of SCI rats. Treatment with MK-2206 significantly reduced the apoptosis of spinal tissue in SCI rats. CONCLUSIONS: The data suggest that treatment with MK-2206 prevents injury to the neuronal tissue in SCI rats by modulating the PI3k/Akt pathway.