The protective effect of fasudil against acrylamide-induced cytotoxicity in PC12 cells

Abstract

Acrylamide (ACR), a vinyl monomer that has multiple chemical and industrial applications, is a neurotoxic agent in human and animal. Fasudil is a potent Rho-kinase inhibitor which exhibits neuroprotective effects in some neuronal degenerative disorders. In this study, the potential protective effect of Fasudil on ACR-induced cytotoxicity in PC12 cells was evaluated. Our results showed that ACR increased the level of intracellular reactive oxygen species (ROS) and consequently upregulated the Bax/Bcl-2 ratio and significantly elevated the level of caspase-3 and 9 proteins in PC12 cells. Interestingly, pretreatment with Fasudil protected PC12 cells against ACR-induced toxicity mainly through the reduction of ROS production and modulation of proteins which involved in apoptosis pathway. Fasudil down-regulated the Bax/Bcl-2 ratio and the levels of caspase-3 and 9 proteins in cells exposed to ACR. In conclusion, the neuroprotective effect of Fasudil against ACR-induced toxicity in PC12 cells appears to be mediated through inhibition of ROS production and modulation of apoptosis.