Cinepazide maleate protects PC12 cells against oxygen-glucose deprivation-induced injury.

Jun Zhao, Ya Bai, Chen Zhang, Xiao Zhang, Yun-Xia Zhang, Jing Chen, Lize Xiong, Ming Shi, Gang Zhao
Author Information
  1. Jun Zhao: Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle-Xi Road, Xi'an, 710032, China, cczhaojuncc@gmail.com.

Abstract

Our previous study showed that cinepazide maleate (CM) was as effective and safe as mildronate in the treatment of acute ischemic stroke in a randomized, double-blind, active-controlled phase II multicenter trial, but underlying mechanism(s) is not well understood. As an extending study, here we demonstrated that CM could protect neuronal cells by affecting mitochondrial functions. PC12 cells were exposed to 2.5 h oxygen-glucose deprivation (OGD) followed by a 24 h reoxygenation, and then treated with different concentrations (1, 10, 100 μM) of CM. Among various concentrations, 10 μM CM exhibited most significant protection on PC12 cells against OGD injury. CM was found to suppress OGD-induced oxidative stress, as supported by its capability of reducing intracellular reactive oxygen species and malondialdehyde production and enhancing superoxide dismutase activity. Importantly, our results showed that CM could preserve mitochondrial functions, as revealed by its capability of stabilizing mitochondrial membrane potential, improving OGD-induced suppression of mitochondrial respiratory complex activities and enhancing ATP production. In summary, our present study provides the first evidence that CM can protect neuronal cells against OGD injury by preserving mitochondrial functions.

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MeSH Term

Animals
Glucose
Mitochondria
Neuroprotective Agents
Oxidative Stress
Oxygen
PC12 Cells
Piperazines
Rats

Chemicals

Neuroprotective Agents
Piperazines
cinepazide
Glucose
Oxygen