Role of apocynin in alleviation of oxidative stress and neuronal autophagy after traumatic brain injury by activating the PI3K/Akt/Nrf2 pathway in rats

INTRODUCTION: The study aimed to determine whether apocynin (APO) can protect neurons in rats with traumatic brain injury (TBI) by activating the PI3K/Akt/Nrf2 pathway, acting as an antioxidant, and suppressing autophagy. MATERIAL AND METHODS: Ninety male Sprague-Dawley rats (220-260 g) were randomly assigned to three groups: a control group with a sham operation, a group with TBI, and a group that received APO following TBI. Saline and APO were intraperitoneally administered for three consecutive days based on the aforementioned groups. Ten rats from each group underwent behavioral assessment, and neuronal morphology was evaluated using HE staining. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were measured using the xanthine oxidase method, barbiturate sulfate method, and dithiobenzoic acid condensation method, respectively. Rat hippocampal tissue was extracted, and Western blotting was performed to assess the expression of autophagy-related proteins as well as signaling pathway-related proteins. RESULTS: Compared to the TBI group, those treated with APO showed reduced cognitive deficits and neural damage resulting from TBI. The degree of neuronal damage in the treatment group was statistically significantly reduced. Treatment with APO in rats with TBI significantly elevated the hippocampal levels of GSH and SOD and significantly reduced the production of MDA and reactive oxygen species (ROS). Additionally, APO alleviated hippocampal neuronal autophagy by reducing LC3II and Beclin-1 expression levels. Regarding of the signaling pathway, APO elevated the expression of p-PI3K, p-Akt, Nrf2, and HO-1 in the hippocampus of TBI rats. CONCLUSIONS: In conclusion, APO represents a potential treatment for TBI due to its antioxidative and autophagy-reducing properties via the PI3K/Akt/Nrf2 pathway, thereby preventing hippocampal injury after brain trauma.