Background and Aim: The most frequent kind of partial epilepsy leading to recurrent spontaneous seizures and neural degeneration, mainly in the hippocampus, is the temporal lobe epilepsy (TLE). Oxidative stress and apoptosis play pivotal roles in triggering and developing repeated seizures as well as neuronal death following seizures. Anticonvulsant, antioxidative, and neuroprotective properties of alpha-pinene (APN) have been reported in some experimental models of neurodegenerative diseases. However, its neuroprotective efficacy in a rat model of TLE induced by kainic acid (KA) has remained unexplored. We aimed to find out the outcomes of an APN pretreatment for two weeks on epileptic behaviors, neuronal damage, oxidative stress, and apoptosis in a rat model of TLE. Methods: Male Wistar rats (n = 70) were randomly distributed into five experimental groups as follows (1) Control-vehicle; (2) Dimethyl sulfoxide (DMSO 5%)-pretreated + sham; (3) APN (50 mg/kg)-pretreated + sham; (4) kainic acid (KA), and (5) APN (50 mg/kg)-pretreated + KA groups. TLE was induced by unilaterally intracerebroventricular microinjection of KA. APN pretreatment at a dose of 50 mg/kg/day was intraperitoneally performed two weeks before induction of TLE. The neuronal cell loss in the CA3 region of the hippocampus was evaluated by Nissl staining. The hippocampal levels of oxidative stress markers, such as malondialdehyde, total antioxidant capacity and total oxidant status were measured. The protein levels of Bax, Bcl-2, and c-Jun N-terminal kinase (JNK) were also assessed using by western blotting method. Results: The results revealed that APN pretreatment alleviated epileptic seizures, diminished oxidative stress indicators prevented neuronal death in the CA3 region and blocked the mitochondrial apoptotic pathway via decreasing Bax and raising Bcl-2 protein levels in the hippocampus at least partly through inhibiting JNK activity. Significance: These findings suggest that APN pretreatment mitigates KA-induced seizures by blocking neuronal damage, oxidative stress, apoptosis, and attenuation of the JNK activity in the hippocampus. Conclusion: These findings suggest that APN pretreatment mitigates KA-induced seizures through blocking neuronal damage, oxidative stress, apoptosis, and attenuation of the JNK activity in the hippocampus.
