Valproic acid-mediated inhibition of trimethyltin-induced deficits in memory and learning in the rat does not directly depend on its anti-oxidant properties

Background: Trimethyltin (TMT) acts as a potent neurotoxic compound especially for the hippocampus. The effects of valproic acid (VPA) on TMT-induced learning and memory deficits were investigated.

Methods: The rats were divided into: (1) control, (2) TMT, (3) TMT-VPA 1, (4) TMT-VPA 5, (5) TMT-VPA 10. TMT was injected as a single dose (12 mg/kg, ip) in groups 2-5. The animals of groups 3-5 were treated by 1, 5, and 10 mg/kg of VPA for 2 weeks. Learning and memory deficits were assessed by Morris water maze (MWM) and passive avoidance (PA) tests. The markers of oxidative stress mainly malondialdehyde (MDA) level and total thiol content were measured in the brain regions.

Results: In MWM test, escape latency and traveled path in the TMT group were higher than control (p < 0.05 and p < 0.01). Treatment by 1, 5, and 10 mg/kg of VPA reduced escape latency and traveled path (p < 0.01-p < 0.001). In PA test, the time latency to enter the dark compartment in TMT group was lower than control group (p < 0.01). Treatment by 5 and 10 mg/kg of VPA increased the time latency (p < 0.05-p < 0.001). MDA concentration in hippocampal tissues of TMT group was higher while, total thiol content was lower than control ones (p < 0.05). Pretreatment with 10 mg/kg of VPA decreased the MDA level while, increased total thiol content (p < 0.01).

Conclusions: The results of present study showed that VPA attenuates TMT-induced memory deficits. Protective effects against brain tissues oxidative damage might have a role in the beneficial effects of VPA.