Pentoxifylline Protects Against Hippocampal Damage and Memory Impairment Induced by Trimethyltin

Abstract

Background: Trimethyltin (TMT) is a toxic agent that causes oxidative stress, a laboratory model for inducing hippocampal injuries. Pentoxifylline (PTX) inhibits phosphodiesterase, inflammation and oxidative stress. This study evaluated the neuroprotective effects of PTX on injuries induced by TMT in the hippocampus. Methods: Sixty male Wistar rats were divided into five groups of 12 each. Group 1 received normal saline while Group 2 received a single dose of TMT (8 mg/kg). The other four groups received TMT at 8 mg/kg plus 60, 100 or 120 mg/kg PTX twice daily for six consecutive days. The rats’ working and reference memory were investigated, using radial arm maze tasks. At the end of the experiments, the rats’ brains were removed and processed for histological study of the hippocampus. Results: The TMT treatment prolonged the four baited arms tasks (P<0.001), while the PTX treatment at 60, 100 or 120 mg/kg significantly reduced the effects of TMT on the spatial memory (P<0.01). The working and reference memory errors significantly increased in the TMT group compared to the controls (P<0.001) while the PTX treatment significantly reduced the TMT effect (P<0.001). Also, TMT increased the number of pyknotic cells in the hippocampus (P<0.001), while PTX significantly decreased the mean number of pyknotic cells (P<0.05). Conclusion: The findings suggest that PTX can protect against the memory deficit and deleterious effects on rat hippocampus induced by TMT neurotoxicity. Thus, PTX is likely to be a potential agent to prevent against the neurotoxicity induced by TMT.

Keywords

• hippocampus
• neurotoxicity
• pyknotic cells
• neurodegeneration
• tmt
• spatial memory