Effect of Piracetam on Brain Oxidative Stress and Tissue Damage Following Toluene Exposure in Rats

In this study, the effect of the nootropic drug piracetam on brain oxidative stress and histopathological changes in brain, liver and kidney following exposure to toluene in rats was examined. Piracetam (150 or 300 mg/kg, subcutaneously, daily) was given along with toluene (500 mg/kg, intraperitoneally, daily) for one week. The brain content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) in brain homogenates were determined. Histopathology of the brain, liver and kidney and brain Bax immunohistochemistry were performed. Results showed that exposure to toluene resulted in increased brain lipid peroxidation (MDA) and NO along with decreased reduced glutathione. Toluene also inhibited PON-1, and BChE activities. The administration of piracetam had no significant effect on brain lipid peroxidation. The level of reduced glutathione was unchanged by piracetam but PON1 activity was increased by the lower dose of the drug. Piracetam showed no significant effect on BChE activity in toluene treated rats. Histopathological examination of the brain of toluene only treated rats showed degenerated neurons in cerebral cortex, marked neuronal vacuolation in hippocampus and focal hemorrhage. Bax 3 immunohistochemical staining showed cytoplasmic reactivity in degenerated neurons. Rats given piracetam showed decreased cortical cellularity, increased number of degenerated neurons and increased BAX staining. The higher dose of the drug caused sinusoidal hemorrhage and intertubular hemorrhage in kidney. Collectively, these results indicate that treatment with piracetam wan not able to decrease neuronal damage in rats exposed to toluene.