Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus.

Abstract

Methylphenidate (MPH) abuse causes neurodegeneration. The neuroprotective effects of topiramate (TPM) have been reported but its putative mechanism remains unclear. The current study evaluates the role of various doses of TPM on protection of rat hippocampal cells from MPH-induced oxidative stress and inflammation invivo. Seventy adult male rats were divided into six groups. Group 1 received normal saline (0.7mL/rat) and group 2 was injected with MPH (10mg/kg) for 21days. Groups 3, 4, 5, 6 and 7 concurrently were treated by MPH (10mg/kg) and TPM (10, 30, 50, 70 and 100mg/kg, intraperitoneally (i.p.)), respectively for 21 days. After drug administration, the open field test (OFT) was used to investigate motor activity. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. Also, the brain-derived neurotrophic factor (BDNF) level was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Cresyl violet staining of Dentate Gyrus (DG) and CA1 cell layers of the hippocampuswere also performed. MPH significantly disturbs motor activity in OFT and TPM (70 and 100mg/kg) decreased thisdisturbance. Also MPH significantly increased lipid peroxidation, mitochondrial reduced state of glutathione (GSH) level, interleukin (IL)-1β and tumour necrosis factor (TNF)-α and BDNF level in isolatedhippocampal cells. Also superoxide dismutase, glutathione peroxidase and glutathione reductase activity significantly decreased. Various doses of TPM attenuated these effects and significantly decreased MPH-induced oxidative damage, inflammation and hippocampal cell loss and increased BDNF level. This study suggests that TPM has the potential to be used as a neuroprotective agent against oxidative stress and neuroinflammation induced by frequent use of MPH.