Leila Khalaj
Alborz University of Medical Sciences, Iran
Posters & Accepted Abstracts: Neurochem Neuropharm
Two important pathophysiological mechanisms involved in cerebral ischemia are oxidative stress and inflammation. During pathological conditions such as brain ischemia, the ability of free radicals production is believed to be greater than their elimination by endogenous antioxidant systems, so brain is highly injured due to the oxidative and neuroinflammatory processes. Fibrates as peroxisome proliferator-activated receptor (PPAR)-�± ligands, are reported to have antioxidant and antiinflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia-reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid-related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-�±, nuclear factor-�ºB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti-hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sexdependent neuroprotective/neurodegenerative potential.
Leila Khalaj has completed her PharmD and her PhD from Shahid Beheshti University of Medical Sciences. She has done her Post-doctoral studies in Neuroscience Research Center of Shahid Beheshti University and her sabbatical leave in Eskitis Institute for Cell and Molecular Therapies, Brisbane, Australia. She has published more than 14 papers in reputed journals, and currently she is an Assistant Professor in Alborz University of Medical Sciences, Alborz, Iran.
