Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus

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• 作者：Leila Khalaj ; Sara Chavoshi Nejad ; Marzieh Mohammadi ; Sadaf Sarraf Zadeh ; Marieh Hossein Pour ; Abolhassan Ahmadiani ; Fariba Khodagholi ; Ghorbangol Ashabi ; Shabnam Zeighamy Alamdary ; Elham Samami
• 关键词：AIF ; apoptosis-inducing factor ; CAT ; catalase ; DAB ; diaminobenzidine ; EAE ; experimental autoimmune encephalomyelitis ; GPx ; glutathione peroxidase ; GSH ; glutathione ; H&E ; hematoxylin&ndash ; eosin ; HO-1 ; heme oxygenase-1 ; HPA ; hypothalamic&ndash ; pituitary&nd
• 刊名：Brain Research
• 出版年：2013
• 出版时间：21 August, 2013
• 年：2013
• 卷：1527
• 期：Complete
• 页码：117-130
• 全文大小：1422 K

文摘

Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1¦Á) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts.