title: Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.
abstract: 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-1α) 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.
authors.affiliation: Medical School, Alborz University of Medical Sciences, Alborz, Iran. lkhalaj@yahoo.com
authors.forename: Leila
authors.initials: L
authors.lastname: Khalaj
authors.forename: Sara Chavoshi
authors.initials: SC
authors.lastname: Nejad
authors.forename: Marzieh
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Sadaf Sarraf
authors.initials: SS
authors.lastname: Zadeh
authors.forename: Marieh Hossein
authors.initials: MH
authors.lastname: Pour
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Ghorbangol
authors.initials: G
authors.lastname: Ashabi
authors.forename: Shabnam Zeighamy
authors.initials: SZ
authors.lastname: Alamdary
authors.forename: Elham
authors.initials: E
authors.lastname: Samami
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D015248:Gemfibrozil / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000009:adverse effects; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D015248:Gemfibrozil
keywords: (NQO)-1; AIF; Acute restraint Stress; Antioxidant defense system; Apoptosis; CAT; DAB; EAE; GPx; GSH; Gemfibrozil; H&E; HO-1; HPA; I/R; IAPs; MCAO; MDA; MS; Mitochondrion; NAD(P)H quinone oxidoreductase-1; NBT; NRF; Nrf-2; PBS; PGC-1 related coactivator; PGC-1α; PPAR; PRC; ROS; SOCS; SOD; TBA; TBI; TFAM; UCP2; apoptosis-inducing factor; catalase; diaminobenzidine; experimental autoimmune encephalomyelitis; glutathione; glutathione peroxidase; hematoxylin–eosin; heme oxygenase-1; hypothalamic–pituitary–adrenal; inhibitors of apoptosis; ischemia-reperfusion; malondialdehyde; middle cerebral artery occlusion; mitochondrial transcription factor A; multiple sclerosis; nitroblue tetrazolium; nuclear factor erythroid-related factor-2; nuclear respiratory factor; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor coactivator-1α; phosphate-buffered saline; reactive oxygen species; superoxide dismutase; suppression of cytokine signaling; thiobarbituric acid; traumatic brain injury; uncoupling protein 2