title: Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats.
abstract: Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats. Forty-two rats were equally divided into 7 groups. The first and second groups were used as untreated and sham controls, respectively. The third (DEX4) and fourth (DEX40) groups received 4mg/kg and 40mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cerebral ischemia. The fifth, sixth and seventh groups are used to represent cerebral ischemia, cerebral ischemia+DEX4, and cerebral ischemia+DEX40, respectively. DEX was intraperitoneally given to the DEX groups at the 3rd, 24th and 48th hour. Brain and erythrocyte lipid peroxidation (MDA) levels and plasma IL-1β and TNF-α levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values in the brain and erythrocyte of the cerebral ischemia group were increased by the DEX treatments, although PARP, and the caspase 3 and 9 expressions in the brain were further decreased. Conversely, the cerebral ischemia-induced decrease in the liver vitamin A, vitamin E, GSH, and GSH-Px were further decreased by the DEX treatments, although MDA level, PARP, and caspase 3 and 9 expressions were further increased by the DEX treatments. In conclusion, DEX induced protective effects against cerebral ischemia-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production. However, both doses of DEX induced oxidative toxicity and apoptotic effects in the rats' livers.
authors.affiliation: Unit of Microbiology, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Akpınar
authors.affiliation: Neuroscience Research Center, University of Suleyman Demirel, Isparta, Turkey. Electronic address: mustafanaziroglu@sdu.edu.tr.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.affiliation: Unit of Anesthesiology and Reanimation, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Akpınar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000633:toxicity; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D008315:Malondialdehyde; D020927:Dexmedetomidine; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D020170:Caspase 1; D005978:Glutathione
keywords: Brain; Cerebral ischemia; Cytokine; Dexmedetomidine; Liver; Oxidative stress