Brain Research Bulletin 130 (2017) 1–9 Contents lists available at ScienceDirect Brain Research Bulletin journal homepage: www.elsevier.com/locate/brainresbull 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 Orhan Akpınar a , Mustafa Nazıro˘ glu b,∗ , Hatice Akpınar c a Unit of Microbiology, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey b Neuroscience Research Center, University of Suleyman Demirel, Isparta, Turkey c Unit of Anesthesiology and Reanimation, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey a r t i c l e i n f o Article history: Received 24 August 2016 Accepted 9 December 2016 Available online 19 December 2016 Keywords: Brain Cerebral ischemia Cytokine Dexmedetomidine Liver Oxidative stress a b s t r a c t Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modu- lated 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 4 mg/kg and 40 mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cere- bral 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-1 and TNF- levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glu- tathione 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. © 2016 Elsevier Inc. All rights reserved. 1. Introduction Cerebral ischemia-induced injury is a major cause of death and disability in adults and newborns. The long-term outcome for the brain in cerebral ischemia-induced injury includes neuronal diseases such as cerebral palsy, epilepsy, and mental retarda- tion (Lynch and Nelson, 2001). Tissue damage occurs in ischemia Abbreviations: DEX, dexmedetomidine; GSH, reduced glutathione; GSH-Px, glu- tathione peroxidase; IL-1, interleukin-1; ISC, ischemia; MDA, malondialdehyde; NF-kB, nuclear factor kappa B; PARP, poly (ADP-ribose) polymerase; ROS, reactive oxygen species; TBAR, thiobarbituric-acid; TNF-, tumor necrosis factor-alpha. ∗ Corresponding author at: Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey. E-mail address: mustafanaziroglu@sdu.edu.tr (M. Nazıro˘ glu). through energy depletion, accumulation of toxic metabolic prod- ucts and activation of phospholipase (Cai et al., 2014; Kumar et al., 2014). Reperfusion leads to further neuronal damage through generating reactive oxygen species (ROS). In addition to a poor enzymatic antioxidant defense system, brain and erythrocytes have a high rate of oxygen consumption and a rich content of polyun- saturated fatty acids (PUFAs). Because of the three reasons (their high rate of oxygen consumption, high content of PUFAs and poor enzymatic antioxidant scavenger system), the brain and erythro- cytes exhibit increased vulnerability to ischemia-induced oxidative stress (Nazıro˘ glu, 2011; Yang et al., 2014). The liver is also essen- tial for detoxification of ROS and cytokine productions. Hence, liver is also one of the main defense systems against ischemia-induced excessive production of ROS and inflammation in the body (Gong et al., 2012; Gul et al., 2015). http://dx.doi.org/10.1016/j.brainresbull.2016.12.005 0361-9230/© 2016 Elsevier Inc. All rights reserved.