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Effect of OQ21 and Melatonin on Lipopolysaccharide-Induced Oxidative Stress in Rat Brain  

Bae Mee Kyung (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Choi Shinkyu (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Ko Moon-Jeong (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Ha Hun-Joo (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Kim Hwa-Jung (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Publication Information
YAKHAK HOEJI / v.49, no.4, 2005 , pp. 347-354 More about this Journal
Abstract
Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.
Keywords
lipopolysaccharide; nitric oxide synthase; guanylyl cyclase; oxidative stress; rat brain;
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