흰쥐 뇌에서의 Lipopolysaccharide-유도 산화적 스트레스에 대한 OQ21과 Melatonin의 작용

• 영문명: Effect of OQ21 and Melatonin on Lipopolysaccharide-Induced Oxidative Stress in Rat Brain
• 발행기관: 대한약학회
• 저자명: 배미경(Mee Kyung Bae) 최신규(Shinkyu Choi) 고문정(Moon Jeong Ko) 하헌주(Hun Joo Ha) 김화정(Hwa Jung Kim)
• 간행물 정보: 『약학회지』제49권 제4호 (2005년), 347~354쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2005.08.31

영문 초록

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 com- pound 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 pro- duced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intracellular 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 6 hr 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, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one, produced no significant RO S 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.

키워드

lipopolysaccharide nitric oxide synthase guanylyl cyclase oxidative stress rat brain