title: N(1)-(quinolin-2-ylmethyl)butane-1,4-diamine, a polyamine analogue, attenuated injury in in vitro and in vivo models of cerebral ischemia.
abstract: It has been widely recognized that glutamate (Glu)-induced cytotoxicity, intracellular calcium overload and excessive free radical production are the key players in the development and progression of ischemic brain injury. Since MK-801, an antagonist of N-methyl-d-aspartate (NMDA) receptor, showed many adverse reactions that hampered its clinical applications, development of safe and effective agent for the treatment of cerebral ischemia is eagerly required. This study was to investigate the effects of N(1)-(quinolin-2-ylmethyl)butane-1,4-diamine (QMA), a polyamine analogue, on the in vitro and in vivo models of cerebral ischemic damage. The results revealed that pretreatment with QMA could attenuate Glu, putrescine (Put) and oxygen-glucose deprivation (OGD)-induced cell death, lipid peroxidation as well as the elevation of reactive oxygen species (ROS) and intracellular [Ca(2+)](i) in pheochromocytoma (PC12) cells and in rat primary cortical neurons. The results also demonstrated that QMA could inhibit NMDA-mediated intracellular [Ca(2+)](i) accumulation in rat primary cortical neurons and reduce brain infarct volume in middle cerebral artery occlusion (MCAO) rats. The present report suggested that polyamines played a crucial role in the pathological processes of cerebral ischemic damage and that QMA or other novel polyamine analogues could be promising therapeutic candidates for stroke by virtue of their anti-hypoxia and antioxidation property.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475004, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Man
authors.initials: M
authors.lastname: Liu
authors.forename: Chao-Jie
authors.initials: CJ
authors.lastname: Wang
authors.forename: Bian-Sheng
authors.initials: BS
authors.lastname: Ji
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology; D004396:Coloring Agents; D005947:Glucose / Q000172:deficiency; D005979:Glutathione Peroxidase / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D016716:PC12 Cells; D011073:Polyamines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004396:Coloring Agents; C579386:N(1)-(quinolin-2-ylmethyl)butane-1,4-diamine; D018696:Neuroprotective Agents; D011073:Polyamines; D011804:Quinolines; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; C022616:thiazolyl blue; D005947:Glucose; D002118:Calcium