期刊
FREE RADICAL RESEARCH
卷 43, 期 4, 页码 329-339出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715760902736283
关键词
MnTE-2-PyP5+(AEOL10113); MnTnOct-2-PyP5+; MnTDE-2-ImP5+(AEOL10150); neuronal; glial cell culture; organotypic hippocampal slices (OHS); oxygen and glucose deprivation (OGD)
资金
- NIH [T32 GM08600-09, RO1 GM067139-03]
- National Institutes of Health [IR21-ESO/ 3682]
- National Institutes for Allergy and Infectious Diseases [U19AI067798]
- NIH/ NCI Duke Comprehensive Cancer Center Core [5-P30-CA14236-29]
- NATIONAL CANCER INSTITUTE [P30CA014236] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI067798] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM067139, T32GM008600] Funding Source: NIH RePORTER
In vivo investigations have confirmed the beneficial effects of hydrophilic, cationic Mn(III) porphyrin-based catalytic antioxidants in different models of oxidative stress. Using a cell culture model of rat mixed neuronal/glial cells, this study investigated the effect of MnTnOct-2-PyP5+ on oxygen and glucose deprivation (OGD)-induced cell death as compared to the effects of widely studied hydrophilic analogues MnTE-2-PyP5+ and MnTDE-2-ImP5+ and a standard compound, dizocilpine (MK-801). It was hypothesized that the octylpyridylporphyrin, MnTnOct-2-PyP5+, a lipophilic but equally potent antioxidant as the other two porphyrins, would be more efficacious in reducing OGD-induced cell death due to its higher bioavailability. Cell death was evaluated at 24 h using lactate dehydrogenase (LDH) release and propidium iodide staining. At concentrations from 3-100 m, all three porphyrins reduced cell death as compared to cultures exposed to OGD alone, the effects depending upon the concentrations and type of treatment. To assess the effect of lipophilicity the additional experiments were performed using submicromolar concentrations of MnTnOct-2-PyP5+ in an organotypic hippocampal slice model of OGD with propidium iodide and Sytox staining. When compared to oxygen and glucose deprivation alone, concentrations of MnTnOct-2-PyP5+ as low as 0.01 m significantly (p0.001; power 1.0) reduced neuronal cells similar to control. This is the first in vitro study on the mammalian cells which indicates that MnTnOct-2-PyP5+ is up to 3000-fold more efficacious than equally potent hydrophilic analogues, due entirely to its increased bioavailability. Such remarkable increase in efficacy parallels 5.7-orders of magnitude increase in lipophilicity of MnTnOct-2-PyP5+ (log P=-0.77) when compared to MnTE-2-PyP5+ (log Pow=-6.43), Pow being partition coefficient between n-octanol and water.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据