美替洛尔减轻大鼠脑内脂质过氧化：与其他抗青光眼药物的比较研究。

Metipranolol attenuates lipid peroxidation in rat brain: a comparative study with other antiglaucoma drugs.

作者信息

Melena José, Osborne Neville N

机构信息

Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford, OX2 6AW, UK.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2003 Oct;241(10):827-33. doi: 10.1007/s00417-003-0726-5. Epub 2003 Jul 29.

DOI:10.1007/s00417-003-0726-5

PMID:12898280

Abstract

BACKGROUND

Free radical production seems to be involved in the pathogenesis of a number of ocular diseases. Certain beta-adrenoceptor antagonists display antioxidant properties, but these have not been ascribed to any of the presently used ophthalmic beta-adrenoceptor antagonists. Therefore, we examined the influence of ophthalmic beta-adrenoceptor antagonists and other antiglaucoma drugs on stimulated lipid peroxidation in rat brain homogenates.

METHODS

Lipid peroxidation in rat brain homogenates was stimulated by iron/ascorbate or sodium nitroprusside. Lipid peroxidation was assessed by the formation of thiobarbituric acid reactive species (TBARS).

RESULTS

Of the antiglaucoma drugs tested (brimonidine, carteolol, dorzolamide, latanoprost, levobetaxolol, levobunolol, metipranolol, pilocarpine, timolol, travoprost and unoprostone), only metipranolol and its active metabolite, desacetylmetipranolol, were found to significantly reduce iron/ascorbate-induced lipid peroxidation in rat brain homogenates with IC50 values of 6.9 and 1.1 microM, respectively. Metipranolol and desacetylmetipranolol also concentration-dependently inhibited sodium nitroprusside-stimulated lipid peroxidation in rat brain homogenates, displaying IC50 values of 25.1 and 2.6 microM, respectively.

CONCLUSION

These data indicate that metipranolol and desacetylmetipranolol exhibit remarkable antioxidant properties, with an effect not dissimilar from the reference antioxidant trolox.

摘要

背景

自由基生成似乎参与了多种眼部疾病的发病机制。某些β-肾上腺素能受体拮抗剂具有抗氧化特性，但目前使用的眼科β-肾上腺素能受体拮抗剂均未被认为具有此特性。因此，我们研究了眼科β-肾上腺素能受体拮抗剂及其他抗青光眼药物对大鼠脑匀浆中刺激诱导的脂质过氧化的影响。

方法

用铁/抗坏血酸或硝普钠刺激大鼠脑匀浆中的脂质过氧化。通过硫代巴比妥酸反应性物质（TBARS）的形成来评估脂质过氧化。

结果

在所测试的抗青光眼药物（溴莫尼定、卡替洛尔、多佐胺、拉坦前列素、左布诺洛尔、左噻吗洛尔、美替洛尔、毛果芸香碱、噻吗洛尔、曲伏前列素和乌诺前列酮）中，仅发现美替洛尔及其活性代谢物去乙酰美替洛尔能显著降低铁/抗坏血酸诱导的大鼠脑匀浆脂质过氧化，IC50值分别为6.9和1.1微摩尔/升。美替洛尔和去乙酰美替洛尔也能浓度依赖性地抑制硝普钠刺激的大鼠脑匀浆脂质过氧化，IC50值分别为25.1和2.6微摩尔/升。