Calzi F, Bellasio R, Guiso G, Caccia S, Tacconi M T
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Eur J Pharmacol. 1997 Nov 5;338(2):185-90. doi: 10.1016/s0014-2999(97)81947-4.
We studied the effect of piribedil (1-3,4-methylendioxybenzyl-4-(2-pyrimidyl) piperazine) and its catechol metabolite, S584 (1-(3,4-dihydroxybenzyl-4-(2-pyrimidinyl)-piperazine), on rat brain lipid peroxidation (a) in vitro in rat synaptosomes and cortical slices after induction of an oxidative stress and (b) in vivo in mouse brain after short-term exposure (two and three 4-h cycles) to O2/CO2 (95%:5%). The metabolite (10[-4]-10[-5] M), but not piribedil, prevented Fe3+-stimulated lipid peroxidation in rat synaptosomes and in rat cortical slices incubated with high oxygen concentrations. Piribedil (7.5 and 30 mg/kg, orally), counteracted the increase in thiobarbituric reactive substances in the brain of mice only when these were exposed to two or three cycles of a high oxygen concentration. S584 (30 mg/kg, orally) reduced thiobarbituric acid reactive substances in brain in mice exposed either to air (control) or to three cycles of a high oxygen concentration. These results suggest that piribedil has an antiperoxidative effect in brain, which may be partly related to the in vivo formation of the catechol metabolite, S584.
我们研究了吡贝地尔（1 - 3,4 - 亚甲基二氧基苄基 - 4 -（2 - 嘧啶基）哌嗪）及其儿茶酚代谢物S584（1 -（3,4 - 二羟基苄基 - 4 -（2 - 嘧啶基） - 哌嗪）对大鼠脑脂质过氧化的影响：（a）在体外，对诱导氧化应激后的大鼠突触体和皮质切片进行研究；（b）在体内，对小鼠脑进行研究，小鼠短期暴露（两个和三个4小时周期）于O2/CO2（95%:5%）环境。代谢物（10[-4]-10[-5] M）而非吡贝地尔，可预防高氧浓度孵育的大鼠突触体和大鼠皮质切片中Fe3+刺激的脂质过氧化。仅当小鼠暴露于两个或三个高氧浓度周期时，吡贝地尔（7.5和30 mg/kg，口服）可抵消小鼠脑中硫代巴比妥酸反应性物质的增加。S584（30 mg/kg，口服）可降低暴露于空气（对照）或三个高氧浓度周期的小鼠脑中硫代巴比妥酸反应性物质。这些结果表明，吡贝地尔在脑中具有抗过氧化作用，这可能部分与儿茶酚代谢物S584的体内形成有关。
