al-Gharably N M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Res Commun Mol Pathol Pharmacol. 1996 Dec;94(3):289-303.
Probucol [(4,4'-(-(isopropylidenedithio) bis (2,6-di-t-butylphenol)], a hypolipidemic drug, was evaluated for its effects on the clastogenic activity of ADM in Swiss albino mice. Male mice were treated i.p. with different doses (25, 50 and 100 mg/kg, body weight/day) of probucol for 7 days. Some of the mice in each dose group of probucol and those in the positive control group were injected i.p. with Adriamycin (ADM, 8 mg/kg, body weight) and killed after 24 hr. Femoral cells of mice were collected and studied for the frequency of micronuclei and the ratio of polychromatic erythrocytes to Normochromatic erythrocytes. Furthermore, proteins, DNA, RNA, Malondialdehyde (MDA) and non-protein sulfhydryl (NP-SH) levels were determined in the hepatic cells. Probucol treatment failed to induce any significant clastogenic, cytotoxic and biochemical changes. However, pre-treatment with probucol was found to reduce the ADM-induced micronuclei without any alteration in its cytotoxicity. The DNA, RNA, proteins and NP-SH levels in the hepatic cells of these animals were increased and the MDA concentrations were reduced. The inhibition of ADM-induced clastogenicity by probucol may be attributed to its lipids lowering, iron chelating, free radical scavenging and topoisomerase-II-depleting action.
普罗布考[（4,4'-（亚异丙基二硫代）双（2,6-二叔丁基苯酚）]，一种降血脂药物，在瑞士白化小鼠中评估了其对阿霉素（ADM）致断裂活性的影响。雄性小鼠腹腔注射不同剂量（25、50和100毫克/千克体重/天）的普罗布考，持续7天。普罗布考各剂量组中的一些小鼠以及阳性对照组的小鼠腹腔注射阿霉素（ADM，8毫克/千克体重），24小时后处死。收集小鼠的股骨细胞，研究微核频率以及多染性红细胞与正染性红细胞的比例。此外，还测定了肝细胞中的蛋白质、DNA、RNA、丙二醛（MDA）和非蛋白巯基（NP-SH）水平。普罗布考处理未诱导任何显著的致断裂、细胞毒性和生化变化。然而，发现普罗布考预处理可减少ADM诱导的微核，而其细胞毒性无任何改变。这些动物肝细胞中的DNA、RNA、蛋白质和NP-SH水平升高，MDA浓度降低。普罗布考对ADM诱导的致断裂性的抑制作用可能归因于其降血脂、铁螯合、自由基清除和拓扑异构酶-II消耗作用。
