Kitani K, Kanai S, Ivy G O, Carrillo M C
National Institute for Longevity Sciences, Aichi, Japan.
Mech Ageing Dev. 1999 Nov;111(2-3):211-21. doi: 10.1016/s0047-6374(99)00065-2.
Limited information is available on the upregulation of endogenous antioxidant enzymes by means of administering various pharmaceuticals and/or chemicals. It has been reported that ursodeoxycholic acid (UDCA), a bile acid originally identified from black bear bile (a Chinese medicine, Yutan) increased glutathione S-transferase (GST) activities in mouse livers, resulting in a decrease in systemic lethal toxicity of orally challenged 1-2-dichloro-4-nitrobenzene (DCNB). Also, ursolic acid found in herbal medicines (e.g. leaves of loquat) was reported to increase catalase (CAT) activities in mouse liver. Interestingly, the chemical structures of these two compounds are surprisingly similar to each other, despite the difference in their original sources. These results suggest that in the future, more and more compounds will be found to have effects on increasing endogenous antioxidant enzyme activities. Deprenyl is a monoamine oxidase B inhibitor but also possesses many other different pharmacological activities. Among these various pharmacological effects of deprenyl, a possible causal relationship between two effects of deprenyl, namely the prolongation of the survival of animals and upregulation of antioxidant enzymes in selective brain regions, has been postulated by the authors. In at least four different animal species (rats, mice, hamsters and dogs), a significant prolongation of survival by chronic administration of the drug has been reported by different groups including that of the authors. This group has reported that repeated administration of the drug for 2-3 weeks can significantly increase activities of both types of superoxide dismutase (SODs) (Cu, Zn-, and Mn-SODs) as well as of CAT selectively in brain dopaminergic regions. Both effects are dose dependent but excessive dosages become less effective and even cause an adverse effect (i.e. a decrease in enzyme activities and shortening of life span). The parallelism of the dose-effect relationship between the two phenomena suggests that modification of SOD and CAT levels is one possible mechanism for deprenyl's ability to prolong the life span of animals.
关于通过施用各种药物和/或化学物质来上调内源性抗氧化酶的信息有限。据报道，熊去氧胆酸（UDCA），一种最初从黑熊胆汁（一种中药，鱼胆）中鉴定出的胆汁酸，可增加小鼠肝脏中谷胱甘肽S-转移酶（GST）的活性，从而降低口服1-2-二氯-4-硝基苯（DCNB）后的全身致死毒性。此外，据报道，草药（如枇杷叶）中发现的熊果酸可增加小鼠肝脏中的过氧化氢酶（CAT）活性。有趣的是，尽管这两种化合物的原始来源不同，但它们的化学结构却惊人地相似。这些结果表明，未来会发现越来越多的化合物具有增加内源性抗氧化酶活性的作用。司来吉兰是一种单胺氧化酶B抑制剂，但也具有许多其他不同的药理活性。在司来吉兰的这些各种药理作用中，作者推测了司来吉兰的两种作用之间可能存在因果关系，即动物存活时间的延长和选择性脑区抗氧化酶的上调。在至少四种不同的动物物种（大鼠、小鼠、仓鼠和狗）中，包括作者所在的研究小组在内的不同研究团队都报告称，长期施用该药物可显著延长动物的存活时间。该研究小组报告称，重复给药2-3周可显著增加两种超氧化物歧化酶（SOD，即铜锌超氧化物歧化酶和锰超氧化物歧化酶）以及脑多巴胺能区域中CAT的活性。这两种作用均呈剂量依赖性，但过量用药效果会减弱，甚至会产生不良反应（即酶活性降低和寿命缩短）。这两种现象之间剂量效应关系的平行性表明，改变SOD和CAT水平可能是司来吉兰延长动物寿命的一种机制。
