Albany College of Pharmacy and Health Sciences, 106 New Scotland Ave, Albany, NY 12208, USA.
Int Urol Nephrol. 2011 Mar;43(1):91-7. doi: 10.1007/s11255-010-9771-2. Epub 2010 Jun 8.
Partial bladder outlet obstruction (PBOO) in rabbits causes free radical production through ischemia and reperfusion within the bladder smooth muscle and mucosa. We had previously shown that pretreatment of rabbits with a combination of α-lipoic acid (αLA) and coenzyme Q10 (CoQ) protected the bladder from contractile and metabolic dysfunctions mediated by PBOO. In this study, we examined the ability of pretreatment with αLA and CoQ combination in rabbits to protect the bladder from contractile damage mediated by either hydrogen peroxide (H(2)O(2)) or in vitro ischemia-reperfusion (I/R) which represents two in vitro models of oxidative damage.
Eight adult male New Zealand white rabbits were pretreated with CoQ and αLA orally for four weeks. Eight adult male control rabbits were given vehicle. Eight full-thickness bladder strips were isolated from each of 4 treated and 4 control rabbit bladders, and a dose-response curve to H(2)O(2) (0.1-0.8%) was generated. Similarly, isolated strips of bladder from the remaining 4 control and 4 treated rabbits were subjected to 1 h of ischemia (no oxygen without glucose) followed by 2 h of incubation in oxygenated buffer with glucose. The effects on the contractile responses to field stimulation (FS) at 2, 8, and 32 Hz, carbachol, and potassium chloride (KCl) were determined.
H(2)O(2) reduced the contractile responses to KCl and carbachol to a significantly greater degree than to FS, whereas I/R reduced the contractile responses to FS to a significantly greater degree than to KCl and carbachol. Pretreatment of the rabbits with the combination of CoQ and αLA significantly protected the bladder from the damaging effects of I/R, but had virtually no effect on the damaging effects of H(2)O(2).
Although both H(2)O(2) and I/R are in vitro models of oxidative free radical damage to bladder smooth muscle, they have significantly different methods of action and different sensitivities to antioxidants.
兔部分膀胱出口梗阻（PBOO）导致膀胱平滑肌和黏膜缺血再灌注时自由基的产生。我们之前的研究表明，预先用α-硫辛酸（αLA）和辅酶 Q10（CoQ）联合处理兔子可以防止 PBOO 介导的膀胱收缩和代谢功能障碍。在这项研究中，我们检测了αLA 和 CoQ 联合预处理对兔子膀胱的保护作用，以防止两种体外氧化损伤模型，即过氧化氢（H2O2）或体外缺血再灌注（I/R）引起的收缩损伤。
8 只成年雄性新西兰白兔经口给予 CoQ 和 αLA 预处理 4 周。8 只成年雄性对照兔给予载体。从 4 只治疗兔和 4 只对照兔的膀胱中分离 8 个全层膀胱条，生成 H2O2（0.1%-0.8%）的剂量反应曲线。同样，来自剩余 4 只对照兔和 4 只治疗兔的膀胱条在缺氧（无葡萄糖）1 小时后进行缺血，然后在含氧含葡萄糖的缓冲液中孵育 2 小时。确定对场刺激（FS）在 2、8 和 32 Hz、卡巴胆碱和氯化钾（KCl）时的收缩反应的影响。
H2O2 降低了对 KCl 和卡巴胆碱的收缩反应，比 FS 降低的程度显著更大，而 I/R 降低了对 FS 的收缩反应，比 KCl 和卡巴胆碱降低的程度显著更大。用 CoQ 和 αLA 联合处理兔子可显著保护膀胱免受 I/R 的损害作用，但对 H2O2 的损害作用几乎没有影响。
虽然 H2O2 和 I/R 都是膀胱平滑肌氧化自由基损伤的体外模型，但它们的作用方式有很大的不同，对抗氧化剂的敏感性也不同。
