Onur Rahmi, Tasdemir Cemal, Seckin Dilara, Ilhan Necip, Kutlu Selim, Akpolat Nusret
Department of Urology, Biochemistry, Physiology, and Pathology, Firat University Faculty of Medicine, Elazig, Turkey.
Urology. 2008 Aug;72(2):439-43. doi: 10.1016/j.urology.2008.02.053. Epub 2008 May 2.
To investigate the effects of terazosin and melatonin on isolated rabbit bladder strips after partial bladder outlet obstruction and determine responses to agonist-induced contractility and changes in oxidant-antioxidant system.
We created partial bladder outlet obstruction in 5 groups of rabbits, each containing 8. Rabbits with sham operation (group 1) received no drug treatment. Similarly, animals in group 2 underwent partial bladder outlet obstruction and received no drug treatment. Rabbits in groups 3 were administered 5 mg/day oral terazosin, and rabbits in group 4 received 10 mg/kg/day melatonin intraperitoneally. Animals in group 5 received both terazosin and melatonin. We removed their bladders and performed histopathological and biochemical measurements. We assessed tissue malondialdehyde and antioxidant enzyme activity levels and recorded in vitro contractility response to KCl in isolated organ baths.
The thickness of muscularis propria was significantly increased in group 2 compared with all other groups. KCl-evoked contractions after partial outlet obstruction were significantly impaired in group 3 and 4 animals receiving terazosin and melatonin, respectively. However, combined use of melatonin and terazosin in group 5 showed contractility responses similar to sham-operated animals (P <0.05). Melatonin administration to groups 4 and 5 showed decreased levels of lipid peroxidation. Similarly, animals receiving melatonin and melatonin plus terazosin showed statistically significant increase in antioxidant enzyme activities.
In the present study, we showed that oxidative stress induced by partial bladder outlet obstruction can be successfully antagonized by the potent antioxidant melatonin, and its combined use with an alpha-antagonist such as terazosin may restore in vitro contractility.
研究特拉唑嗪和褪黑素对部分膀胱出口梗阻后离体兔膀胱条的影响,并确定对激动剂诱导的收缩性以及氧化-抗氧化系统变化的反应。
我们将5组兔子造成部分膀胱出口梗阻,每组8只。假手术组(第1组)兔子未接受药物治疗。同样,第2组动物进行了部分膀胱出口梗阻且未接受药物治疗。第3组兔子口服5毫克/天的特拉唑嗪,第4组兔子腹腔注射10毫克/千克/天的褪黑素。第5组动物同时接受特拉唑嗪和褪黑素。我们取出它们的膀胱并进行组织病理学和生化测量。我们评估了组织丙二醛和抗氧化酶活性水平,并记录了离体器官浴中对氯化钾的体外收缩反应。
与所有其他组相比,第2组固有肌层厚度显著增加。分别接受特拉唑嗪和褪黑素的第3组和第4组动物在部分出口梗阻后氯化钾诱发的收缩明显受损。然而,第5组中褪黑素和特拉唑嗪联合使用显示出与假手术动物相似的收缩反应(P<0.05)。第4组和第5组给予褪黑素后脂质过氧化水平降低。同样,接受褪黑素以及褪黑素加特拉唑嗪的动物抗氧化酶活性有统计学意义的增加。
在本研究中,我们表明部分膀胱出口梗阻诱导的氧化应激可被强效抗氧化剂褪黑素成功拮抗,并且其与α拮抗剂如特拉唑嗪联合使用可能恢复体外收缩性。