Sener Göksel, Sehirli Ozer, Toklu Hale, Ercan Feriha, Alican Inci
Marmara University, Faculty of Pharmacy, Department of Pharmacology, Haydarpaşa, 34668, Istanbul, Turkey.
J Pharm Pharmacol. 2007 Jun;59(6):837-42. doi: 10.1211/jpp.59.6.0009.
The present study aimed to investigate the possible beneficial effects of the cysteinyl leukotriene-1 receptor antagonist montelukast on contractility and oxidant damage after ischaemia/reperfusion (I/R) of rat urinary bladder. The abdominal aorta of Sprague-Dawley rats was occluded to induce I/R. Montelukast (10 mg kg(-1)) or saline was administered intraperitoneally before I/R. In the sham-operated group, the abdominal aorta was left intact and the animals were treated with montelukast or saline. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for biochemical assays. In the I/R group, the isometric contractile responses of the bladder strips to carbachol (10(-8)-10(-4) M) were lower than those of the control group and were reversed by treatment with montelukast. Lipid peroxidation and myeloperoxidase activity of the bladder tissues in the I/R group were greater than in the sham-operated group. Montelukast treatment in the I/R group decreased these parameters compared with I/R alone. Similarly, the significant decrease in tissue glutathione level in the I/R group compared with controls was also prevented by montelukast. Treatment with montelukast almost completely reversed the low contractile responses of rat urinary bladder to carbachol and prevented oxidative tissue damage following I/R.
本研究旨在探讨半胱氨酰白三烯-1受体拮抗剂孟鲁司特对大鼠膀胱缺血/再灌注(I/R)后收缩性和氧化损伤的可能有益作用。阻断Sprague-Dawley大鼠的腹主动脉以诱导I/R。在I/R前腹腔注射孟鲁司特(10 mg·kg⁻¹)或生理盐水。在假手术组中,腹主动脉保持完整,动物接受孟鲁司特或生理盐水治疗。断头后,取出膀胱,将组织用于功能研究或储存用于生化分析。在I/R组中,膀胱条对卡巴胆碱(10⁻⁸ - 10⁻⁴ M)的等长收缩反应低于对照组,且孟鲁司特治疗可使其逆转。I/R组膀胱组织的脂质过氧化和髓过氧化物酶活性高于假手术组。与单独I/R相比,I/R组孟鲁司特治疗降低了这些参数。同样,与对照组相比,I/R组组织谷胱甘肽水平的显著降低也被孟鲁司特阻止。孟鲁司特治疗几乎完全逆转了大鼠膀胱对卡巴胆碱的低收缩反应,并预防了I/R后的氧化组织损伤。