Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey.
Deparment of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey.
Int Urol Nephrol. 2019 May;51(5):803-810. doi: 10.1007/s11255-019-02128-y. Epub 2019 Mar 20.
Hemorrhagic cystitis (HC) is defined as any types of acute or chronic inflammation of urinary bladder with several reasons. One of the most common causes of HC is cyclophosphamide (CYP), an effective antineoplastic agent, due to its urotoxic potential. Ambroxol (AMB) is a mucoactive drug that has been used for numerous respiratory diseases. Besides its mucolytic activity, AMB is a potent antioxidant and antiinflammatory agent that is becoming more attractive for the treatment of several oxidative/inflammatory disorders. The aim of this study was to evaluate the uroprotective potential of AMB in CYP-induced HC.
Male Balb/c mice were pretreated with AMB (30, 70, and 100 mg/kg) once a day for 3 consecutive days before HC induction with CYP (300 mg/kg). Mesna (30 mg/kg;i.p.), only drug in the management of CYP-induced HC, was administered 20 min before; 4 and 8 h after cystitis induction. The urinary bladders were harvested and evaluated in functional, biochemical, and histological studies.
CYP-induced HC markedly reduced acetylcholine (ACh)-induced contractions in detrusor strips and AMB at 100 mg/kg caused a significant increase in the responsiveness to ACh. Pretreatment with AMB prevented the elevation of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) level, reduction of total glutathione (GSH) that induced by CYP. However, treatment with AMB did not improve the bladder weight and some histological parameters.
These results suggest that AMB pretreatment could improve CYP-induced HC via antioxidant and antiinflammatory activities.
血尿症（HC）被定义为任何类型的急性或慢性膀胱炎症，其原因有多种。HC 的最常见原因之一是环磷酰胺（CYP），这是一种有效的抗肿瘤药物，由于其潜在的尿毒性。氨溴索（AMB）是一种黏液活性药物，已被用于多种呼吸系统疾病。除了其黏液溶解活性外，AMB 还是一种有效的抗氧化剂和抗炎剂，对于治疗多种氧化/炎症性疾病变得越来越有吸引力。本研究旨在评估 AMB 在 CYP 诱导的 HC 中的尿保护潜力。
雄性 Balb/c 小鼠在 CYP（300mg/kg）诱导 HC 前，连续 3 天每天接受 AMB（30、70 和 100mg/kg）预处理一次。美司钠（30mg/kg；腹腔注射），仅用于 CYP 诱导的 HC 管理的药物，在诱导膀胱炎前 20 分钟；4 和 8 小时后给予。收集膀胱并进行功能、生化和组织学研究。
CYP 诱导的 HC 明显降低了逼尿肌条中乙酰胆碱（ACh）诱导的收缩，AMB 以 100mg/kg 的剂量可显著增加对 ACh 的反应性。AMB 预处理可防止 CYP 诱导的丙二醛（MDA）和肿瘤坏死因子-α（TNF-α）水平升高，总谷胱甘肽（GSH）减少。然而，AMB 治疗并未改善膀胱重量和一些组织学参数。
这些结果表明，AMB 预处理可通过抗氧化和抗炎活性改善 CYP 诱导的 HC。
