Song Jianbo, Liu Lichao, Li Lingrui, Liu Jing, Song Erqun, Song Yang
Key Laboratory of Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, China.
Cell Biochem Funct. 2014 Mar;32(2):125-32. doi: 10.1002/cbf.2978. Epub 2013 May 5.
The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.
研究了硫辛酸（LA）/维生素C（VC）和美司钠对预防环磷酰胺（CYP）诱导的出血性膀胱炎（HC）的保护作用。将瑞士小鼠随机分为五组。通过单次注射CYP（150 mg kg⁻¹体重）诱导HC。第一组全程注射生理盐水（共四次）作为对照组。第二组接受CYP和三次等量的生理盐水。第三组接受CYP和三次美司钠注射，而第四组（或第五组）接受CYP、美司钠加两次VC（或LA）注射。所有注射均通过腹腔内进行。膀胱炎诱导24小时后，收集所有实验组的膀胱。组织学特征显示，注射CYP导致严重的HC。CYP组中活性氧（ROS）和硫代巴比妥酸反应性物质的水平升高。CYP组中超氧化物歧化酶、过氧化氢酶、谷胱甘肽S-转移酶和谷胱甘肽过氧化物酶等抗氧化酶的活性分别受到显著抑制。此外，c-jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）的激活可能参与CYP诱导的HC机制，但细胞外信号调节激酶（ERK）不参与。第五组中p38磷酸化的显著抑制表明LA和美司钠可能具有协同有益作用。在第三至五组中，HC和氧化应激的所有参数均受到显著抑制。综上所述，我们发现这些结果表明ROS在CYP诱导的HC中起重要作用，并且LA/VC与美司钠联合给药可能对CYP诱导的膀胱HC具有治疗潜力。
