title: Protective effects of lipoic acid and mesna on cyclophosphamide-induced haemorrhagic cystitis in mice.
abstract: 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.
authors: Key Laboratory of Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, China.
authors: Jianbo
authors: J
authors: Song
authors: Lichao
authors: L
authors: Liu
authors: Lingrui
authors: L
authors: Li
authors: Jing
authors: J
authors: Liu
authors: Erqun
authors: E
authors: Song
authors: Yang
authors: Y
authors: Song
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004357:Drug Synergism; D006417:Hematuria / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D020935:MAP Kinase Signaling System; D015080:Mesna / Q000627:therapeutic use*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D003520:Cyclophosphamide; D015080:Mesna; D001205:Ascorbic Acid
keywords: cyclophosphamide; haemorrhagic cystitis; lipoic acid; mesna; oxidative stress