期刊
BIOMOLECULES & THERAPEUTICS
卷 23, 期 2, 页码 180-188出版社
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2014.126
关键词
Cyclophosphamide; Hemorrhagic cystitis; Diallyl disulfide; Oxidative damage; MAPKs; NF-kappa B
资金
- Basic Science Research Program through National Research Foundation of Korea - Ministry of Education, Science and Technology [NRF-2013R1A1A2010835]
- KRIBB Research Initiative program
- Animal Medical Institute of Chonnam National University
This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-kappa B), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of nnitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-kappa B, COX-2, iNOS, TNF-alpha, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CF-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-kappa B, COX-2, iNOS, TNF-alpha, p-JNK, and p-ERK. These results indicate that DADS prevents CF-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-kappa B and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据