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http://dx.doi.org/10.4062/biomolther.2014.126

Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways  

Kim, Sung Hwan (College of Veterinary Medicine, Chonnam National University)
Lee, In Chul (College of Veterinary Medicine, Chonnam National University)
Ko, Je Won (College of Veterinary Medicine, Chonnam National University)
Moon, Changjong (College of Veterinary Medicine, Chonnam National University)
Kim, Sung Ho (College of Veterinary Medicine, Chonnam National University)
Shin, In Sik (College of Veterinary Medicine, Chonnam National University)
Seo, Young Won (Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology)
Kim, Hyoung Chin (Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology)
Kim, Jong Choon (College of Veterinary Medicine, Chonnam National University)
Publication Information
Biomolecules & Therapeutics / v.23, no.2, 2015 , pp. 180-188 More about this Journal
Abstract
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 mitogen-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 CP-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 CP-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.
Keywords
Cyclophosphamide; Hemorrhagic cystitis; Diallyl disulfide; Oxidative damage; MAPKs; NF-${\kappa}B$;
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