Biomolecules & Therapeutics

  • 제23권2호
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  • Pages.180-188
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  • 2015
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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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)
  • 투고 : 2014.11.13
  • 심사 : 2015.01.12
  • 발행 : 2015.03.01
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초록

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.

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