Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-kappaB Pathways.
10.4062/biomolther.2014.126
- Author:
Sung Hwan KIM
1
;
In Chul LEE
;
Je Won KO
;
Changjong MOON
;
Sung Ho KIM
;
In Sik SHIN
;
Young Won SEO
;
Hyoung Chin KIM
;
Jong Choon KIM
Author Information
1. College of Veterinary Medicine, Chonnam National University, Gwangju 500-757. toxkim@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
Cyclophosphamide;
Hemorrhagic cystitis;
Diallyl disulfide;
Oxidative damage;
MAPKs;
NF-kappaB
- MeSH:
Animals;
Cyclooxygenase 2;
Cyclophosphamide;
Cystitis*;
Cytokines;
DNA Damage;
Glutathione;
Glutathione Reductase;
Inflammation;
Malondialdehyde;
Mitogen-Activated Protein Kinases;
NF-kappa B*;
Nitric Oxide Synthase Type II;
Oxidative Stress;
Phosphotransferases;
Rats*;
Transcription Factors;
Tumor Necrosis Factor-alpha;
Urinary Bladder
- From:Biomolecules & Therapeutics
2015;23(2):180-188
- CountryRepublic of Korea
- Language:English
-
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-kappaB), 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-kappaB, 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-kappaB, 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-kappaB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.
