title: Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways.
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-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), 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-κB, COX-2, iNOS, TNF-α, 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-κB, COX-2, iNOS, TNF-α, 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-κB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 ; Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeonbuk 580-185.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: In Chul
authors.initials: IC
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Je Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 ; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883.
authors.forename: In Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Young Won
authors.initials: YW
authors.lastname: Seo
authors.affiliation: Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Hyoung Chin
authors.initials: HC
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Jong Choon
authors.initials: JC
authors.lastname: Kim
keywords: Cyclophosphamide; Diallyl disulfide; Hemorrhagic cystitis; MAPKs; NF-κB; Oxidative damage