title: Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat.
abstract: This study tests the hypothesis that combined melatonin and adipose-derived mesenchymal stem cell (ADMSC, 1.2 × 10(6) given intravenously) treatment offer superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC + melatonin +ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at 30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine volume, urine albumin level, and severity of hematuria were highest in AIC rats and lowest in the controls; likewise urine volume was higher in AIC + melatonin rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases, P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells and protein expression of IL-6, IL-12, RANTES, TNF-α, NF-κB, MMP-9, iNOS (i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4) in the bladder tissue exhibited an identical pattern compared with that of hematuria among the five groups (all P < 0.0001). The integrity of epithelial layer and area of collagen deposition displayed an opposite pattern compared to that of hematuria among all groups (P < 0.0001). The cellular expressions of antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of melatonin and ADMSC was superior to either alone in protecting against CYP-induced AIC.
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Chiang
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.forename: Hong-Hwa
authors.initials: HH
authors.lastname: Chen
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018856:Cystitis, Interstitial / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D016207:Cytokines; D008550:Melatonin
keywords: acute interstitial cystitis; adipose-derived mesenchymal stem cells; cyclophosphamide; inflammation; melatonin; oxidative stress