Melatonin treatment further improves adipose‐derived mesenchymal stem cell therapy for acute interstitial cystitis in rat |
| |
| Authors: | Chih‐Hung Chen Pei‐Hsun Sung Fan‐Yen Lee Tzu‐Hsien Tsai Chia‐Lo Chang Hong‐Hwa Chen Cheuk‐Kwan Sun Steve Leu Hsueh‐Wen Chang Hon‐Kan Yip |
| |
| Institution: | 1. Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;2. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;3. Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;4. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;5. Department of Emergency Medicine, E‐DA Hospital, I‐Shou University, , Kaohsiung, Taiwan;6. Department of Biological Sciences, National Sun Yat‐Sen University, , Kaohsiung, Taiwan;7. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;8. Institute of Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan |
| |
| Abstract: | This study tests the hypothesis that combined melatonin and adipose‐derived mesenchymal stem cell (ADMSC, 1.2 × 106 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. |
| |
| Keywords: | acute interstitial cystitis adipose‐derived mesenchymal stem cells cyclophosphamide inflammation oxidative stress melatonin |
|
|
