Intravesical Instillation of Hyaluronic Acid With Epidermal Growth Factor for Restoring Urothelial Denudation and Alleviating Oxidative Stress in Lipopolysaccharide-Induced Interstitial Cystitis of Rats
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. Methods: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. Results: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. Conclusions: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.
Abstract
Purpose: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. Methods: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. Results: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. Conclusions: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.
참고문헌 (26)
- Clemens JQ, "Diagnosis and treatment of interstitial cystitis", bladder pain syndrome, 2022, pp.208, 34~42
- Xu Y, "Human umbilical cord mesenchymal stem cell therapy mitigates interstitial cystitis by inhibiting mast cells", Med Sci Monit, 27, pp.e930001~ (2021)
- Liu HT, "Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis", bladder pain syndrome, 2012, pp.80, 225~
- Wyndaele M, "Beyond the urothelium : Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023", Neurourol Urodyn (2023)[DOI]
- Jasmin L, "Experimental neurogenic cystitis", Adv Exp Med Biol, 539(Pt A), pp.319~335 (2003)
- van de Merwe JP, "Interstitial cystitis and systemic autoimmune diseases", Nat Clin Pract Urol, 4, pp.484~491 (2007)
- Lai MC, "Intravesical hyaluronic acid for interstitial cystitis", painful bladder syndrome : a comparative randomized assessment of different regimens, 2013, pp.20, 203~207
- Ravery V, "Evaluation of epidermal growth factor receptor, transforming growth factor alpha, epidermal growth factor and c-erbB2 in the progression of invasive bladder cancer", Urol Res, 25, pp.9~17 (1997)
- Lau JL, "Epidermal growth factor in the normal and neoplastic kidney and bladder", J Urol, 139, pp.170~175 (1988)
- Messing EM, "Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma", Cancer Res, 50, pp.2530~2537 (1990)
- Freeman MR, "Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder", J Clin Invest, 99, pp.1028~1036 (1997)
- Rocourt DV, "Heparin-binding EGF-like growth factor decreases inflammatory cytokine expression after intestinal ischemia", reperfusion injury, 2007, pp.139, 269~273
- Kim S, "Role of heparin-binding epidermal growth factor-like growth factor in oxidative stressassociated metabolic diseases", Metab Syndr Relat Disord, 18, pp.186~196 (2020)
- Erickson DR, "A comparison of multiple urine markers for interstitial cystitis", J Urol, 167, pp.2461~2469 (2002)
- Keay S, "Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls", J Urol, 158, pp.1983~1988 (1997)
- Morales A, "Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis", Urology, 49(5A Suppl), pp.111~113 (1997)
- Scarneciu I, "Efficacy of instillation treatment with hyaluronic acid in relieving symptoms in patients with BPS", IC and uncomplicated recurrent urinary tract infections-Long-term results of a multicenter study, 2019, pp.139, 105067~
- Lin CJ, "Changes in cystoscopic findings after intravesical hyaluronic acid instillation therapy in patients with interstitial cystitis", Diagnostics(Basel), 12, pp.2009~ (2022)
- Liu S, "Comparative effectiveness and safety of intravesical instillation treatment of interstitial cystitis", bladder pain syndrome : a systematic review and network metaanalysis of randomized controlled trials, 2021, pp.32, 1061~1071
- Hatina J, "Stem cells in the biology of normal urothelium and urothelial carcinoma", Neoplasma, 59, pp.728~736 (2012)
- Yang B, "In vitro comparative evaluation of recombinant growth factors for tissue engineering of bladder in patients with neurogenic bladder", J Surg Res, 186, pp.63~72 (2014)
- Ho PL, "Normal and neoplastic urothelial stem cells : getting to the root of the problem", Nat Rev Urol, 9, pp.583~594 (2012)
- Jiang YH, "Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis", bladder pain syndrome, 2013, pp.8, e76779~
- Jiang YH, "Urine oxidative stress biomarkers as novel biomarkers in interstitial cystitis", bladder pain syndrome, 2022, pp.10, 1701~
- Yang CH, "Dehydrated human amnion-chorion membrane extracts can ameliorate interstitial cystitis in rats by down-regulating inflammatory cytokines and protein coding genes : a preclinical study", Life(Basel), 12, pp.1693~ (2022)
- Konkol Y, "Intravesical treatment with cis-urocanic acid improves bladder function in rat model of acute bladder inflammation", Neurourol Urodyn, 35, pp.786~791 (2016)