Nesfatin-1: Does it Have Therapeutic Potential for Cyclophosphamide-Induced Interstitial Cystitis?

Öz

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a clinical condition characterized by symptoms such as frequent urination, suprapubic or pelvic pain, and decreased urine output. Inflammation is a significant contributor to the pathophysiology of this disease. Recent research has also highlighted the potent anti-apoptotic and antioxidant properties of nesfatin-1(NES) which is a hypothalamic neuropeptide. This study aimed to investigate the anti-inflammatory, anti-apoptotic, and antioxidant effects of NES in a cyclophosphamide (CYP)-induced IC model in rats. In this study female Sprague Dawley rats (n=32) were randomly assigned to four groups: control, CYP, CYP+NES 5 μg/kg, and CYP+NES 10 μg/kg. BPS/IC was induced by administering a single intraperitoneal (i.p.) dose of 70 mg/kg of CYP every three days for 12 days. The effects of NES were assessed using behavioral tests, histological examination, histopathological analyses, and biochemical analyses of bladder tissue.NES at a dose of 5 μg/kg and 10 μg/kg significantly reduced bladder pain as measured by the von Frey test. It showed partially protective effects against CYP-induced BPS/IC as evidenced by reduced histological and histopathological damage to the bladder, by way of suppression of oxidative stress markers and a decrease in inflammatory burden. Notably, the 5 μg/kg dosage of NES proved to be more effective than the 10 μg/kg dosage.In summary, these preclinical findings suggest that NES holds promise as a therapeutic agent for the treatment of CYP-induced BPS/IC. Nonetheless, further preclinical and clinical investigations are warranted to substantiate its efficacy and safety.

Anahtar Kelimeler

• Bladder pain syndrome
• Cyclophosphamide
• Interstitial cystitis
• Nesfatin-1
• Rat.

Destekleyen Kurum

This study was supported by Kütahya Health Sciences University, Scientific Research Projects coordinatorship. Project Number: TSA-2022-113.

Proje Numarası

Project Number: TSA-2022-113.

Etik Beyan

The study was approved by Local Ethics Committee for Animal Experiments of XXX. Approval Number: 2022-04-01; Approval Date: 21.04.2022

Nesfatin-1: Siklofosfamid kaynaklı interstisyel sistit için terapötik potansiyeli var mı?

Öz

Mesane ağrısı sendromu/interstisyel sistit (BPS/IC), sık idrara çıkma, suprapubik veya pelvik ağrı gibi belirtilerle karakterize edilen bir klinik durumdur. Enflamasyon, bu hastalığın patofizyolojisinde önemli bir rol oynar. Son zamanlarda yapılan araştırmalar, hipotalamik bir nöropeptid olan nesfatin-1 (NES)’in güçlü anti-apoptotik ve antioksidan özelliklerini de ortaya koymuştur. Bu çalışma, sıçanlarda siklofosfamid (CYP) ile indüklenen IC modelinde NES’in anti-enflamatuar, anti-apoptotik ve antioksidan etkilerini araştırmayı amaçlamıştır. Çalışmada dişi Sprague Dawley sıçanları (n=32) rastgele dört gruba ayrılmıştır: kontrol, CYP, CYP+NES 5 μg/kg ve CYP+NES 10 μg/kg. BPS/IC, 12 gün boyunca her üç günde bir 70 mg/kg CYP'nin tek bir intraperitoneal (i.p.) dozunun uygulanmasıyla indüklendi. NES'in etkileri, davranış testleri, histolojik inceleme, histopatolojik analizler ve mesane dokusunun biyokimyasal analizleri kullanılarak değerlendiridi. 5 μg/kg ve 10 μg/kg dozlarındaki NES, von Frey testi ile ölçülen mesane ağrısını önemli ölçüde azalttı. Mesanede histolojik ve histopatolojik hasarın azalması, oksidatif stres belirteçlerinin baskılanması ve inflamatuar yükün azalmasıyla kanıtlandığı üzere, CYP kaynaklı BPS/IC’ye karşı kısmen koruyucu etkiler gösterdi. Özellikle 5 μg/kg’lık NES dozunun, 10 μg/kg’lık dozdan daha etkili olduğu ortaya çıktı. Özetle, preklinik bulgular, nesfatin-1’in CYP kaynaklı BPS/IC tedavisi için umut vaat eden bir terapötik ajan olduğunu göstermektedir. Bununla birlikte, etkinliğini ve güvenliğini doğrulamak için daha fazla preklinik ve klinik araştırmaların yapılması gerekmektedir. 

Anahtar Kelimeler

• Mesane ağrısı sendromu
• Siklofosfamid
• İnterstisyel sistit
• Nesfatin-1
• Sıçan.

Destekleyen Kurum

Bu çalışma, Kütahya Sağlık Bilimleri Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından desteklenmiştir. Proje Numarası: TSA-2022-113.

Proje Numarası

Project Number: TSA-2022-113.

Etik Beyan

Bu çalışma, Kütahya Sağlık Bilimleri Üniversitesi, Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmıştır. Onay Numarası: 2022-04-01; Onay Tarihi: 21.04.2022

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