Ulus Travma Acil Cerrahi Derg. 2022; 28(12): 1659-1666 | DOI: 10.14744/tjtes.2021.90140

Intraductal botulinum toxin injection suppressed the inflammation in experimental acute pancreatitis

Tonguç Utku Yýlmaz¹, Fatma Ceyla Eraldemir², Bora Gürel³, Ömer Yavuz⁴, Esra Acar⁵, Tonguç Ýþken⁶, Hasan Yýlmaz⁷, Nihat Zafer Utkan^2
1Department of Organ Transplantation, Acýbadem Mehmet Ali Aydýnlar University, Atakent Hospital, Ýstanbul-Türkiye
²Department of Biochemistry, Kocaeli University Faculty of Medicine, Kocaeli-Türkiye
³Institute of Cancer Research, Divison of Clinical Science, London-UK
⁴Department of General Surgery, Kocaeli University Faculty of Medicine, Kocaeli-Türkiye
⁵Department of Biochemistry, Kocaeli Health and Technology University Faculty of Pharmacy, Kocaeli-Türkiye
⁶Department of Plastic, Reconstructive and Aesthetic Surgery, Bahçeþehir University Faculty of Medicine, Ýstanbul-Türkiye
⁷Department of Gastroenterology, Kocaeli University Faculty of Medicine, Kocaeli-Türkiye

BACKGROUND: Acute pancreatitis (AP) is inflammation of pancreas in which pancreas enzymatic activity is increased. Parasym-pathetic innervation of pancreas plays an important role in several functions of pancreas. Botulinum toxin (BTx) might be a tool to suppress the pancreas activity in AP.
METHODS: In the preliminary experimental study, BTx (15U/kg) was administered directly and intraductal ways. After 10 days, blood amylase, lipase, trypsinogen, insulin, and glucagon levels were compared and no significant difference was seen between groups. Intraductal BTx administration is preferred for experimental AP model in rats; control, AP, intraductal BTx, and AP with Intraductal BTx (AP+BTx). AP was created by intraperitoneal injection of cerulean 20 µg/kg/injection (5 times). After 24 h, serum amylase, lipase, IL-6, IL-1β, TNF-α, and IL-10 were measured and pancreas tissue was evaluated for inflammation and necrosis.
RESULTS: Mean serum amylase, lipase IL-6, IL-1β, and TNF-α levels of the AP group were significantly higher compared to the other groups (p<0.05). However, there was no significant difference between the amylase and lipase levels of control, BTx, and AP+BTx groups. Serum insulin and glucagon levels in AP group were significantly higher than control and BTx groups (p<0.05). However, there is no significant difference between the insulin and glucagon levels of AP and AP+BTx groups. in pathological evaluation. In AP+ BTx group, there is less amount of centrilobular necrosis and there is mild inflammation and hyperplasia of pancreatic duct epithelium.
CONCLUSION: Administration of intraductal BTx suppressed the AP without making significant suppression in endogenous activity of pancreas.

Keywords: Acetylcholine, acute pancreatitis, botulinum toxin; cerulein; pancreas duct.

---

Deneysel akut pankreatit modelinde intraduktal botulinum toksin uygulamasý enflamasyonu baskýladý

Tonguç Utku Yýlmaz¹, Fatma Ceyla Eraldemir², Bora Gürel³, Ömer Yavuz⁴, Esra Acar⁵, Tonguç Ýþken⁶, Hasan Yýlmaz⁷, Nihat Zafer Utkan^2
1Acýbadem Mehmet Ali Aydýnlar Üniversitesi, Atakent Hastanesi, Organ Nakli Birimi, Ýstanbul
²Kocaeli Üniversitesi Týp Fakültesi, Biokimya Anabilim Dalý,Kocaeli
³Kanser Araþtýrma Merkezi, Klinik Bilimler, Londra, Ýngiltere
⁴Kocaeli Üniversitesi Týp Fakültesi, Genel Cerrahi Anabilim Dalý, Kocaeli
⁵Kocaeli Saðlýk ve Teknoloji Üniversitesi Eczacýlýk Fakültesi, Biyokimya Anabilim Dalý, Kocaeli
⁶Bahçeþehir Üniversitesi Týp Fakültesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalý, Ýstanbul
⁷Kocaeli Üniversitesi Týp Fakültesi, Gastroenteroloji Bilim Dalý, Kocaeli

AMAÇ: Akut pankreatit, pankreas enzim aktivitesinin arttýðý pankreas enflamasyonudur. Pankreasýn parasempatik uyarýmý, pankreasýn çeþitli fonksiyonlarýnda önemli rol oynar. Bu çalýþmanýn amacý, botulinum toksin’in (BTx), akut pankreatit’de pankreas aktivitesinin baskýlayabileceðini göstermektir.
GEREÇ VE YÖNTEM: Sýçanlarda deneysel ön çalýþmada 15 (u/kg) BTx, sýçan pankreasýna direkt veya intraduktal uygulandý. Kan amilaz, lipaz, tripsinojen, insülin ve glukagon seviyeleri 10 gün sonra ölçüldü ve anlamlý fark saptanmadý. Çalýþmaya klinik uygulanabilirlik açýsýndan akut pankreatit modelinde intraduktal BTx uygulama ile devam edildi. Kontrol, akut pankreatit (AP), intraduktal BTx ve akut pankreatit’de BTX (AP+BTx) gruplarý sekizer sýçandan oluþturuldu. Akut pankreatiti intraperitoneal cerulein (20µg/kg) ile saðlandý. Sýçanlar 24 saat sonra serum amilaz, lipaz, IL-6, IL-1β, TNF-α, ve IL-10 ölçümü için sakrifiye edildi. Pankreas dokularý enflamasyon ve nekroz incelemesi için alýndý.
BULGULAR: AP grubunda ortalama serum amilaz, lipaz, IL-6, IL-1β ve TNF-α deðerleri diðer gruplara göre anlamlý yüksek bulundu. Kontrol, BTx, AP+BTx gruplarý arasýnda ortalama serum amilaz ve lipaz deðerleri açýsýndan anlamlý fark saptanmadý. AP grubunda ortalama serum insulin ve gluka-gon deðerleri kontrol ve BTx grubuna göre anlamlý yüksek saptandý. Ortalama serum insülin ve glukagon düzeyleri AP ve AP+BTx gruplarý arasýnda anlamlý deðildi. Patolojik incemelede AP+BTx grubunda AP’ye göre daha az sentrilobüler nekroz, inflamasyon izlendi.
TARTIÞMA: Intraduktal BTx uygulamasý pankreas endojen aktivitesinde belirgin süpresyon yapmadan akut pankreatit’i baskýlamýþtýr.

Anahtar Kelimeler: Akut pankreatit, asetilkolin, botulinum toksin; pankreas kanalý; seruleim.

---

CITE