Publication: Phoenixin-14’ün sıçanlarda pankreatikobilier kanal ligasyonu ve safra kanalı ligasyonu ile oluşturulan pankreatikobilier inflamasyon modelinde olası koruyucu etkinliğinin araştırılması
Abstract
Amaç: Safra yolu obstrüksiyonu hepatit ve akut pankreatite yol açar. Phoenixin (PNX) hipotalamusta üretilen anti-inflamatuvar ve antioksidan özellikte bir peptiddir. Safra kanalı (BDL) ile safra ve pankreas kanalı (PBDL) bağlanarak oluşturulan hepatit ve pankreatit modelinde PNX’in olası koruyucu etkisini araştırmayı amaçladık. Gereç ve Yöntem: Erkek Sprague Dawley sıçanlara ketamin anestezisi altında BDL (n=16), PBDL (n=16) ve yalancı bağlama (C, kontrol n=8) ameliyatları yapıldı. Operasyondan hemen sonra ve izleyen 2 gün PNX-14 (50 µg/ kg/ gün)/ serum fizyolojik (SF) cilt altına verildi. Postoperatif 72. saatte lazer Doppler akımölçer ile karaciğer ve böbrek kan akımı ölçüldü. Kalp kanı alınarak sakrifikasyon yapıldı. Karaciğer, pankreas, böbrek, akciğer, beyin dokularında mikroskopik hasar, reaktif oksijen türleri (ROS) miktarı, miyeloperoksidaz (MPO), glutatyon (GSH) ve lipid peroksidasyon (LP) aktivitesi, kaspaz-3 ve 8-hidroksi-deguanosin (8-OH-dG) miktarı değerlendirildi. Serumda proinflamatuvar sitokinler tayin edildi. Sonuçlar ortalama±standart hata olarak belirtildi, ANOVA ile karşılaştırıldı p<0.05 ise anlamlı sayıldı Bulgular: BDL operasyonu karaciğerde, PBDL operasyonu karaciğer ve pankreasta mikroskopik hasar skorunu, artırdı. PNX-14 tedavisi hasarı iyileştirdi. Karaciğer ve böbrek kan akımı PBDL grubunda anlamlı derecede azalıp PNX tedavisiyle kontrol değerine döndü. Karaciğer GSH miktarı BDL grubunda PNX ile arttı. PBDL grubunda artan serum TNF-seviyesi PNX tedavisiyle azaldı, serum IL-1 seviyesi değişmedi. Karaciğer ve pankreastaki kaspaz 3, 8-OH-dG, MPO ve LP miktarları bütün gruplarda benzerdi, Operasyon gruplarında karaciğer ve pankreasta gözlenen ROS artışı PNX tedavisi ile geriledi. PNX akciğerde artan lucigenin miktarını azalttı, beyinde ROS miktarını değiştirmedi. Sonuç: PNX, kolestatik hepatit ve pankreatiti ROS üretimini azaltarak, karaciğer antioksidan kapasitesini ile karaciğer ve böbrek kan akımını artırarak tedavi eder.
Objective: Bile duct obstruction, which results in cholestatic liver injury, is the major cause of acute pancreatitis. Phoenixin (PNX), is a hypothalamic peptide, exerts antioxidant and anti-inflammatory effects. We evaluated possible therapeutic effects of PNX on hepatic and pancreatic damage induced by biliary (BDL) or pancreaticobiliary duct (PBDL) obstruction Materials and Methods: In male Sprague Dawley rats, BDL (n=16), PBDL (n=16) or sham-surgery (control, n=8) was performed. Either PNX-14 (50 µg/ kg/ day) or saline was subcutaneously injected immediately after surgery and in the following 2 days. On the post-operative 3rd day, hepatic and renal blood flow was measured using laser Doppler flowmeter Rats were euthanized. Microscopic damage, reactive oxygen species (ROS), myeloperoxidase activity (MPO), antioxidant capacity (GSH), lipid peroxidation products (LP), were measured in liver, pancreas, kidney, brain, lung samples. Serum proinflammatory cytokine levels were determined. Data was expressed as mean ±standard error, analysed by using ANOVA. p<0.05 accepted as significant. Results: Increased microscopic damage scores in the pancreas of PBDL and in the liver of BDL group were reduced by PNX-14 treatment. Hepatic glutathione level was elevated in PNX-14-treated operation groups. PBDL significantly reduced hepatic and renal blood flow, while PNX-14 reversed blood flow in both organs back to control levels. Elevated ROS levels in both hepatic and pancreatic tissues of saline-treated operation groups were reduced in PNX-treated groups. Conclusion: Cholestatic liver injury and bile-induced pancreatic injury are alleviated by PNX-14 treatment, which acts via its ROS scavenging activity, by replenishing hepatic antioxidant capacity and restoring impaired organ perfusion.
Objective: Bile duct obstruction, which results in cholestatic liver injury, is the major cause of acute pancreatitis. Phoenixin (PNX), is a hypothalamic peptide, exerts antioxidant and anti-inflammatory effects. We evaluated possible therapeutic effects of PNX on hepatic and pancreatic damage induced by biliary (BDL) or pancreaticobiliary duct (PBDL) obstruction Materials and Methods: In male Sprague Dawley rats, BDL (n=16), PBDL (n=16) or sham-surgery (control, n=8) was performed. Either PNX-14 (50 µg/ kg/ day) or saline was subcutaneously injected immediately after surgery and in the following 2 days. On the post-operative 3rd day, hepatic and renal blood flow was measured using laser Doppler flowmeter Rats were euthanized. Microscopic damage, reactive oxygen species (ROS), myeloperoxidase activity (MPO), antioxidant capacity (GSH), lipid peroxidation products (LP), were measured in liver, pancreas, kidney, brain, lung samples. Serum proinflammatory cytokine levels were determined. Data was expressed as mean ±standard error, analysed by using ANOVA. p<0.05 accepted as significant. Results: Increased microscopic damage scores in the pancreas of PBDL and in the liver of BDL group were reduced by PNX-14 treatment. Hepatic glutathione level was elevated in PNX-14-treated operation groups. PBDL significantly reduced hepatic and renal blood flow, while PNX-14 reversed blood flow in both organs back to control levels. Elevated ROS levels in both hepatic and pancreatic tissues of saline-treated operation groups were reduced in PNX-treated groups. Conclusion: Cholestatic liver injury and bile-induced pancreatic injury are alleviated by PNX-14 treatment, which acts via its ROS scavenging activity, by replenishing hepatic antioxidant capacity and restoring impaired organ perfusion.