Publication: Sıçanda indometazin ve etanol ile indüklenen mide ülseri modellerinde metforminin etkisinin araştırılması
Abstract
Amaç: Tip 2 diabetes mellitus tedavisinde yaygın kullanılan metformin ön tedavisininfarklı mide ülseri modelleri üzerine etkisini incelemektir.Gereç ve yöntem: Erkek Sprague-Dawley sıçanlarda (280-450 gr) oral yolla indometazin (80 mg/ kg) veya absolut etanol (5 ml/ kg) uygulanarak iki farklı ülser modeli oluşturuldu. Metformin (500 mg/ kg) veya ranitidin (50 mg/ kg) oral olarak ülserojenik ajanlardan önce üç gün boyunca verildi. Üçüncü günde dekapitasyonun ardından mideler makroskopik ve mikroskopik olarak değerlendirildi. Oksidan ve anti-oksidan parametreler tayin edildi ve apoptoz değerlendirildi. Serumda sitokin düzeyleri ölçüldü. Farklı grup sıçanlarda dekapitasyon öncesi lazer doppler akımölçer ile mide kan akımı ölçüldü. İstatistiksel analizde tek yönlü ANOVA ve Tukey-Kramer çoklu karşılaştırma testi kullanıldı. Anlamlılık düzeyi p<0,05 olarak kabul edildi.Bulgular: Metformin etanol grubunda lezyonları makroskopik (p<0,001) ve mikroskopik (p<0,01) düzeyde azalttı. Etanol grubunda kontrole göre artan kemiluminisans metformin tedavisi ile azalırken (p<0,05 ve p<0,001), mide kan akımı tedavisiz grubuna kıyasla artış gösterdi (p<0,01). Etanol grubunda artan lipit peroksidasyonu metformin ile düştü (p<0,01). Etanol grubunda kontrole kıyasla yüksek olan apoptotik indeks (p<0,001), metformin ile düşme gösterdi (p<0,001). İndometazin grubunda ise, metformin lezyonları mikroskopik düzeyde azalttı (p<0,05). İndometazin grubunda artmış kemiluminisans metformin ile azalırken (p<0,01 ve p<0,05) mide kan akımı tedavisiz gruba göre arttı (p<0,05). Apoptotik indeks, metformin alan indometazin grubunda tedavisiz gruba göre anlamlı olarak düşüktü (p<0,001). İndometazin grubunda anlamlı şekilde azalan (p<0,01) glutatyon,metformin ile artış gösterdi (p<0,05).Sonuç: Metformin ön tedavisi iki farklı mide ülseri modelinde kısmi koruma sağladı. Bu korumada olası mekanizmalar arasında oksidan oluşumunda ve apoptozda azalma ve mide kan akımında artma yer almaktadır.
Aim: To examine the effect of metformin -widely used in the treatment of type II diabetes mellitus- pre-treatment on different gastric ulcer models.Material and method: Two different ulcer models were induced in male Sprague- Dawley rats (280-450 g) by indomethacin (80 mg/ kg) or absolute ethanol (5 ml/ kg) given orally. Metformin (500 mg/ kg) or ranitidine (50 mg/ kg) was administered orally for three days prior to ulcerogenic agents. After decapitation on day-3, stomachs were evaluated macroscopically and microscopically. Oxidant and antioxidant parameters were determined and apoptosis was evaluated. Cytokine levels were measured in the serum. Gastric blood flow was measured via laser-doppler flowmeter before decapitation in other groups of rats. One-way ANOVA and Tukey-Kramer multiple comparison tests were used for statistical analysis. p<0,05 was considered significant.Results: Metformin reduced lesions macroscopically (p<0,001) and microscopically (p<0,1) in ethanol groups. While chemiluminescence increased in ethanol group compared to control showed a reduction with metformin (p<0,05 and p<0,001), gastric blood flow increased compared to untreaed group (p<0,01). Increased lipid peroxidation in ethanol group was reduced by metformin (p<0,01). Apoptotic index (p<0,001), which was higher in ethanol group compared to control, diminished by with metformin (p<0,001). In indomethacin group, metformin reduced lesions microscopically (p<0,05). While high chemiluminescence in indomethacin group decreased by metformin (p<0,01 and p<0,05), gastric blood flow improved compared to untreated group (p<0,05). Apoptotic index was lower in metformin administered indomethacin group than untreated group (p<0,001). Glutathione which decreased in indomethacin group (p<0,01) was restored by metformin (p<0,05).Conclusion: Metformin pre-treatment provided partial protection in two different gastric ulcer models. Possible mechanisms for this protection include decrease in oxidant formation and apoptosis and increase in gastric blood flow.
Aim: To examine the effect of metformin -widely used in the treatment of type II diabetes mellitus- pre-treatment on different gastric ulcer models.Material and method: Two different ulcer models were induced in male Sprague- Dawley rats (280-450 g) by indomethacin (80 mg/ kg) or absolute ethanol (5 ml/ kg) given orally. Metformin (500 mg/ kg) or ranitidine (50 mg/ kg) was administered orally for three days prior to ulcerogenic agents. After decapitation on day-3, stomachs were evaluated macroscopically and microscopically. Oxidant and antioxidant parameters were determined and apoptosis was evaluated. Cytokine levels were measured in the serum. Gastric blood flow was measured via laser-doppler flowmeter before decapitation in other groups of rats. One-way ANOVA and Tukey-Kramer multiple comparison tests were used for statistical analysis. p<0,05 was considered significant.Results: Metformin reduced lesions macroscopically (p<0,001) and microscopically (p<0,1) in ethanol groups. While chemiluminescence increased in ethanol group compared to control showed a reduction with metformin (p<0,05 and p<0,001), gastric blood flow increased compared to untreaed group (p<0,01). Increased lipid peroxidation in ethanol group was reduced by metformin (p<0,01). Apoptotic index (p<0,001), which was higher in ethanol group compared to control, diminished by with metformin (p<0,001). In indomethacin group, metformin reduced lesions microscopically (p<0,05). While high chemiluminescence in indomethacin group decreased by metformin (p<0,01 and p<0,05), gastric blood flow improved compared to untreated group (p<0,05). Apoptotic index was lower in metformin administered indomethacin group than untreated group (p<0,001). Glutathione which decreased in indomethacin group (p<0,01) was restored by metformin (p<0,05).Conclusion: Metformin pre-treatment provided partial protection in two different gastric ulcer models. Possible mechanisms for this protection include decrease in oxidant formation and apoptosis and increase in gastric blood flow.