Publication: Sıçanda stres ile uyarılan mide ülserinde simvastatin'in etkisi
Abstract
Amaç: Bu çalışmada sıçanlarda stres ile uyarılan mide ülserinde simvastatin (SİM)'in olası koruyucu etkisini değerlendirmek amaçlanmıştır. Gereç ve Yöntem: Sprague-Dawley sıçanlarda (250-300 gr) soğuk-kısıtlama stresi uygulaması ile mide ülseri oluşturuldu. Stres öncesi 21 gün süreyle SİM (10 mg/kg/gün; oral yolla) veya fizyolojik tuzlu su (1 ml; oral yolla) uygulandı. Bir grup sıçan 21. günde SİM öncesi selektif olmayan nitrik oksit sentaz (NOS) inhibitörü L-NAME (50 mg/kg; intraperitoneal) veya selektif olmayan siklooksijenaz (COX) inhibitörü indometazin (İndo; 5 mg/kg; subkutan) verildi. Mideler makroskopik ve mikroskopik olarak incelendi ve biyokimyasal analizler için saklandı.Bulgular: Stres grubunda lezyonların şiddeti SİM ile azaldı ancak L-NAME veya İndo ile anlamlı bir değişiklik göstermedi. Stres mide miyeloperoksidaz aktivitesini kontrol düzeyine kıyasla artırdı (p<0,01); ancak, SİM bu parametre üzerinde anlamlı bir değişikliğe neden olmadı. Stres mide kemiluminisans düzeylerini artırdı (p<0,01); bu etki SİM ile geri döndürüldü (p<0,001); L-NAME veya İndo ile tedavi edilen hayvanlarda ise devam etti. Sonuç: Soğuk-kısıtlama stresine maruz bırakılan sıçanlara SIM öntedavisi mide lezyon oluşumunda NOS ve COX sistemlerinden ayrı mekanizmalarla nötrofil dışı hücrelerden kaynaklanan oksidanları baskılayarak kısmen koruma sağlamaktadır.
Objectives: This study aimed to elucidate the possible protective effect of simvastatin (SIM) pretreatment on stress-induced gastric ulcer in rats. Materials and Methods: Gastric ulcer was produced in Sprague-Dawley rats (250-300 g) by cold-restraint stress. SIM (10 mg/kg/day; per oral) or saline was administered for 21 days prior to stress. On day-21, a group of animals was treated with the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (50 mg/kg; intraperitoneally) or the non-selective cyclooxygenase (COX) inhibitor indomethacin (Indo; 5 mg/kg; subcutaneously) prior to SIM. The stomachs were examined macroscopically and microscopically and stored for biochemical analyses.Results: The severity of the lesions of the stress group was decreased by SIM, but this was not altered significantly by L-NAME or Indo. Stress increased gastric myeloperoxidase activity compared to control level (p<0.01); however, SIM did not cause a significant change on this parameter. Stress increased gastric chemiluminescence levels (p<0.001) which were reversed by SIM (p<0.001) and this effect continued in L-NAME- or Indotreated animals. Conclusion: SIM pretreatment of rats with cold-restraint stress provided partial protection against gastric lesion formation via suppression of oxidants derived from sources other than neutrophils without the involvement of NOS and COX systems.
Objectives: This study aimed to elucidate the possible protective effect of simvastatin (SIM) pretreatment on stress-induced gastric ulcer in rats. Materials and Methods: Gastric ulcer was produced in Sprague-Dawley rats (250-300 g) by cold-restraint stress. SIM (10 mg/kg/day; per oral) or saline was administered for 21 days prior to stress. On day-21, a group of animals was treated with the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (50 mg/kg; intraperitoneally) or the non-selective cyclooxygenase (COX) inhibitor indomethacin (Indo; 5 mg/kg; subcutaneously) prior to SIM. The stomachs were examined macroscopically and microscopically and stored for biochemical analyses.Results: The severity of the lesions of the stress group was decreased by SIM, but this was not altered significantly by L-NAME or Indo. Stress increased gastric myeloperoxidase activity compared to control level (p<0.01); however, SIM did not cause a significant change on this parameter. Stress increased gastric chemiluminescence levels (p<0.001) which were reversed by SIM (p<0.001) and this effect continued in L-NAME- or Indotreated animals. Conclusion: SIM pretreatment of rats with cold-restraint stress provided partial protection against gastric lesion formation via suppression of oxidants derived from sources other than neutrophils without the involvement of NOS and COX systems.