The histologic evaluation of Atorvastatin and Melatonin treatment on oxidative stress and apoptosis of diabetic rat pancreas

In the diabetic state, there is an enhanced oxidative stress due to excessive production of reactive oxygen compounds and decreased bioavailability of nitric oxide. Antioxidant treatment has been used to prevent oxidative damage in diabetes. The objective of the present study was to explore the effects of atorvastatin (AT) and melatonin (MLT) on oxidative stress in diabetic rat pancreas. We also assessed nitric oxide synthase (NOS) activity and apoptosis. Diabetes was induced by an alkylating agent steptozotocin (STZ, 55 mg/kg, IP). Six weeks later rats were divided into five groups: STZ-induced diabetic group received atorvastatin (STZ+AT), STZ-induced diabetic group received melatonin (STZ+MLT) and STZ-induced diabetic group received atorvastatin and melatonin (STZ+AT+MLT). The vehicle-treated non-diabetic (CT) and diabetic group (STZ-CT) served as normoglycemic and diabetic controls. AT was given 8 mg/kg orally and MLT was given 10 mg/kg/IP once a day for 2 weeks beginning from the sixth week. Pancreatic tissue was examined by immunohistochemical methods. Although no significant difference was observed with respect to antioxidant status, NOS activity was tended to be higher in the untreated diabetic rats than in the treated rats. We observed that AT and MLT treatment improved the histopathological changes including apoptosis and oxidative stress in diabetic pancreas. Diyabette reaktif oksijen bileşiklerinin aşırı üretimi ve nitrik oksidin azalmış biyoyararlanımına bağlı olarak oksidatif stres artmaktadır. Antioksidan tedavi diyabette oksidatif hasarı önlemek için kullanılmaktadır. Bu araştırmanın amacı, atorvastatin (AT) ve melatonin (MLT) tedavisinin oksidatif stres üzerine etkilerini diabetik sıçan pankreasında araştırmak, nitrik oksid sentaz (NOS) aktivitesi ve apoptoz ile ilişkisini değerlendirmektir. Diyabet oluşumu tek doz streptozotozin (STZ, 55 mg/kg, IP) ile indüklendi. 6 hafta sonra sıçanlar 5 gruba ayrıldı. AT uygulanan diyabetik grup (STZ+AT), MLT uygulanan diyabetik grup (STZ+MLT), AT ve MLT uygulanan diyabetik grup (STZ+AT+MLT). Kontrol ve diyabetik kontrol grupları da oluşturulmuştur. AT 8 mg/kg oral yoldan uygulanmış, MLT ise 10 mg/kg/gün olarak 6. haftadan başlayarak 2 hafta boyunca IP yolla uygulanmıştır. Pankreas dokusu immunohistokimyasal yöntemlerle incelenmiştir. Antioksidan durumla ilgili olarak belirgin bir farklılık gözlenmemekle birlikte, NOS aktivitesi tedavi almayan diyabetik sıçanlarda tedavi alan gruplara göre daha yüksek o