Role of nitric oxide and oxidative stress in pathophysiology of liver injury in streptozotocin-induced type 1 diabetic rats

Abstract

Type 1 diabetes mellitus (T1DM) is a severe chronic metabolic disorder characterized by hyperglycaemia because of the alterations in insulin secretion or its action. It is previously shown that hyperglycemia related oxidative stress (OS) and excessive nitric oxide (NO) production may cause severe complications in kidney and brain. In this report, it is aimed to investigate the cytotoxic effects of NO and to evaluate possible interaction with T1DM related hepatopathology. Expression levels of 8-hydroxy-2'deoxyguanosine (8-OHdG), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Cu/Zn superoxide dismutase (SOD1) and glutathione reductase (GR) were examined by immunohistochemistry in liver tissues. Results of the study revealed that levels of 8-OHdG (P<0.001), eNOS (P<0.001), eNOS (P<0.001), SOD1 (P<0.001) and GR (P<0.001) were remarkably higher in liver with T1DM than control. The most prominent finding of this study is the increased levels of 8-OHdG in the mostly hepatocyte cytoplasm. These results suggest an involvement of oxidative DNA damage and OS might play a pivotal role on hepatic degeneration and this is a novel insight of pathogenesis on the explanation of cellular processes in streptozotocin (STZ)-induced type 1 diabetic rats’liver. Furthermore, these results also suggested that STZ-induced hepatic pathology might have been augmented by the contribution of high NO expression mediated OS. Taken together, the results suggest NO related hepatic inflammation and degeneration closely implicated in pathophysiology of T1DM. The results also clearly indicated that OS plays an important role on hepatic pathology and OS biomarkers might indicate the progress of the T1DM

Keywords

• Hepatopathology
• nitric oxide
• oxidative stress
• type 1 diabetes mellitus

Streptozotosin ile tip 1 diyabet oluşturulan sıçanların karaciğerlerinde meydana gelen hasarlardanitrik oksit ve oksidatif stresin patofizyolojideki rolleri

Abstract

Tip 1 diyabet (T1D), insülinin salgı veya görevlerinde anormalliklerle karakterize kronik metabolik bir hastalıktır. Daha önceleri diyabetik hayvanlarda, hiperglisemi ile tetiklenen oksidatif stres (OS) ve nitrik oksit (NO) seviyelerindeki patolojik yükselmelerin böbrek ve beyinde şiddetli komplikasyonlara neden olduğunu gösterdik. Bu çalışma NO’in sitotoksik etkisinin ve OS’in T1D ile ilişkili hepatopatolojilerde herhangi bir ilişkinin olup olmadığını tanımlamak için tasarlanmıştır. Bu amaçla 8-hidroksi-2'deoxyguanosine (8-OHdG), endotelyal nitrik oksit sentaz (eNOS), uyarılabilir nitrik oksit sentaz (iNOS), Cu/Zn süperoksit dismutaz (SOD1) ve glutatyon redüktaz (GR) immunoreaktiviteleri karaciğer dokusunda araştırıldı. Çalışmada, 8-OHdG (P<0.001), eNOS (P<0.001), eNOS (P<0.001), SOD1 (P<0.001) ve GR (P<0.001) immunoreaktivitelerinin T1D’li hayvanlara ait karaciğer dokularında, sağlıklı kontrol gruplara göre ciddi anlamda bir artışın olduğu tespit edildi. Bu çalışmada en önemli bulgu, 8-OHdG sunumlarının genelde sitoplazmada olduğudur. Bu sonuçlar STZ ile indüklenen karaciğer dejenerasyonlarında OS’in ana kaynağının patolojik düzeylerde üretilen NO olduğunu da gösterdi. Ayrıca, oksidatif DNA hasarı ve oksidatif stresin diyabete bağlı karaciğer dejenerasyonlarında çok önemli bir rol aldığı ve hücresel mekanizmaların ortaya konmasında anahtar görevi üstleneceği gösterildi. Bu bulgular birlikte ele alındığında, T1D’le ilişkili karaciğer patolojileri NO aracılı karaciğer yangıları ve dejenerasyonların önemli bir faktör olduğu görülmektedir. Ayrıca, bu çalışma OS’in karaciğer patofizyolojisinde görev aldığını ve OS belirleyicilerinin hastalığın takibinde önemli görevler alabileceğini gösterdi

Keywords

• Hepatopatoloji
• nitrik oksit
• oksidatif stres
• tip 1 diyabet

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