Studien zur Untersuchung von F2-Isoprostanen und 8-epi-PGF2α als Marker für oxidativen Stress bei Typ 1 Diabetes

Diabetes mellitus gewinnt aufgrund steigender Fallzahlen und der dadurch bedingten Zunahme der Komplikationen, die durch die Erkrankung hervorgerufen werden, immer mehr an Bedeutung. Als ein möglicher Faktor für die Enstehung der Erkrankung und Folgeschäden wird oxidativer Stress diskutiert. Im Rahm...

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Bibliographic Details
Main Author: Gerstner, Anemone
Contributors: Nüsing, Rolf (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2013
Online Access:PDF Full Text
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Diabetes mellitus gains due to rising numbers of cases and the consequent increase of the complications caused by the disease, more and more importance. As a possible factor for the emergence of the disease and consequential complications oxidative stress is discussed. In the context of oxidative stress free radicals cause damage to proteins, lipids and DNA. In this respect, a valid marker for the detection of these changes would be desirable. A previously applied parameter for lipid oxidation is the MDA, which is determined from the patient's serum. In addition, in recent years certain F2- isoprostanes from the urine are postulated as a reliable marker of oxidative stress. The present work consists of a clinical part and experimental animal studies. At first, studies of children with type 1 diabetes have been carried out. This was followed by additional studies on various mouse populations. For this purpose, relevant laboratory parameters were analyzed, such as blood glucose, HbA1c, F2-isoprostanes, 8-epi-PGF2α and MDA. The clinical study shows that both MDA and F2-isoprostanes are increased in children with type 1 diabetes compared to a healthy population. It can be a significant correlation found for HbA1c only for the F2-isoprostanes. The experimental animal studies confirm these results. In addition, the results of animal experiments show, that the absence of the isoenzyme COX-1 has no influence on the course of disease. The absence of COX-2 leads to premature decease of the animals. The reason may lie in an increased sensitivity of the pancreas of the streptozotocin-applied due to the lack of COX-2 isoenzyme . Furthermore, the results indicate that the isoenzyme COX-2 plays an essential role in the formation of 8-epi-PGF2α. For other isoprostanes, a radical-mediated formation is discussed. Under the administration of the antioxidant Tempol there is a reduction of lipid oxidation (MDA, F2-isoprostanes), but without improvement of blood glucose, diuresis and proteinuria. Treatment options by means of antioxidants should be discussed further in so far as the present data are controversial. Finally, reasonable doubts remain whether the F2-isoprostanes as markers of oxidative stress in type 1 diabetes actually deliver meaningful results regarding to the extent of the disease.