Yetişkin ve Kastre Edilmiş Erkek Ratlarda Yüksek Doz Testosteron Propiyonatın İndüklediği Kardiyak Fibrozis Üzerine Lonidamin Yüklü Lipit-Polimer Hibrit Nanopartiküllerin Etkisi

Abstract

In recent years, the usage of exogenous testosterone has tripled in humans. Although, mechanism has not yet been fully elucidated, there is a correlation between the increased risk of heart failure and testosterone usage. The aim of this study was to demonstrate cardiac fibrosis, which a main finding of hearth failure, in testosterone propionate-applied male rats and to show its regression by Lonidamine as an anti-hyperplastic agent. A total of 72 adult Wistar albino and neutralized male rats were divided into 4 groups (n=18 in each groups). Animals in all groups were received to testosterone propionate until 2nd, 4th, and 12th weeks (n=6 in each groups). Subsequently, group I and II also received the pure solution of Lonidamine hydrochloride and its lipid-polymer hybrid nanoparticulate formulation via intraprostatic injection. Group III, blank lipid-polymer hybrid nanoparticle formulation were solely administrated via same way. The control group or group IV were received only testosterone. At the end of the experiment period, hearts were collected and fibrocytic changes were confirmed by histochemical and immunohistochemical methods. Histopathologically, fibrosis were lower in group I and II when comprared to that of group III and IV. Imunohistochemically, bFGF, cyclin D1 and p16 protein expressions were evaluated. bFGF and cyclinD1 epxressions correspondingly to increasing fibrosis were found higher in last two groups during the experiment. But, p16 expressions were lower in Lonidamine treated-group I and II. In conclusion, results of this study supported that testosterone propionate may promote cardiac fibrosis. Lonidamine hydrochloride may be used in its prevention of fibrosis.