Effects of Lonidamine-Loaded Lipid-Polymer Hybrid Nanoparticles on Cardiac Fibrosis Induced By High-Dose Testosterone Propionate In Adult and Neutered Male Rats

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. 

Keywords

• Cardiac fibrosis,Lonidamine hydrochloride,Testosterone,Rat

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

Abstract

Son yıllarda, insanlarda ekzojen testosteron kullanımı üç katına çıkmıştır. Mekanizma henüz tam olarak aydınlatılmamış olmasına rağmen kalp yetmezliği riskini arttırdığına dair bir korelasyon vardır. Bu çalışmanın amacı, erkek sıçanlarda testosteron propiyonat kullanımının kalp yetmezliğinin temel bulgusu olan fibrozise yol açtığını ve bir anti-hiperplastik ajan olan Lonidaminin bunu geriletici etkisini göstermekti. Çalışmada, toplam 72 adet kastre edilmiş, yetişkin Wistar albino erkek sıçan kullanıldı ve hayvanlar 4 ana gruba ayrıldı (her bir grupta için n= 18).  Bu ana gruplar 3 alt gruba ayrılarak (n=6 her bir grup için) hayvanlara, 2., 4. ve 12. haftalara kadar testosteron propiyonat uygulandı. Group I ve II için, Lonidamin hidroklorür, saf çözelti içinde ve bunun lipit-polimer hibrit nanopartikül formülasyonu halinde prostatlara enjekte edildi. Grup III için sadece lipit-polimer hibrit nanopartikül formülasyonu uygulandı. Kontrol grubu olarak grup IV’de sadece testesteron uygulandı. Çalışmanın sonunda kalpler toplandı. Histopatolojik olarak fibrosis grup I ve II’de grup III ve IV’dekiyle karşılaştırıldığında daha düşüktü. İmmünohistokimyasal olarak bFGF, siklin D1 ve p16 protein ekspresyonları değerlendirildi. Son iki grupta, artan fibrozise karşılık gelen bFGF ve siklinD1 ifadeleri, deney sırasında daha yüksek bulundu. Ancak, p16 ifadeleri Lonidamin uygulanan grup I ve grup II’de daha düşüktü. Sonuç olarak, bu sonuçlar testosteron propiyonatın kardiyak fibrozisi etkileyebileceğini desteklemektedir ve fibrozisin önlenmesinde Lonidamin hidroklorür kullanılabilir.

Keywords

• Kardiyak fibrozis,Lonidamin hidroklorür,Testosteron,Sıçan

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