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

Year 2018, , 402 - 413, 15.12.2018

Mehmet Eray Alçığır , Ceyda Tuba Şengel Türk , Okan Ekim Canan Hasçiçek

https://doi.org/10.30607/kvj.437999

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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