Radix Angelica Sinensis and Radix Hedysari Ultrafiltration Extract Protects against X-Irradiation-Induced Cardiac Fibrosis in Rats.

Chengxu Ma,Huiping Wei,Zhaoyuan Fu,Yingdong Li,Xinke Zhao,Huan Guo,Juan Chang

doi:10.1155/2020/4675851

Abstract

Radiation-induced myocardial fibrosis (RIMF) is the main pathological change associated with radiation-induced heart toxicity after radiation therapy in patients with thoracic tumors. There is an antifibrosis effect of Radix Angelica Sinensis and Radix Hedysari (RAS-RH) ultrafiltration extract from Danggui Buxue decoction (DBD) in X-irradiation-induced rat myocardial fibrosis, and this study aimed to investigate whether that effect correlated with apoptosis and oxidative stress damage in primary rat cardiac fibroblasts; further, the potential mechanisms were also explored. In this study, we first found that the RAS-RH antifibrosis effect was associated with the upregulation of microRNA-200a and the downregulation of TGF-β1/smad3 and COL1α. In addition, we also found that the antifibrosis effect of RAS-RH was related to the induction of apoptosis in primary rat cardiac fibroblasts and to the prevention of damage caused by reactive oxygen species (ROS). Interestingly, primary rat cardiac fibroblasts exposed to X-ray radiation underwent apoptosis less frequently in the absence of RAS-RH. Therefore, RAS-RH has the ability to protect against fibrosis, which could be occurring through the induction of apoptosis and the resistance to oxidative stress in rats with X-irradiation-induced myocardial fibrosis; thus, in a model of RIMF, RAS-RH acts against X-irradiation-induced cardiac toxicity.

Highlights

Radiation-induced heart disease (RIHD) is associated with mortality and morbidity in patients with thoracic malignancies who undergo radiotherapy (RT), and RIHD limits the effect of tumor management
Cardiac histology from the control appeared morphologically normal, whereas in the X-ray radiation group, inflammatory infiltration was observed by Hematoxylin and eosin (H&E) staining, and myocardial fibrosis and irregular collagen deposition in the hearts were shown by Masson’s trichrome staining. e histology of heart tissue from the Radix Angelica Sinensis and Radix Hedysari (RAS-RH) + X-ray group showed less inflammatory infiltration and myocardial fibrosis than what was observed in the X-ray radiation group. ese results indicated that X-ray radiation can induce significant myocardial fibrosis, and 50 mg/kg/day of RAS-RH partially reduced X-ray-induced fibrosis
As active TGF-β1 plays a major role in X-irradiationinduced myocardial fibrosis, we investigated serum TGF-β1 amount by Enzyme-linked immunosorbent assay (ELISA), and as shown in Figure 1(e), TGF-β1 amount was significantly increased in the X-ray radiation group compared with that of the control group (6841.944 ± 283.360 pg/mL vs. 4504.815 ± 103.948 pg/mL, P < 0.01)

Summary

Introduction

Radiation-induced heart disease (RIHD) is associated with mortality and morbidity in patients with thoracic malignancies who undergo radiotherapy (RT), and RIHD limits the effect of tumor management. Cardiac fibroblasts exposed to radiation play a vital role in proliferation, apoptosis, and oxidative damage, and they secrete collagen and extracellular matrix [3]; further, early macrophage-rich plaques form in the intima of the vessel wall after radiation [4]. Radiation can accelerate the development of coronary artery disease and diffuse interstitial fibrosis of the myocardium with endothelial cell effacement [5], which is a typical manifestation of radiation-induced myocardial fibrosis (RIMF). ROS directly activate TGF-β1/smad, which promotes fibroblast proliferation and eventually diffuse fibrosis in heart tissue. Circulating microRNA-200a may represent a biomarker for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy [7], and it may protect against apoptosis by inhibiting ROS in cardiomyocytes [8].

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