Evaluation of aromatase inhibitor on radiation induced pulmonary fibrosis via TGF- β/Smad 3 and TGF- β/PDGF pathways in rats

Abstract

Radiation-induced pulmonary fibrosis (RIPF) is a known complication in cancer patients after getting thoracic radiotherapy. Aromatase inhibitors (AIs) as anastrozole have been used instead of tamoxifen for adjuvant endocrine treatment of postmenopausal women with hormone sensitive breast cancer. This study is to evaluate the concurrent treatment of anastrozole and RIPF in rats. Twenty four female Wistar rats were distributed into 4 groups: Control (C), Radiation group (R) (total dose 30 Gy in 10 fractions, 5 fractions/week), anastrozole group (A) (0.003 mg/200 g body weight) orally for 14 consecutive days, and Radiation + anastrozole group (R + A). Radiation exposure resulted in a significant increase (p < 0.05) in pulmonary Transforming growth factor-beta 1 (TGF-β), SMAD family member 3 (Smad3), Platelet-derived growth factor (PDGF), malondialdehyde (MDA), Total nitrate/nitrite (NO), interleukin 1β (IL-1β) and interleukin 6 (IL-6) compared to the control group. While, significant decreases (p < 0.05) in superoxide dismutase (SOD) activity, reduced glutathione (GSH) and connective tissue growth factor (CTGF) were observed in lung tissue. These alterations were minimized by anastrozole intervention. Also, anastrozole markedly hindered the lung histopathological changes observed after radiation. Concomitant use of anastrozole with radiation seems to attenuate radiation-induced pulmonary toxicity via TGF-β/Smad 3 and TGF-β/PDGF pathways in rats.

Keywords:

• Radiation
• anastrazole
• TGF-β
• Smad 3
• PDGF

Acknowledgements

Authors acknowledge Prof. Ass. Dr. Sayed Abdel Raheem, Histopathology department, Faculty of Medicine, Al Azhar University, for accomplishing the examination of lung sections in the current study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

All authors participated equally in this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).