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Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury.
Life Sci. 2020 Aug 15; 255:117743.LS

Abstract

AIMS

Radiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms.

MAIN METHODS

BALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-β; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot.

KEY FINDINGS

The results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-β with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined.

SIGNIFICANCE

2ME2 is a promising radioprotectant with fewer anticipated side effects.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt. Electronic address: mohamed.saleh@nub.edu.eg.Department of Biochemistry, Faculty of Pharmacy, Minia University, El-minia, Egypt. Electronic address: Asmaa_bayoumi@mu.edu.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt; Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia. Electronic address: M.AbdelBakky@qu.edu.sa.Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt. Electronic address: dr.ahmedmmansour@alazhar.edu.eg.Department of Tumor Biology, National Cancer Institute, Cairo University, Cairo, Egypt. Electronic address: marwawka@cu.edu.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; Department of Pharmacology, Faculty of Medicine (Boys), Al-Azhar University, Cairo, Egypt. Electronic address: Ali.aboseif@nub.edu.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafr El Sheikh, Egypt.. Electronic address: shady.allam@pharm.kfs.edu.eg.Department of Pharmacology, National Research Centre, Doki, Giza, Egypt. Electronic address: aa.el-gohary@nrc.sci.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt. Electronic address: salama@alazhar.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32371064

Citation

Elzayat, Mohamed Abdel-Mohsen, et al. "Ameliorative Effect of 2-methoxyestradiol On Radiation-induced Lung Injury." Life Sciences, vol. 255, 2020, p. 117743.
Elzayat MA, Bayoumi AMA, Abdel-Bakky MS, et al. Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury. Life Sci. 2020;255:117743.
Elzayat, M. A., Bayoumi, A. M. A., Abdel-Bakky, M. S., Mansour, A. M., Kamel, M., Abo-Saif, A., Allam, S., Salama, A., & Salama, S. A. (2020). Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury. Life Sciences, 255, 117743. https://doi.org/10.1016/j.lfs.2020.117743
Elzayat MA, et al. Ameliorative Effect of 2-methoxyestradiol On Radiation-induced Lung Injury. Life Sci. 2020 Aug 15;255:117743. PubMed PMID: 32371064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury. AU - Elzayat,Mohamed Abdel-Mohsen, AU - Bayoumi,Asmaa M A, AU - Abdel-Bakky,Mohamed Sadek, AU - Mansour,Ahmed M, AU - Kamel,Marwa, AU - Abo-Saif,Ali, AU - Allam,Shady, AU - Salama,Abeer, AU - Salama,Salama A, Y1 - 2020/05/01/ PY - 2020/01/13/received PY - 2020/04/19/revised PY - 2020/04/28/accepted PY - 2020/5/7/pubmed PY - 2020/6/26/medline PY - 2020/5/7/entrez KW - 2-Methoxyestradiol KW - HIF-1α KW - Macrophages KW - Radiation-induced lung injury KW - TGF-β KW - TNF-α SP - 117743 EP - 117743 JF - Life sciences JO - Life Sci. VL - 255 N2 - AIMS: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms. MAIN METHODS: BALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-β; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot. KEY FINDINGS: The results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-β with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined. SIGNIFICANCE: 2ME2 is a promising radioprotectant with fewer anticipated side effects. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32371064/Ameliorative_effect_of_2-methoxyestradiol_on_radiation-induced_lung_injury L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30491-4 DB - PRIME DP - Unbound Medicine ER -