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Communication

Old Drug, New Trick: Tilorone, a Broad-Spectrum Antiviral Drug as a Potential Anti-Fibrotic Therapeutic for the Diseased Heart

1
Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
2
Department of Cardiology, Alfred Hospital, Melbourne, VIC 3004, Australia
3
Department of Medicine, Monash University, Clayton, VIC 3800, Australia
4
Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia
5
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Disease in Central Asia, Clinical Medical Research Institute of Xinjiang Medical University, Urumqi 830054, China
6
Centre for Muscle Research, Department of Physiology, University of Melbourne, Parkville, VIC 3010, Australia
7
Department of Diabetes, Central Clinical School, Monash University, Clayton, VIC 3800, Australia
8
Department of Physiology, Monash University, Clayton, VIC 3800, Australia
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Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia
10
Department of Paediatrics, University of Melbourne, VIC 3010, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Maria Emília de Sousa
Pharmaceuticals 2021, 14(3), 263; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030263
Received: 10 February 2021 / Revised: 9 March 2021 / Accepted: 10 March 2021 / Published: 15 March 2021
(This article belongs to the Collection Old Pharmaceuticals with New Applications)
Cardiac fibrosis is associated with most forms of cardiovascular disease. No reliable therapies targeting cardiac fibrosis are available, thus identifying novel drugs that can resolve or prevent fibrosis is needed. Tilorone, an antiviral agent, can prevent fibrosis in a mouse model of lung disease. We investigated the anti-fibrotic effects of tilorone in human cardiac fibroblasts in vitro by performing a radioisotopic assay for [3H]-proline incorporation as a proxy for collagen synthesis. Exploratory studies in human cardiac fibroblasts treated with tilorone (10 µM) showed a significant reduction in transforming growth factor-β induced collagen synthesis compared to untreated fibroblasts. To determine if this finding could be recapitulated in vivo, mice with established pathological remodelling due to four weeks of transverse aortic constriction (TAC) were administered tilorone (50 mg/kg, i.p) or saline every third day for eight weeks. Treatment with tilorone was associated with attenuation of fibrosis (assessed by Masson’s trichrome stain), a favourable cardiac gene expression profile and no further deterioration of cardiac systolic function determined by echocardiography compared to saline treated TAC mice. These data demonstrate that tilorone has anti-fibrotic actions in human cardiac fibroblasts and the adult mouse heart, and represents a potential novel therapy to treat fibrosis associated with heart failure. View Full-Text
Keywords: heart failure; fibrosis; tilorone; pressure overload; fibroblast; treatment; therapy heart failure; fibrosis; tilorone; pressure overload; fibroblast; treatment; therapy
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MDPI and ACS Style

Horlock, D.; Kaye, D.M.; Winbanks, C.E.; Gao, X.-M.; Kiriazis, H.; Donner, D.G.; Gregorevic, P.; McMullen, J.R.; Bernardo, B.C. Old Drug, New Trick: Tilorone, a Broad-Spectrum Antiviral Drug as a Potential Anti-Fibrotic Therapeutic for the Diseased Heart. Pharmaceuticals 2021, 14, 263. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030263

AMA Style

Horlock D, Kaye DM, Winbanks CE, Gao X-M, Kiriazis H, Donner DG, Gregorevic P, McMullen JR, Bernardo BC. Old Drug, New Trick: Tilorone, a Broad-Spectrum Antiviral Drug as a Potential Anti-Fibrotic Therapeutic for the Diseased Heart. Pharmaceuticals. 2021; 14(3):263. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030263

Chicago/Turabian Style

Horlock, Duncan, David M. Kaye, Catherine E. Winbanks, Xiao-Ming Gao, Helen Kiriazis, Daniel G. Donner, Paul Gregorevic, Julie R. McMullen, and Bianca C. Bernardo 2021. "Old Drug, New Trick: Tilorone, a Broad-Spectrum Antiviral Drug as a Potential Anti-Fibrotic Therapeutic for the Diseased Heart" Pharmaceuticals 14, no. 3: 263. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030263

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