Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue
- PDF / 1,134,267 Bytes
- 5 Pages / 595.276 x 790.866 pts Page_size
- 67 Downloads / 178 Views
MOLECULAR TOXICOLOGY
Effect of common medications on the expression of SARS‑CoV‑2 entry receptors in liver tissue Narjes Saheb Sharif‑Askari1 · Fatemeh Saheb Sharif‑Askari1 · Bushra Mdkhana1 · Saba Al Heialy2,8 · Elaref Ratemi3 · Malak Alghamdi4 · Salah Abusnana5,6 · Tarek Kashour7 · Qutayba Hamid1,5,8 · Rabih Halwani1,5,9 Received: 26 April 2020 / Accepted: 12 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Besides lung drastic involvement, SARS-CoV-2 severely affected other systems including liver. Emerging epidemiological studies brought the attentions towards liver injury and impairment as a potential outcome of COVID19. Angiotensinconverting enzyme 2 (ACE2) and Transmembrane serine protease (TMPRSS2) are the main cell entry receptors of SARSCoV-2. We have tested the ability of medications to regulate expression of SARS-CoV-2 receptors. Understanding that may reflect how such medications may affect the level of infectivity and permissibility of the liver following COVID-19. Using transcriptomic datasets, Toxicogenomic Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) and GSE30351, we have tested the ability of ninety common medications to regulate COVID-19 receptors expression in human primary hepatocytes. Most medications displayed a dose-dependent change in expression of receptors which could hint at a potentially more pronounced change with chronic use. The expression level of TMPRSS2 was increased noticeably with a number of medications such as metformin. Within the analgesics, acetaminophen revealed a dose-dependent reduction in expression of ACE2, while non-steroidal anti-inflammatory drugs had mixed effect on receptors expression. To confirm the observed effects on primary human hepatocytes, rat hepatocyte treatments data was obtained from DrugMatrix toxicogenomic database (GSE57805), which showed a similar ACE2 and TMPRSS2 expression pattern. Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2. More research is needed to determine the effect of different medications on COVID-19 receptors. Keywords ACE2 · TMPRSS2 · SARS-CoV-2 · COVID-19 · Liver · Medications · Metformin · Acetaminophen · Nsaids · Hepatocyte
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-020-02869-1) contains supplementary material, which is available to authorized users. 5
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
6
Diabetes and Endocrinology Department, University Hospital Sharjah, Sharjah, United Arab Emirates
7
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
Department of Cardiology, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia
8
Department of Chemical and Process Engineering Technology, Jubail Industrial College, Jubail Indu
Data Loading...
