Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs
Paracetamol and nonsteroidal anti-inflammatory drugs are widely used in the management of respiratory viral infections. This study aimed to determine the effects of the most commonly used analgesics (paracetamol, ibuprofen, and diclofenac) on the mRNA expression of severe acute respiratory syndrome...
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MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/696 |
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| author | Fatima Khirfan Yazun Jarrar Tariq Al-Qirim Khang Wen Goh Qais Jarrar Chrismawan Ardianto Mohammad Awad Hamzeh J. Al-Ameer Wajdy Al-Awaida Said Moshawih Long Chiau Ming |
| author_facet | Fatima Khirfan Yazun Jarrar Tariq Al-Qirim Khang Wen Goh Qais Jarrar Chrismawan Ardianto Mohammad Awad Hamzeh J. Al-Ameer Wajdy Al-Awaida Said Moshawih Long Chiau Ming |
| author_sort | Fatima Khirfan |
| collection | DOAJ |
| description | Paracetamol and nonsteroidal anti-inflammatory drugs are widely used in the management of respiratory viral infections. This study aimed to determine the effects of the most commonly used analgesics (paracetamol, ibuprofen, and diclofenac) on the mRNA expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and arachidonic-acid-metabolizing genes in mouse lungs. A total of twenty eight Balb/c mice were divided into four groups and treated separately with vehicle, paracetamol, ibuprofen, and diclofenac in clinically equivalent doses for 14 days. Then, the expressions of SARS-CoV-2 entry, <i>ACE2</i>, <i>TMPRSS2</i>, and <i>Ctsl</i> genes, in addition to the arachidonic-acid-metabolizing <i>cyp450</i>, <i>cox</i>, and <i>alox</i> genes, were analyzed using real-time PCR. Paracetamol increased the expressions of <i>TMPRSS2</i> and <i>Ctsl</i> genes by 8.5 and 5.6 folds, respectively, while ibuprofen and diclofenac significantly decreased the expression of the <i>ACE2</i> gene by more than 2.5 folds. In addition, all tested drugs downregulated (<i>p</i> < 0.05) <i>cox2</i> gene expression, and paracetamol reduced the mRNA levels of <i>cyp4a12</i> and <i>2j5</i>. These molecular alterations in diclofenac and ibuprofen were associated with pathohistological alterations, where both analgesics induced the infiltration of inflammatory cells and airway wall thickening. It is concluded that analgesics such as paracetamol, ibuprofen, and diclofenac alter the expression of SARS-CoV-2 entry and arachidonic-acid-metabolizing genes in mouse lungs. |
| first_indexed | 2024-03-09T22:47:19Z |
| format | Article |
| id | doaj.art-55df72e9f2304e22aae7f54bfc496e59 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:19Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-55df72e9f2304e22aae7f54bfc496e592023-11-23T18:27:10ZengMDPI AGPharmaceuticals1424-82472022-06-0115669610.3390/ph15060696Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse LungsFatima Khirfan0Yazun Jarrar1Tariq Al-Qirim2Khang Wen Goh3Qais Jarrar4Chrismawan Ardianto5Mohammad Awad6Hamzeh J. Al-Ameer7Wajdy Al-Awaida8Said Moshawih9Long Chiau Ming10Department of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11731, JordanDepartment of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11731, JordanDepartment of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11731, JordanFaculty of Data Science and Information Technology, INTI International University, Nilai 71800, MalaysiaDepartment of Applied Pharmaceutical Sciences, Faculty of Pharmacy, Al-Isra University, Amman 11622, JordanDepartment of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, IndonesiaDepartment of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11731, JordanDepartment of Biology and Biotechnology, American University of Madaba, Madaba 17110, JordanDepartment of Biology and Biotechnology, American University of Madaba, Madaba 17110, JordanPAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong BE1410, Brunei DarussalamDepartment of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, IndonesiaParacetamol and nonsteroidal anti-inflammatory drugs are widely used in the management of respiratory viral infections. This study aimed to determine the effects of the most commonly used analgesics (paracetamol, ibuprofen, and diclofenac) on the mRNA expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and arachidonic-acid-metabolizing genes in mouse lungs. A total of twenty eight Balb/c mice were divided into four groups and treated separately with vehicle, paracetamol, ibuprofen, and diclofenac in clinically equivalent doses for 14 days. Then, the expressions of SARS-CoV-2 entry, <i>ACE2</i>, <i>TMPRSS2</i>, and <i>Ctsl</i> genes, in addition to the arachidonic-acid-metabolizing <i>cyp450</i>, <i>cox</i>, and <i>alox</i> genes, were analyzed using real-time PCR. Paracetamol increased the expressions of <i>TMPRSS2</i> and <i>Ctsl</i> genes by 8.5 and 5.6 folds, respectively, while ibuprofen and diclofenac significantly decreased the expression of the <i>ACE2</i> gene by more than 2.5 folds. In addition, all tested drugs downregulated (<i>p</i> < 0.05) <i>cox2</i> gene expression, and paracetamol reduced the mRNA levels of <i>cyp4a12</i> and <i>2j5</i>. These molecular alterations in diclofenac and ibuprofen were associated with pathohistological alterations, where both analgesics induced the infiltration of inflammatory cells and airway wall thickening. It is concluded that analgesics such as paracetamol, ibuprofen, and diclofenac alter the expression of SARS-CoV-2 entry and arachidonic-acid-metabolizing genes in mouse lungs.https://www.mdpi.com/1424-8247/15/6/696COVID-19lung diseasechronic respiratory diseaseacute respiratory distress syndromegene expression |
| spellingShingle | Fatima Khirfan Yazun Jarrar Tariq Al-Qirim Khang Wen Goh Qais Jarrar Chrismawan Ardianto Mohammad Awad Hamzeh J. Al-Ameer Wajdy Al-Awaida Said Moshawih Long Chiau Ming Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs Pharmaceuticals COVID-19 lung disease chronic respiratory disease acute respiratory distress syndrome gene expression |
| title | Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs |
| title_full | Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs |
| title_fullStr | Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs |
| title_full_unstemmed | Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs |
| title_short | Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs |
| title_sort | analgesics induce alterations in the expression of sars cov 2 entry and arachidonic acid metabolizing genes in the mouse lungs |
| topic | COVID-19 lung disease chronic respiratory disease acute respiratory distress syndrome gene expression |
| url | https://www.mdpi.com/1424-8247/15/6/696 |
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