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Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the
Fatima Khirfan1, Yazun Jarrar1, Tariq Al-Qirim1
1Department of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11731, Jordan.
Abstract:
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, ACE2, TMPRSS2, and Ctsl genes, in addition to the arachidonic-acid-metabolizing cyp450, cox, and alox genes, were analyzed using real-time PCR. Paracetamol increased the expressions of TMPRSS2 and Ctsl genes by 8.5 and 5.6 folds, respectively, while ibuprofen and diclofenac significantly decreased the expression of the ACE2 gene by more than 2.5 folds. In addition, all tested drugs downregulated (p < 0.05) cox2 gene expression, and paracetamol reduced the mRNA levels of cyp4a12 and 2j5. 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.
Insights
Common analgesics like paracetamol and ibuprofen alter key gene expressions in mouse lungs. These drugs affect genes involved in SARS-CoV-2 entry and inflammation, potentially impacting respiratory viral infection management.
Area of Science:
- Pharmacology
- Molecular Biology
- Virology
Background:
- Paracetamol and NSAIDs are frequently used for respiratory viral infections.
- The impact of these analgesics on viral entry and inflammatory gene expression remains incompletely understood.
Purpose of the Study:
- To investigate the effects of paracetamol, ibuprofen, and diclofenac on SARS-CoV-2 entry and arachidonic acid metabolism genes in mouse lungs.
- To correlate molecular changes with potential pathohistological alterations.
Main Methods:
- Balb/c mice were administered vehicle, paracetamol, ibuprofen, or diclofenac for 14 days.
- Real-time PCR was used to analyze the mRNA expression of SARS-CoV-2 entry genes (ACE2, TMPRSS2, Ctsl) and arachidonic acid-metabolizing genes (cyp450, cox, alox).
Main Results:
- Paracetamol upregulated TMPRSS2 and Ctsl expression.
- Ibuprofen and diclofenac downregulated ACE2 expression.
- All tested drugs downregulated cox2, and paracetamol affected cyp4a12 and 2j5 mRNA levels.
- Ibuprofen and diclofenac induced inflammatory cell infiltration and airway wall thickening.
Conclusions:
- Analgesics including paracetamol, ibuprofen, and diclofenac modulate the expression of genes critical for SARS-CoV-2 entry and arachidonic acid metabolism in the lungs.
- These molecular alterations may have implications for the use of these common medications during respiratory viral infections.
