Effects of nonsteroidal anti-inflammatory drugs on the expression of arachidonic acid-metabolizing Cyp450 genes in mouse hearts, kidneys and livers
Autor: | Yazun Jarrar, Mohammad Abu-Shalhoob, Qais Jarrar, Abdulqader Fadhil Abed |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Mefenamic acid Physiology medicine.drug_class 030204 cardiovascular system & hematology Pharmacology Kidney Biochemistry Anti-inflammatory Gene Expression Regulation Enzymologic 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Diclofenac Cytochrome P-450 Enzyme System Gene expression medicine Animals Cardiotoxicity Arachidonic Acid business.industry Myocardium Anti-Inflammatory Agents Non-Steroidal Heart Cell Biology Meloxicam 030104 developmental biology medicine.anatomical_structure chemistry Liver Arachidonic acid business medicine.drug |
Zdroj: | Prostaglandinsother lipid mediators. 141 |
ISSN: | 1098-8823 |
Popis: | Arachidonic acid (ARA) metabolites are involved in cardiovascular diseases and drug-induced cardiotoxicity. The present study aimed to investigate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the gene expression of ARA-metabolizing cyp450 genes in the hearts, kidneys and livers of experimental mice. Thirty five Balb/c mice were divided into 5 groups, and each group contained 7 mice. Then, the groups were administered different NSAIDs, diclofenac mefenamic acid, ibuprofen, or meloxicam, for 14 days in doses equivalent to those used in human treatment. Subsequently, liver, kidney and heart samples were isolated for analysis of the expression of ARA-metabolizing cyp450 genes using real-time polymerase chain reaction. In addition, the histological alterations induced by mefenamic acid were examined. It was found that 20-HETE synthesizing gene cyp4a12 was upregulated (2.2 fold) in the hearts of NSAID-treated mice, which was associated with the 2-fold downregulation of the cardio-protective biomarker GATA4 gene and the induction of cox2 expression (p value0.05). In the kidneys, the expression of cyp4a12 was significantly reduced (p value0.05) while cyp2c29 expression was upregulated by more than 2 fold. In the liver, all NSAIDs except diclofenac significantly decreased the expression of all genes tested (p value0.05) and were associated with abnormal accumulation of fat in the liver. Furthermore, these molecular findings were in parallel to histological alterations induced in the liver, kidney, and heart after mefenamic acid administration. This study concluded that NSAIDs altered the expression of ARA-metabolizing cyp450 genes and induced histological alterations that may influence the function of the vital organs. |
Databáze: | OpenAIRE |
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