Role of Nrf2/HO-1 and PI3K/Akt Genes in the Hepatoprotective Effect of Cilostazol
| Autor: | Nagwa M. Zenhom, Heba M. Hafez, Mohamad A Ibrahim, Hend M Abd Elghany, Mervat Z. Mohamed, Marwa Hassan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
NF-E2-Related Factor 2 Phosphodiesterase 3 Thioacetamide Pharmacology Phosphodiesterase 3 Inhibitors 030226 pharmacology & pharmacy Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Protein kinase B PI3K/AKT/mTOR pathway Liver injury business.industry Kinase General Medicine medicine.disease Cilostazol Rats Treatment Outcome chemistry 030220 oncology & carcinogenesis Heme Oxygenase (Decyclizing) Platelet aggregation inhibitor Chemical and Drug Induced Liver Injury business Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Current Clinical Pharmacology. 14:61-67 |
| ISSN: | 1574-8847 |
| DOI: | 10.2174/1574884713666180903163558 |
| Popis: | Background:Cilostazol, a phosphodiesterase 3 inhibitor (PDE3I), is a platelet aggregation inhibitor and vasodilator that is useful for treating intermittent claudication. Experimental studies have shown that cilostazol has potent anti-inflammatory, anti-oxidant effects effects.Objectives:Although the hepatoprotective effect cilostazol has been studied, the molecular mechanisms of such protection, including: the nuclear factor-erythroid 2-related factor 2 (Nrf2) / hemoxygenase (HO-1) and the phosphoinositide 3-kinase (PI3K) /serine/threonine kinase (Akt) pathways are not fully explored, which is the aim of this study.Methods:To achieve the aim of this study, 35 rats were grouped into: control groups, liver injury group (model- non treated: injected with thioacetamide (TAA), 150 mg/kg, i.p.), and two cilostazoltreated groups (treated with cilostazol 10 and 50 mg/kg, p.o.). The rats were treated for 8 days and injected with TAA on the 7th day of the experiment and sacrificed 48 hours after TAA injection.Results:The model group showed evidence of liver injury as indicated by the elevation of liver enzymes and confirmed by histopathological findings. TAA-induced liver injury was accompanied by down-regulation of the cytoprotective pathways: PI3K/Akt and Nrf2/HO-1 mRNAs. Cilostazol administration ameliorated TAA-induced liver injury, where it caused a significant improvement in the activity of liver enzymes as well as in the histopathological changes. Such an effect was associated with a significant increase in the expression of PI3K/Akt and Nrf2/HO-1 mRNAs as detected by Real-time reverse transcription polymerase chain reaction (RT-PCR).Conclusion:Cilostazol protected rats against TAA hepatotoxicity through up-regulation of PI3K/Akt and Nrf2/HO-1 gene expression. |
| Databáze: | OpenAIRE |
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