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Role of Nrf2/HO-1 and PI3K/Akt Genes in the Hepatoprotective Effect of Cilostazol

[ Vol. 14 , Issue. 1 ]

Author(s):

Marwa Hassan*, Mohamad A. Ibrahim, Heba M. Hafez, Mervat Z. Mohamed, Nagwa M. Zenhom and Hend M. Abd Elghany Pages 61-67 (7)

Abstract:


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.

Keywords:

PI3K/Akt, Nrf2/HO-1, thioacetamide, hepatotoxicity, cilostazol, angiogenesis.

Affiliation:

Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia

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