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.