Cilostazol attenuates indices of liver damage induced by thioacetamide in albino rats through regulating inflammatory cytokines and apoptotic biomarkers.

Even though cilostazol was assessed before in several models of atherosclerosis, so far its full systematic effect as a natural anti-inflammatory and anti-apoptotic mediator in the protection of liver damage and complication has not been fully clarified, which is the target of this study. For that purpose, we examined the protective effect of cilostazol (10 and 5mg/kg, p.o. b.wt.) in an acute hepatic injury model by orally injecting it for 3 weeks prior to a single dose of TAA (300mg/kg, i.p) injection. Ursodeoxycholic acid was used as a standard drug (50mg/kg, p.o. b.wt.). After injection of thioacetamide by 48hr, rats were sacrificed. On the serum biochemical level, cilostazol ameliorated the thioacetamide consequence, where it presented a significant enhancement in the liver enzymes activities [Aspartate aminotransferase (AST) & Alanine aminotransferase (ALT)]. On the other hand, at the tissue level (Liver), it revealed a significant improvement in pro-inflammatory cytokines [Tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), Nuclear factor kappa B (NF-κB), NF-κB (P65/P50 nucleus translocation), caspase-3, cleaved caspase-3 & C-reactive protein (CRP)], redox level [Reduced glutathione (GSH) & Malondialdehyde (MDA)], histopathological findings, Reverse transcription polymerase chain reaction (RT-PCR) analysis (expression of TNF-α and NF-κB mRNA levels), and immunohistochemical reaction (caspase-3 & TNF-α). Obviously, the high dose of cilostazol (10mg/kg, p.o. b.wt.) displayed a more pronounced effect than its lower one and nearly equal to ursodeoxycholic acid in the most of the parameters. These results give a new awareness into the hopeful molecular mechanisms by which cilostazol attenuates several factors participated in the progression of liver damage.