Protective effects of chlorogenic acid against ischemia/reperfusion injury in rat liver: molecular evidence of its antioxidant and anti-inflammatory properties.

Hepatic ischemia and reperfusion injury (I/R) is accompanied by excessive reactive oxygen species and resultant sterile inflammation. Chlorogenic acid (CGA), one of the most abundant polyphenols in the human diet, has been shown to exert potent anti-inflammatory, antibacterial and antioxidant activities. Thus, the purpose of the present study was to investigate protective effects of CGA and its molecular mechanisms against hepatic I/R injury. Rats were subjected to 60 min of partial hepatic ischemia followed by 5 h of reperfusion. CGA (2.5, 5 and 10 mg/kg, ip) was administered twice: 10 min prior to ischemia and 10 min before reperfusion. CGA treatment resulted in marked improvement of hepatic function and histology, and suppressed oxidative stress, as indicated by hepatic lipid peroxidation and glutathione level. Levels of serum tumor necrosis factor-α, inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions were up-regulated after I/R; these effects were attenuated by CGA. Immunoblot results showed that CGA reduced I/R-induced toll-like receptor 4 overexpression, nuclear translocation of nuclear factor kappa B and interferon regulatory factor-1, high-mobility group box-1 release into extracellular milieu, and enhanced heme oxygenase-1 expression and nuclear translocation of nuclear factor erythroid 2-related factor 2. Our results suggest that CGA alleviates I/R-induced liver injury and that this protection is likely due to inhibition of inflammatory response and enhancement of antioxidant defense systems. Therefore, CGA might have potential as an agent for use in clinical treatment of hepatic I/R injury.