Comparative evaluation of the protective potentials of human paraoxonase 1 and 3 against CCl4-induced liver injury

We previously reported that electroporation mediated hPON1 or hPON3 gene delivery could protect against CCl4-induced liver injury. However, substantial evidence supported that the in vivo physiological functions of hPON1 and hPON3 were distinct. To compare the protective efficacies of hPON1 and hPON3 against liver injury, recombinant adenovirus AdPON1 and AdPON3, which were capable of expressing hPON1 and hPON3 respectively, were intravenously injected into mice before they were given CCl4. Adenovirus mediated expression of hPON1 and hPON3 were demonstrated by elevated serum esterase activity, hepatic lactonase activity, and hPON1/hPON3 mRNA expression in liver. Serum transaminase assay, histological observation and TUNEL analysis revealed that the extent of liver injury and hepatocyte apoptosis in AdPON1 or AdPON3 treated mice was significantly ameliorated in comparison with control. Meanwhile, overexpression of hPON1 and hPON3 reduced the hepatic oxidative stress and strengthen the total antioxidant capabilities in liver through affecting the hepatic malondialdehyde (MDA), glutathione (GSH) and total antioxidant capability (T-AOC) levels, regardless of the exposure to CCl4 or corn oil. Administration of AdPON1 or AdPON3 also suppressed inflammatory response by decreasing TNF-alpha and IL-1 beta levels in CCl4 mice. In this study, hPON1 exhibited a slightly higher efficacy than hPON3 in alleviating liver injury, but the difference between them were not significant. (C) 2010 Elsevier Ireland Ltd. All rights reserved.