Single intravenous injection of plasmid DNA encoding human paraoxonase-1 inhibits hyperlipidemia in rats.
Paraoxonase-1 (PON1, EC 3.1.8.1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme, and its activity correlates negatively with the level of plasma low-density lipoprotein cholesterol (LDL-C) and triglyceridemia (TG). In this study, we examined the therapeutic effect of plasmid DNA containing the human PON1 gene (pcDNA/PON1) in hyperlipidemic model rats. The rats were fed a high-fat and high-cholesterol diet for 25 days to produce a hyperlipidemic animal model. Single intravenous injection of pcDNA/PON1 into model rats prevented dyslipidemia and hepatic lipid accumulation. The mechanisms of pcDNA/PON1 in treating hyperlipidemia were associated with increases of serum antioxidant PON1 and SOD activities, and with reduction of the levels of total cholesterol (TC), LDL-C and TG. The results suggest the potential therapeutic effect of pcDNA/PON1 on hyperlipidemia.
Fu
Ai Ling
AL
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. A.L.Fu@hotmail.com
Wu
Shao Ping
SP
D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D004247:DNA / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006949:Hyperlipidemias / Q000628:therapy*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D010957:Plasmids / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D014280:Triglycerides / Q000097:blood
D008078:Cholesterol, LDL; D014280:Triglycerides; D004247:DNA; D013482:Superoxide Dismutase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human