The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle.
Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activity. However, its clinical use was restricted to some extent due to its serious toxicity. The possible mechanism for triptolide-induced hepatotoxicity was related to reactive oxygen species (ROS) inducing lipid peroxidation and DNA damage. The development of controlled release delivery strategies could lead to significant advantages in the clinical use of these drugs to decreasing the toxicity. Thus, the present study was focused on the preparation and some characterization of triptolide-loaded solid lipid nanoparticle (SLN) and the measurements of anti-inflammatory activities and the hepatotoxicity of TP-SLN. The carrageenan-induced rat paw edema experiment indicated that the anti-inflammatory activities of TP-SLN were stronger than those of free triptolide. Orally administration of TP-SLN 0.2 or 0.4 mg/kg per day did not cause mortality within the period of observation. In contrast, free triptolide at different doses had caused partial death. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly elevated in the free triptolide-treated group whereas they did not significantly change in TP-SLN-treated mice. The free triptolide increased malondialdehyde (MDA) level and decreased activities of superoxide dismutase (SOD) and total glutathione peroxidase (GSH-Px) in the liver homogenates. However, these phenomena were not found in TP-SLN-treated mice. The results of histopathological evaluation revealed a protective effect of SLN on vacuolation, edema, inflammatory infiltration and necrosis caused by triptolide. Furthermore, TP-SLN did not change Bcl/Bax protein ratio or decrease FasL expression in liver cells. These results suggest that SLN delivery system can enhance the anti-inflammatory activity of triptolide meanwhile has a protective effect against triptolide-induced hepatotoxicity. The toxicity of TP-SLN to other tissues is under investigation.
Mei
Zhinan
Z
Department of Chemistry and Life Science, South-Central University of Nationalities, Wuhan 430074, PR China. meizhinan@163.com
Li
Xiaokuan
X
Wu
Qunrong
Q
Hu
Sheng
S
Yang
Xiangliang
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000633:toxicity*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000633:toxicity; D004224:Diterpenes / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004852:Epoxy Compounds; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000633:toxicity*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide