title: Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats.
abstract: Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30 mg/kg) and TWHF group (120, 60, 30 mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60 mg/kg (p<0.05) and PG levels in serum (p<0.05); the levels of ALT, AST, ALP, GGT in serum and MDA, XOD, GSH-PX in liver were not significantly elevated. Histopathology observation found that free TWHF caused more serious damage to the liver than TWHF-SLN. These results revealed that SLN delivery system can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF-induced hepatotoxicity.
authors.affiliation: Jiangsu Center for Drug Screening Laboratory, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, Jiangsu Province 210009, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.forename: Zhen-zhou
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
authors.forename: Shu-yu
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004487:Edema / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D008055:Lipids; D010936:Plant Extracts