Augmented inhibitory effect of superoxide dismutase on superoxide anion release from macrophages by chemical modification with polysaccharide and attenuation effects on radiation-induced inflammatory cytokine expression in vitro.
To improve the ability of superoxide dismutase (SOD) to suppress reactive oxygen species (ROS)-mediated injury, chemically modified derivatives of SOD with N,N,N-trimethyl chitosan chloride (TMC) and heparin, cationized SOD (TMC-SOD), and anionized SOD (heparin-SOD) were designed and prepared. In this study, the inhibitory effect of TMC-SOD and heparin-SOD on superoxide anion release from macrophages was studied in vitro. Both TMC-SOD and heparin-SOD exhibited excellent inhibitory effects on superoxide anion release from macrophages, and the effects of TMC-SOD surpassed those of native SOD and heparin-SOD. The effects of TMC-SOD and heparin-SOD on inflammatory cytokine expression in vitro were also evaluated. The results showed that both TMC-SOD and heparin-SOD could significantly lower the levels of transforming growth factor-beta1 (TGF-beta1) and interleukine-1beta (IL-1beta) expressed by irradiated 3T3 fibroblasts. These results demonstrated that cationic polysaccharide or anionic polysaccharide SOD derivatives might be useful in the prevention and treatment of ROS-mediated inflammatory diseases. This study also demonstrated that chemical modification of SOD, especially cationization, greatly enhanced SOD's intracellular delivery and, consequently, produced a significant protective effect against ROS-mediated injury.
Liu
Jinfeng
J
Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, Jinan, China.
Teng
Li
L
Liu
Chunhui
C
Hu
Likuan
L
Wang
Yonggang
Y
Liu
Hong
H
Wang
Fengshan
F
D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis*; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D004337:Drug Carriers; D053583:Interleukin-1beta; C118071:N-trimethyl chitosan chloride; D053773:Transforming Growth Factor beta1; D013481:Superoxides; D006493:Heparin; D048271:Chitosan; D013482:Superoxide Dismutase