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-beta 1 (TGF-beta 1) and interleukine-1 beta (IL-1 beta) 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.