Anti-inflammatory effect of recombinant human superoxide dismutase in rats and mice and its mechanism.
OBJECTIVE
To investigate the anti-inflammatory effects and mechanism of recombinant human superoxide dismutase (rhSOD).


METHODS
Inflammation models such as croton oil-induced ear swelling and carrageenan-induced hind paw edema in mice and rats were prepared. The nitric oxide synthase (NOS ) activity was measured by NADPH-diaphoras stain assay, N-acetyl-beta-D-glucosaminidase (beta-NAG) activity by spectrophotography, malondialdehyde (MDA) content by thiobarbituric acid (TBA) fluorescence technique, and interleukin-1beta (IL -1beta), tumor necrosis factor alpha (TNF alpha), and IL-8 content by radioimmunoassay (RIA).


RESULTS
rhSOD 20-80 mg/kg ip, 40-80 mg/kg im, and 80 mg/kg ip significantly inhibited carrageenan-induced paw edema in rats, croton oil-induced ear swelling in mice, and carrageenan-induced hind paw edema in mice, respectively. In the rat arthritis induced by carrageenan, rhSOD 40 mg/kg reduced MDA content in inflamed paws, inhibited NOS activity, and lowered the content of IL-1beta and TNFalpha in exudate significantly. The inhibitory effect of rhSOD 40 mg/kg ip on IL-1beta production was more evident than that of dexamethasone 2 mg/kg ip. Also rhSOD obviously inhibited neutrophil infiltration; However, rhSOD had no effect on beta-NAG activity in exudate.


CONCLUSIONS
rhSOD has anti-inflammatory effect on experimental inflammation in rats and mice, and its mechanisms are relevant to oxygen free radical scavenging, anti-lipid peroxidation, inhibition of neutrophil infiltration, and formation of inflammatory cytokines.
Zhang
Yi
Y
National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China. bjzhangyi@163.net.
Wang
Jun-Zhi
JZ
Wu
Yong-Jie
YJ
Li
Wen-Guang
WG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002351:Carrageenan; D003436:Croton Oil; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003436:Croton Oil; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase