Anti-inflammatory effect of recombinant human superoxide dismutase in rats and mice and its mechanism.
Abstract
AIM: 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.
CONCLUSION: 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.
Keywords:
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.
CONCLUSION: 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.