Assessment of a human recombinant manganese superoxide dismutase in models of inflammation.
We evaluated a novel human recombinant preparation of manganese superoxide dismutase (MnSOD) for anti-inflammatory and anti-oxidant activity compared with a copper zinc (CuZn) SOD preparation. The results showed that administration of MnSOD (50, 100 and 200 micrograms kg-1) in the Freund's Complete Adjuvant (FCA) mediated paw oedema model suppressed the inflammation at 4 hours by 43, 25 and 43% (P < 0.001, P < 0.01 and P < 0.001 at respective doses). However, 24 hours post-challenge, MnSOD (50 and 100 micrograms kg-1), suppressed the inflammation by 19% (P < 0.001). In contrast, Mn SOD at higher doses (400-800 micrograms kg-1; 2 mgkg-1) exacerbated the inflammatory response at 4 hours. This pro-inflammatory response declined progressively by 24 hours. Furthermore, CuZn SOD produced no significant effects on the inflammatory response. In the carrageenan-induced synovitis model, Mn SOD (25 and 50 micrograms; intra-articular administration) exacerbated the inflammation at 48 hours. In contrast, Mn SOD at 5 micrograms produced a significant suppression (44%, P < 0.05) in knee joint swelling at 24 hours. The CuZn SOD preparation produced marked pro-inflammatory effects in the joints whilst it lacked activity in the FCA-mediated paw oedema model. These findings support a therapeutic potential of MnSOD in inflammatory disorders, however the compound has a complex pharmaco-dynamic profile.
Dowling
E J
EJ
Bone and Joint Research Unit, London Hospital Medical College, England.
Chander
C L
CL
Claxson
A W
AW
Lillie
C
C
Blake
D R
DR
D000818:Animals; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000276:immunology; D005609:Free Radicals; D005620:Freund's Adjuvant; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008345:Manganese; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use*; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy
D005609:Free Radicals; D011994:Recombinant Proteins; D008345:Manganese; D002351:Carrageenan; D005620:Freund's Adjuvant; D013482:Superoxide Dismutase