The effect of local attachment of cationized antioxidant enzymes on experimental colitis in the rat.
OBJECTIVE
To investigate the possibility of local treatment of colitis with the adhesive antioxidant enzymes catalase and superoxide dismutase (SOD).


METHODS
The net electric charge of the enzymes' surfaces was modified from negative to positive, to cause their adherence to the colon epithelium. The effects of this local administration were assessed in inflamed rat colon. Inflammation severity (colitis) was assessed by measuring colonic tissue myeloperoxidase (MPO) activity, amounts of tumour necrosis factor alpha (TNFalpha) and concentrations of reduced glutathione (GSH). The measurements were carried out in two types of protocols: preventive (pre-colitis induction) and treatment (post-colitis induction). In addition, the efficacy of treatment with the cationized enzymes was compared to 5-aminosalicylic acid (5-ASA) and betamethasone with similar administration routes.


RESULTS
The two cationized antioxidant enzymes were found to be efficient in both prevention and treatment of experimental colitis. The two cationized enzymes caused a significant reduction in MPO activity. A reduction in TNFalpha concentration was noted only after the treatment protocol. No correlation was found between inflammation severity and tissue levels of GSH. In most cases the cationized enzymes were more effective than 5-ASA and betamethasone.


CONCLUSIONS
Cationized catalase and cationized SOD have the potential to be efficient therapeutic tools in the local treatment of colitis.
Blau
S
S
The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy, Israel.
Kohen
R
R
Bass
P
P
Rubinstein
A
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001623:Betamethasone / Q000494:pharmacology / Q000627:therapeutic use; D002374:Catalase / Q000494:pharmacology* / Q000627:therapeutic use; D002412:Cations / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000494:pharmacology / Q000627:therapeutic use; D009195:Peroxidase / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002412:Cations; D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D019804:Mesalamine; D001623:Betamethasone; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione