S Blau1, R Kohen, P Bass, A Rubinstein. 1. The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy, Israel.
Abstract
PURPOSE: 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. CONCLUSION: Cationized catalase and cationized SOD have the potential to be efficient therapeutic tools in the local treatment of colitis.
PURPOSE: 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. CONCLUSION: Cationized catalase and cationized SOD have the potential to be efficient therapeutic tools in the local treatment of colitis.
Authors: J V Hawkins; E L Emmel; J J Feuer; M A Nedelman; C J Harvey; H J Klein; H Rozmiarek; A R Kennedy; G R Lichtenstein; P C Billings Journal: Dig Dis Sci Date: 1997-09 Impact factor: 3.199
Authors: J Schalkwijk; W B van den Berg; L B van de Putte; L A Joosten; L van den Bersselaar Journal: J Clin Invest Date: 1985-07 Impact factor: 14.808