Local prevention of oxidative stress in the intestinal epithelium of the rat by adhesive liposomes of superoxide dismutase and tempamine.
The purpose of the present study was to investigate whether the local prevention of luminal superoxide-mediated biological damage in the rat jejunal mucosa could be achieved by liposomal superoxide dismutase (SOD) and the SOD mimic tempamine (TMN). Cationic liposomes loaded with either SOD or TMN were perfused in the rat jejunum prior to the induction of oxidative insult. Reactive hydroxyl radicals were generated in situ in a closed circulating intestinal loop of the rat from the reaction between hypoxanthine and xanthine oxidase in the presence of chelated ferrous sulfate. Mucosal activity of lactate dehydrogenase and levels of potassium ions were used to quantify the tissue damage. Intracellular uptake and locality of SOD were examined in HT-29 cells. The intestinal uptake of SOD and TMN was further measured by using rat colon sacs. Entrapment in cationic liposomes was found to significantly enhance the antioxidant effect of SOD and TMN against the induced oxidative damage in the jejunal mucosa, compared with their free forms. The effect was found to be local and was caused by the increased mucosal adhesion of the liposomes. The cationic liposomes also triggered SOD uptake into the HT-29 cell line. It is concluded that the increased residence time of the cationic liposomes of SOD and TMN in the jejunal mucosa resulted in a local effect against oxidative injury. This local protection may be exploited for drug delivery purposes.
Jubeh
Tareq Taha
TT
The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy, P.O. Box 12065, Jerusalem 91120, Israel.
Antler
Sivan
S
Haupt
Susan
S
Barenholz
Yechezkel
Y
Rubinstein
Abraham
A
D000268:Adhesiveness / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D002412:Cations; D003497:Cyclic N-Oxides / Q000378:metabolism / Q000627:therapeutic use*; D005240:Feasibility Studies; D005296:Ferrous Compounds / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D017665:Hydroxyl Radical / Q000633:toxicity; D019271:Hypoxanthine / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007583:Jejunum / Q000201:enzymology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011188:Potassium / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D002412:Cations; D003497:Cyclic N-Oxides; D005296:Ferrous Compounds; D008081:Liposomes; C015527:4-amino-TEMPO; D019271:Hypoxanthine; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D011188:Potassium