Local Prevention of Oxidative Stress in the Intestinal Epithelium of the Rat by Adhesive Liposomes of Superoxide Dismutase and Tempamine

Abstract

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.

The protective role of silymarin against methotrexate-induced gastrointestinal injury

“…It has been reported that antioxidants play an important role in the regulation of the gastrointestinal tract. Glutathione and glutathione related enzymes which might have a protective role on the inflammatory diseases of GIS have been reported in experimental studies (Jubeh et al, 2005;Siegers et al, 1988). In the present study, blood GSH level in MTX+SLY group was significantly increased compared to MTX group.…”

The protective role of silymarin against methotrexate-induced gastrointestinal injury

“…It has been reported that antioxidants play an important role in the regulation of the gastrointestinal tract. Glutathione and glutathione related enzymes which might have a protective role on the inflammatory diseases of GIS have been reported in experimental studies (Jubeh et al, 2005;Siegers et al, 1988). In the present study, blood GSH level in MTX+SLY group was significantly increased compared to MTX group.…”

Dietary Antioxidants: From Micronutrients and Phytochemicals to Enzymes - Preventive Effects on Early Atherosclerosis and Obesity

“…Even though involved mechanisms remain unclear, it is known that SOD can be absorbed despite its high MW (∼35 kDa). This was shown in the liver of rats after intravenous administration of SOD conjugated with colloidal gold (Dini et al, 1996) and more recently in HT-29 cells using liposomal SOD and the SOD mimic tempamine (Jubeh et al, 2005).…”

Effect of Mirtazapine on Gastric Oxidative Stress and DNA Injury Created With Methotrexate in Rats

“…In present study, significant elevation in quantity of MDA was seen in the gastric tissue of the control group administered MTX. In another study, significant elevation in quantity of MDA, reduction in quantity of gluthation in bowel injury created with MTX were reported 17 . Again in another study, MDA quantity in the injured gastric tissue was found to be high in proportion to the non-injured tissue 18 .…”

The protective role of silymarin against methotrexate-induced gastrointestinal injury

“…It has been reported that antioxidants play an important role in the regulation of the gastrointestinal tract. Glutathione and glutathione related enzymes which might have a protective role on the inflammatory diseases of GIS have been reported in experimental studies (Jubeh et al, 2005;Siegers et al, 1988). In the present study, blood GSH level in MTX+SLY group was significantly increased compared to MTX group.…”

Dietary Antioxidants: From Micronutrients and Phytochemicals to Enzymes - Preventive Effects on Early Atherosclerosis and Obesity

“…Even though involved mechanisms remain unclear, it is known that SOD can be absorbed despite its high MW (∼35 kDa). This was shown in the liver of rats after intravenous administration of SOD conjugated with colloidal gold (Dini et al, 1996) and more recently in HT-29 cells using liposomal SOD and the SOD mimic tempamine (Jubeh et al, 2005).…”

Effect of Mirtazapine on Gastric Oxidative Stress and DNA Injury Created With Methotrexate in Rats

“…In present study, significant elevation in quantity of MDA was seen in the gastric tissue of the control group administered MTX. In another study, significant elevation in quantity of MDA, reduction in quantity of gluthation in bowel injury created with MTX were reported 17 . Again in another study, MDA quantity in the injured gastric tissue was found to be high in proportion to the non-injured tissue 18 .…”

The protective role of silymarin against methotrexate-induced gastrointestinal injury

“…It has been reported that antioxidants play an important role in the regulation of the gastrointestinal tract. Glutathione and glutathione related enzymes which might have a protective role on the inflammatory diseases of GIS have been reported in experimental studies (Jubeh et al, 2005;Siegers et al, 1988). In the present study, blood GSH level in MTX+SLY group was significantly increased compared to MTX group.…”

Dietary Antioxidants: From Micronutrients and Phytochemicals to Enzymes - Preventive Effects on Early Atherosclerosis and Obesity

“…Even though involved mechanisms remain unclear, it is known that SOD can be absorbed despite its high MW (∼35 kDa). This was shown in the liver of rats after intravenous administration of SOD conjugated with colloidal gold (Dini et al, 1996) and more recently in HT-29 cells using liposomal SOD and the SOD mimic tempamine (Jubeh et al, 2005).…”

Effect of Mirtazapine on Gastric Oxidative Stress and DNA Injury Created With Methotrexate in Rats

“…In present study, significant elevation in quantity of MDA was seen in the gastric tissue of the control group administered MTX. In another study, significant elevation in quantity of MDA, reduction in quantity of gluthation in bowel injury created with MTX were reported 17 . Again in another study, MDA quantity in the injured gastric tissue was found to be high in proportion to the non-injured tissue 18 .…”