Multi-Antioxidant Supplementation Does Not Prevent an Increase in Gut Permeability after Lower Torso Ischemia and Reperfusion in Humans

Abstract

Background: An increase in gut permeability can have serious consequences leading to sepsis and multiple organ failure. After lower torso ischemia an increase in gut permeability is seen in both animals and humans. There is proof that this can be modified by antioxidant supplementation. Methods: In this prospective, randomized study we have looked at the influence of a multiantioxidant supplementation regime, using allopurinol, vitamins E and C, mannitol and N-acetylcysteine, perioperatively. Twenty-two patients received standard treatment and 20 patients received supplementation. Gut permeability was determined using a double sugar test with lactulose and rhamnose. Results: A significant increase in gut permeability was found neither in the non-treatment group (p = 0.012) nor in the treatment group (p = 0.006) after 6 and 24 h. No difference was found between the group receiving antioxidants and the standard treatment group. p = 0.93 6 h post clamp; p = 0.97 24 h post clamp. Conclusion: In this study we have not found an influence of multiantioxidant supplementation on gut permeability after lower torso ischemia. Possible explanations for this negative result are being discussed.

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…Unfortunately, the above listed basic observations did not translate into the clinic. According to a recent randomized study by Wijnen et al (2002), a multiantioxidant supplementation regimen (containing allopurinol, as well as vitamins E and C, mannitol, and N-acetylcysteine) failed to affect the changes in gut permeability after lower torso ischemia.…”

Therapeutic Targeting of CD47 to Modulate Tissue Responses to Ischemia and Radiation

“…Several of the key elements that have emerged from these studies are the importance of maintaining blood flow, limiting inflammatory responses and the accompanying formation of reactive oxygen species (ROS), and limiting programmed cell death responses in tissues that are temporarily deprived of oxygen and nutrients. Correspondingly, nitric oxide (NO) and NO donor drugs have been used to increase blood flow, anti-inflammatory agents to limit recruitment or activation of neutrophils, antioxidants to scavenge ROS, and anti-apoptotic agents to minimize loss of viable cells in ischemic tissues [1–4]. Unfortunately, such approaches to date have demonstrated limited success in clinical use [1,2].…”

“…Correspondingly, nitric oxide (NO) and NO donor drugs have been used to increase blood flow, anti-inflammatory agents to limit recruitment or activation of neutrophils, antioxidants to scavenge ROS, and anti-apoptotic agents to minimize loss of viable cells in ischemic tissues [1–4]. Unfortunately, such approaches to date have demonstrated limited success in clinical use [1,2]. Therefore, a deeper understanding is needed of the signaling pathways that limit tissue survival under such conditions.…”

Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion

“…It is noteworthy that despite extensive research for over two decades on oxygen-free radicals and neutrophils, clinical trials of antioxidants or antineutrophil therapy have not had much success in reducing I/R injury in various organs. [31][32][33][34] Oxidative respiratory bursts in neutrophils are characterized by the production of superoxide, hydrogen peroxide and hypochlorous acids. The synthesis of free oxidative radicals is catalyzed by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO).…”