Abstract
Organ replacement is an option to mitigate irreversible organ damage. This procedure has achieved a considerable degree of acceptance. However, several factors significantly limit its effectiveness. Among them, the initial inflammatory graft reaction due to ischemia-reperfusion injury (IRI) has a fundamental influence on the short and long term organ function. The reactive oxygen species (ROS) produced during the IRI actively participates in these adverse events. Therapeutic strategies that tend to limit the action of free radicals could result in beneficial effects in transplantation outcome. Accordingly, the anti-oxidant α-lipoic acid (ALA) have been proved to be protective in several animal experimental models and humans. In a clinical trial, ALA was found to decrease hepatic IRI after hepatic occlusion and resection. Furthermore, the treatment of cadaveric donor and recipient with ALA had a protective effect in the short-term outcome in simultaneous kidney and pancreas transplanted patients. These studies support ALA as a drug to mitigate the damage caused by IRI and reinforce the knowledge about the deleterious consequences of ROS on graft injury in transplantation. The goal of this review is to overview the current knowledge about ROS in transplantation and the use of ALA to mitigate it.
Highlights
During the transplantation procedure, the organs undergo ischemia-reperfusion injury (IRI)
Summary of the Experimental IRI Models. These IRI animal models, supports the concept that reactive oxygen species (ROS) could be an appropriate target to decrease tissue injury caused by the ischemia
These animal models, allow us to understand the putative molecular pathway involves in the effect of anti-oxidant α-lipoic acid (ALA) on IRI, which includes the PI3K/Akt/nuclear factor erythroid 2–related factor 2 (Nrf2) pathways that controls the expression of genes involves in the detoxification and elimination of ROS and electrophilic agents
Summary
Imbalances of the cellular ions take place, activation of hydrolases and a critical increase in the permeability of the cells membrane [3,4,5,6]. These events follow only in part a sequential order and self-amplification of processes and propagation can occur through various pathways. Cellular homeostasis of ions deteriorates, implying an increase in the cytosolic concentrations of Na+ and Ca2+ The latter activates hydrolases, such as phospholipase A2 and proteases [3] and proteolysis of cytoskeletal proteins favors the process of tissue injury. The rise of cellular Na+ cause edema, that contributes to the damage of the plasma membrane resulting in the cell death by necrosis [7]
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