Oxidative Stress in Hepatic Ischemia-Reperfusion Injury: The Role of Antioxidants and Iron Chelating Compounds

Abstract

Ischemia-reperfusion (IR) injury is a multifactorial process triggered when the liver or other organs are transiently subjected to reduced blood supply followed by reperfusion. It has been shown that "reactive oxygen species" (ROS) are generated during ischemia and reperfusion and may represent pivotal mediators of the ensuing pathological complications. In some cases, however, moderate production of ROS may exert protective effects, a phenomenon presumably related to "ischemic preconditioning". This review will focus mainly on: a) describing the sources and the biochemical mechanisms of ROS generation during ischemia and reperfusion, b) discussing current developments in understanding the biochemical pathways by which ROS may induce toxic or protective effects, c) critically evaluating the results of previous attempts to counteract the toxic effects of ROS by using a variety of antioxidant and transition metalchelating agents, and d) if feasible, proposing potential new pharmaceutical agents aimed at ameliorating ROS-inducing deleterious effects during reperfusion. It is concluded that ROS are generated from different sources, at different periods during IR, and may act by a variety of not well understood biochemical mechanisms which ultimately lead to cell damage and tissue failure.

A New Ghost Cell/Level Set Method for Moving Boundary Problems: Application to Tumor Growth

“…We wish to solve quasi-steady reaction-diffusion problems of the form (18) coupled with standard (e.g., Dirichlet, Neumann, or extrapolation) boundary conditions on ∂ . (Note that D and p are scalars, i.e., D = D i and p = p i for some fixed 1 ≤ i ≤ k in the notation of (1).)…”

“…A similar extension to the ghost cell method was presented in [19] to solve Laplace's equation without geometric boundary conditions and yielded fourth-order convergence on fixed domains and third-order convergence on moving boundaries. In [38], we extended our approach to solve systems like (18) in the case where h = 0 and D was constant in Ω and Ω c (with different constants). We applied the method to model avascular tumor growth in [38] and verified second-order accuracy for our overall solutions, although our method numerically smeared jumps in the tangential derivative.…”

“…If the tumor continues to grow and the interior nutrient level drops further below a critical threshold c N , the tumor cells begin to die (necrose). When cells necrose, they release their cellular contents, which are both oxygen-reactive (e.g., see [18,29]) and growth-inhibiting. These processes can be modeled as…”

Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-Dependent Mechanism

“…(12) The best understood mechanism, however, functions through the enzyme xanthine oxidase (XO), whose expression is highest in the liver, and its substrate hypoxanthine: each enzymatic cycle yields 2 molecules of superoxide. (13,(19)(20)(21) Superoxide and other ROS are believed to be the principal mediators of I/R injury, (22) and XO is believed to be the principal source of these oxidative intermediates in the liver. (19)(20)(21) High concentrations of superoxide upregulate the expression of endothelial adhesion proteins, (23,24) thereby promoting neutrophil recruitment and accumulation in an ischemic liver lobe.…”

Nonlinear simulation of the effect of microenvironment on tumor growth

“…However, necrosing cells release their intracellular contents, which are both cytotoxic/growth-inhibiting (Freyer, 1988;Festjens et al, 2006) and oxygen-reactive (e.g., necrotic tissue rapidly reacts with reintroduced oxygen to form reactive oxygen species that react with and damage biological molecules (Kloner and Jennings, 2001;Galaris et al, 2006)). Recalling that the general nutrient c models the net effect of nutrients and growth-promoting and inhibiting factors, we can model these effects with a nutrient decay rate λ D .…”