Beatriz Prieto-Moure, Dolores Cejalvo-Lapeña, Lajara-Romance J.M., Elena Bover-Arbona, Daniel López-Maloa Carolina Padrón-Sanz, Javier Torres Gavilà and José Miguel Lloris- Carsíi
Facultad de Medicina, Universidad Católica de Valencia “San Vicente Mártir”, C/ Quevedo, 2. 46003. Valencia, Spain
Ischemia-reperfusion (IRI) is a complex physiopathological mechanism involving a large number of metabolic processes that can eventually lead to cell apoptosis and ultimately tissue necrosis.
Treatment approaches intended to reduce or palliate the effects of IRI are varied, and are aimed basically at: inhibiting cell apoptosis and the complement system in the inflammatory process deriving from IRI; modulating calcium levels; maintaining mitochondrial membrane integrity; reducing the oxidative effects of IRI and levels of inflammatory cytokines; or minimizing the action of macrophages, neutrophils, and other cell types.
This study involved an extensive, up-to-date review of the bibliography on the currently most widely used active ingredients in the treatment and prevention of IRI, and their mechanisms of action, in an aim to obtain an overview of current and potential future treatments for this pathological process.
Active ingredients are classified by mechanism of action into three groups:
1) Substances and mechanisms of action that modify the membrane response of IRI-affected cells:
· Antioxidants
· Reduction of inflammatory cytokines IL, TNF, and NK-κβ
· Na+/H+ (NHE) inhibitors
· Calcium modifiers
· Toll-like receptors
2) Substances and mechanisms of action that act on cells that lead to IRI:
· Prevention of leukocyte adhesion
· Inhibition of the complement system
· Depletion of macrophages/neutrophils
· Stem cell treatment
3) Special treatments in IRI
· Preconditioning
· Apoptosis inhibition
· Gene therapy
· miRNAs
· Natural therapies
· Mitochondrial membrane pore inhibitors
· Other treatments