Title:Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events
Volume: 23
Issue: 19
Author(s): Branislav Rovcanin, Branislava Medic, Gordana Kocic, Tatjana Cebovic, Marko Ristic and Milica Prostran
Affiliation:
Keywords:
Ischemic reperfusion kidney injury, inflammation, oxidative stress, antioxidant defense, mitochondria,
heat-shock proteins, MicroRNAs, gene expresión.
Abstract: Ischemic reperfusion kidney injury (IRKI) is a complex
pathophysiological event, which is the most common cause of the acute kidney
injury. The key characteristic of IRKI is a reduction in glomerular filtration rate,
which implies an underlying impairment in hemodynamic regulation. In recent
decades, convincing evidence illuminated the molecular and pathological events
in the acute kidney injury, revealing the role of ischemia/reperfusion, oxidative
stress, apoptosis, inflammation, fibrosis and changes in gene expression which
activate different signaling pathways. The cascade of inflammation events is a
key mediator of IRKI, which includes the inflammation process, complement
activation and mobilization of innate immunity. Oxidative stress represents
the increased presence of various free radicals that cannot be buffered by the antioxidant capacity
which comprises of enzymatic and non-enzymatic components. Renal tissue injury during
ischemia/reperfusion comes as a result of membrane lipids peroxidation, oxidative damage of
proteins and DNA and results in apoptosis and necrosis. It is evident from many studies that
augmentation of the antioxidant defense mechanisms has a protective role on kidney tissue. In
recent years, the importance of heat-shock proteins and MicroRNAs in the pathogenesis of IRKI
has been revealed and there are promising indications that in future they could serve as diagnostic
biomarkers or therapeutic targets. Striking changes in global gene expression were shown,
providing a great potential for fundamental understanding and clinical management of IRKI. The
clinical outcome among patients with kidney transplantation will have the furthermost advance
from the better understanding of the underlying molecular pathology of IRKI.