Role of Contrast Media on Oxidative Stress, Ca2+ Signaling and Apoptosis in Kidney

Abstract

Contrast media (CM)-induced nephropathy is a common cause of iatrogenic acute renal failure. The aim of the present review was to discuss the mechanisms and risk factors of CM, to summarize the controlled studies evaluating measures for prevention and to conclude with evidence-based strategies for prevention. A review of the relevant literature and results from recent clinical studies as well as critical analyses of published systematic reviews used MEDLINE and the Science Citation Index. The cytotoxicity induced by CM leads to apoptosis and death of endothelial and tubular cells and may be initiated by cell membrane damage together with reactive oxygen species (ROS) and inflammation. Cell damage may be aggravated by factors such as tissue hypoxia, properties of individual CM such as ionic strength, high osmolarity and/or viscosity. Clinical studies indeed support this possibility, suggesting a protective effect of ROS scavenging with the administration of N-acetylcysteine, ascorbic acid erdosteine, glutathione and bicarbonate infusion. The interaction between extracellular Ca(2+), which plays a central role in intercellular contacts and production of ROS, and the in vitro toxicity of CM was also reviewed. The current review addresses the role of oxidative stress in the pathogenesis of CM in the kidney as well as current and potential novel treatment modalities for the prevention of neutrophil activation and CM-induced kidney degeneration in patients. ROS production through CM-induced renal hypoxia may exert direct tubular and vascular endothelial injury. Preventive strategies via antioxidant supplementation include inhibition of ROS generation or scavenging.

Tnf-α inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy

“…In several studies, tubular necrosis and epithelial damage were shown to be major indicators in nephrotoxicity damage (Naziroglu et al, 2013). In studies seeking to identify the tubular epithelial injury, tubular necrosis, hyaline casts, and haemorrhagic casts were investigated (Droguett et al, 2014).…”

“…It has been reported that pro-inflammatory mediators, such as TNF-α, IL-1β, and TGF-1β, are produced in acute I/R injury due to tubular and endothelial cellular damage, and these inflammatory cytokines contribute to the enhancement of renal injury (Bonventre, 2004). In CM-induced renal injury, tubular and endothelial cellular damage are observed, similar to other renal injuries (Naziroglu et al, 2013). Anti-cytokine treatment has been tried experimentally for renal injuries caused by nephrotoxic substances and has been shown to potentially decrease the severity of renal injury (Di Paola et al, 2013).…”

Zinc Chloride Inhibits Human Lens Epithelial Cell Migration and Proliferation Involved in TGF-β1 and TNF-α Signaling Pathways in HLE B-3 Cells

“…Under many kinds of cellular stresses, unfolded proteins are accumulated in the ER and influence normal ER functions [10,11]. Activation of caspase-12 plays a role in the triggering of apoptosis by the intrinsic ER stress apoptotic pathway, which is mediated by ER through activation of the caspase-9-and caspase-3-dependent pathways.…”

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

“…In various studies, tubular necrosis and epithelial injury have been shown to be significant indicators in nephrotoxicity injury; 53 tubular epithelial damage, tubular necrosis, hyaline and haemorrhagic casts have been found in these investigations. 54 In the development of nephropathy, significant damage to haemorrhagic renal tubules with hyaline occurs and is related to tubular injury.…”