title: Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media.
abstract: Modern iodinated radiocontrast media are all based on the triiodinated benzene ring with various chemical modifications having been made over the last few decades in order to reduce their toxicity. However, CIN remains a problem especially in patients with pre-existing renal failure. In vitro studies have demonstrated that all RCM are cytotoxic. RCM administration in vivo may lead to a decrease in renal medullary oxygenation leading to the generation of reactive oxygen species that may cause harmful effects to renal tissue. In addition, endothelin and adenosine release and decreased nitric oxide levels may worsen the hypoxic milieu. In vitro cell culture studies together with sparse in vivo rat model data have shown that important cell signalling pathways are affected by RCM. In particular, the prosurvival and proproliferative kinases Akt and ERK1/2 have been shown to be dephosphorylated (deactivated), whilst proinflammatory/cell death molecules such as the p38 and JNK kinases and the transcription factor NF- κ B may be activated by RCM, accompanied by activation of apoptotic mediators such as caspases. Increasing our knowledge of the mechanisms of RCM action may help to develop future therapies for CIN.
authors.affiliation: Department of Health Sciences, Nephrology Unit, "Magna Graecia" University, I-88100 Catanzaro, Italy.
authors.forename: Ashour
authors.initials: A
authors.lastname: Michael
authors.affiliation: Department of Health Sciences, Nephrology Unit, "Magna Graecia" University, I-88100 Catanzaro, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Faga
authors.affiliation: Department of Nephrology, "Federico II" University, I-80131 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.affiliation: Department of Nephrology, "Federico II" University, I-80131 Naples, Italy.
authors.forename: Eleonora
authors.identifier: 0000-0002-5379-1104
authors.initials: E
authors.lastname: Riccio
authors.affiliation: IRCCS Centro Neurolesi "Bonino Pulejo", I-98124 Messina, Italy.
authors.forename: Placido
authors.identifier: 0000-0003-0394-8166
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: Department of Nephrology, "Federico II" University, I-80131 Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, I-98168 Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
authors.affiliation: Department of Health Sciences, Nephrology Unit, "Magna Graecia" University, I-88100 Catanzaro, Italy.
authors.forename: Michele
authors.identifier: 0000-0002-7974-3792
authors.initials: M
authors.lastname: Andreucci
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D003287:Contrast Media / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D003287:Contrast Media; D016207:Cytokines
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