title: Reversal of radiocontrast medium toxicity in human renal proximal tubular cells by white grape juice extract.
abstract: Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical problem accounting for 12% of all hospital-acquired cases of acute kidney injury. The pathophysiology of CIN is not well understood, but direct toxic effects on renal cells have been postulated as contributing to CIN. We have investigated the effect of a white grape (Vitis vinifera) juice extract (WGJe) on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. WGJe caused an increase in phosphorylation of the prosurvival kinases Akt and ERK1/2 in HK-2 cells. Treatment of HK-2 cells with 75 mgI/ml sodium diatrizoate for 2.5h and then further incubation (for 27.5h) after removal of the RCM caused a drastic decrease in cell viability. However, pre-treatment with WGJe, prior to incubation with diatrizoate, dramatically improved cell viability. Analysis of key signaling molecules by Western blotting showed that diatrizoate caused a drastic decrease in phosphorylation of Akt (Ser473), FOXO1 (Thr24) and FOXO3a (Thr32) during the initial 2.5h incubation period, and WGJe pre-treatment caused a reversal of these effects. Further analysis by Western blotting of samples from HK-2 cells cultured for longer periods of time (for up to 27.5h after an initial 2.5h exposure to diatrizoate with or without WGJe pre-treatment) showed that WGJe pre-treatment caused a negative effect on phosphorylation of p38, NF-κB (Ser276) and pERK1/2 whilst having a positive effect on the phosphorylation of Akt, FOXO1/FOXO3a and maintained levels of Pim-1 kinase. WGJe may alleviate RCM toxicity through modulation of signaling molecules that are known to be involved in cell death and cell survival and its possible beneficial effects should be further investigated.
authors.affiliation: Department of "Health Sciences", Nephrology Unit, Magna Graecia University, Catanzaro I-88100, Italy. Electronic address: andreucci@unicz.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Andreucci
authors.affiliation: Department of "Health Sciences", Nephrology Unit, Magna Graecia University, Catanzaro I-88100, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Faga
authors.affiliation: Department of "Public Health", Nephrology Unit, Federico II University, Naples I-80131, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.affiliation: Department of "Public Health", Nephrology Unit, Federico II University, Naples I-80131, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
authors.affiliation: Department of "Public Health", Nephrology Unit, Federico II University, Naples I-80131, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Food Quality and Nutrition, Fondazione Edmund Mach, Research and Innovation Centre, San Michele all'Adige, I-38010, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mattivi
authors.affiliation: Department of "Health Sciences", Pharmacology Unit, Magna Graecia University, Catanzaro I-88100, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Department of "Drug Sciences and Products for Health", 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, Catanzaro I-88100, Italy.
authors.forename: Ashour
authors.initials: A
authors.lastname: Michael
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D001628:Beverages / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D003973:Diatrizoate / Q000633:toxicity*; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D027843:Vitis / Q000737:chemistry*
chemical_list: D003287:Contrast Media; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D010936:Plant Extracts; D020011:Protective Agents; D003973:Diatrizoate; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell injury; Kinase; Renal cell; Signaling; Vitis spp.