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: Michele Andreucci, Teresa Faga, Antonio Pisani, Massimo Sabbatini, Domenico Russo, Fulvio Mattivi, Giovambattista De Sarro, Michele Navarra, Ashour Michael
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 229 Pg. 17-25 (Mar 05 2015) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 25603236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Contrast Media
• FOXO1 protein, human
• FOXO3 protein, human
• Forkhead Box Protein O1
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Plant Extracts
• Protective Agents
• Diatrizoate
• Proto-Oncogene Proteins c-akt

Topics

• Acute Kidney Injury (chemically induced)
• Beverages (analysis)
• Cell Line
• Cell Survival (drug effects)
• Contrast Media (toxicity)
• Diatrizoate (toxicity)
• Forkhead Box Protein O1
• Forkhead Box Protein O3
• Forkhead Transcription Factors (metabolism)
• Humans
• Kidney Tubules, Proximal (cytology, drug effects, metabolism, pathology)
• Phosphorylation (drug effects)
• Plant Extracts (isolation & purification, pharmacology)
• Protective Agents (isolation & purification, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Vitis (chemistry)