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WUTH publication: Zinc induced damage to kidney proximal tubular cells: Studies on chemical speciation leading to a mechanism of damage.

Citation: Journal of Trace Elements in Medicine and Biology, 2013, 27(3), 242-8
Author: Sargazi M, Shenkin A, Roberts NB
Abstract: This study was carried out to investigate whether zinc can potentiate renal toxicity using monolayer cultures of kidney proximal tubular cells and if so to establish the chemical species and the mechanism involved. METHODS: Zinc was prepared as the citrate complex at pH 7.4 in phosphate buffered saline. Monolayers of kidney proximal tubular cells under standard cell culture conditions were exposed to zinc concentrations of 0, 5 10, 20, 50 and 100μmol/L. To assess cellular damage, thiazol blue (MTT) uptake, NAG and LDH release, DAPI staining and Tunel assay were used. Cytoprotective agents: trolox, cysteine, glutathione, ascorbic acid and sodium selenite were used to investigate if the damage was reversible. RESULTS: Incubation of kidney cells with zinc citrate showed a dose related reduction in cell viability (p<0.005) associated with cellular uptake of zinc ions. After 24h incubation with 100μmol/L Zn citrate, NAG release was not significantly different compared to the control whereas LDH increased 3 fold. DAPI staining showed apoptotic bodies within the cells confirmed by Tunel assay using flow cytometry. Electron microscopy showed significant morphological changes including loss of brush border, vacuolated cytoplasm and condensed nuclei. Trolox almost completely (>85±5%) and sodium selenite partially recovered (40±4%) the viability of cells exposed to Zn but no protection was observed with other cytoprotectants, e.g. glutathione, cysteine or ascorbic acid. In conclusion zinc can induce damage to kidney cells by a mechanism dependent on zinc ions entering the cell, binding to the cell organelles and disrupting cellular processes rather than damage initiated by free radical and ROS production.

Link to Pubmed record 

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Final report of the Mid Staffordshire NHS Foundation Trust Public Inquiry (Francis report)

The final report of the Mid Staffordshire NHS Foundation Trust Public Inquiry, conducted by Robert Francis QC, was published on Wednesday 6 February 2013.  His Inquiry followed concerns about standards of care at the Trust, and an investigation and report published by the Healthcare Commission in March 2009.  Robert Francis has heard evidence from patients, their relatives and staff to inform his report and the 18 recommendations he makes.

Read the full report here.

The Guardian website gives a useful overview of the key recommendations from the report.

The Department of Health has published three reports to help embed effective governance and detect and prevent such serious failures occurring again: Review of Early Warning Systems in the NHS, Assuring the quality of senior NHS managers, The Healthy NHS Board.

Read the Care Quality Commission's response to the report here.