Radiocontrast-induced DNA fragmentation of renal tubular cells in vitro: role of hypertonicity

Abstract

The DNA fragmentation of MDCK cells induced by diatrizoate is related to its hypertonicity in this in vitro model of radiocontrast cytotoxicity. Nuclear disintegration with subsequent cell death may contribute to the pathophysiology of radiocontrast-induced nephropathy, particularly in the hypertonic/hypoxic environment of the renal medulla. The present results underscore the importance of avoiding hyperosmolal urine states in patients at high risk of radiocontrast-induced nephropathy.

The potential use of biomarkers in predicting contrast-induced acute kidney injury

“…[11][12][13][14] The direct toxic effects of CM have been studied in various cells, including renal epithelial and mesangial cells. 15 The functional and structural changes observed as a result of CM action included cell death, a decrease in cell viability, and an increase in brush border and lysosomal enzyme activity; 16 cellular DNA fragmentation; 17 downregulation of signaling molecules involved in cell survival such as Akt and upregulation of signaling molecules in cell death such as the p38 and c-Jun N-terminal kinase members of the mitogenactivated protein kinases and the transcription factor nuclear factor kB as well as caspase activation. 13,18,19 Nuclear factor kB and c-Jun N-terminal kinases are believed to be involved in the upregulation of the proinflammatory cytokine interleukin-8 (IL-8).…”

“…Cell cycle arrest may result as a consequence of cellular damage, in particular DNA damage, thus preventing the cell from entering cell division. Cellular DNA damage by CM has been reported; 17 and therefore, it is feasible that the CM may upregulate these cell cycle arrest markers in renal tubule cells and may be detected in urine after CM-induced renal injury.…”

Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies

“…In addition, in an in vitro model with a renal epithelial cell line, DNA fragmentation (a marker of apoptosis) was increased in cells exposed to hyperosmolar contrast media, and the degree of fragmentation was proportional to the osmolality of the contrast medium. 36 Thus, there is evidence of a direct cytotoxic effect of contrast media that is independent of hypoxia and may be related to hyperosmolality of the contrast agent. However, when the renal effects of isoosmolar contrast media, which have the lowest osmolality, were compared with the effects of hypo-and hyperosmolar contrast agents, there was no reduction in renal abnormalities with the iso-osmolar agents.…”

N-Acetylcysteine In The Prevention Of Radiocontrast-Induced Nephropathy

“…Radiocontrast results in apoptosis of tubular epithelial cells in vivo (54) and in cultured cells (47,55). Hizoh et al (47) found that contrast-induced apoptosis in cultured cells was due to hyperosmolarity and not hypoxia. In contrast, other studies have found that epithelial cell apoptosis occurs after contrast-induced decreases in medullary oxygenation (54).…”