Evaluation of Putative Biomarkers of Nephrotoxicity after Exposure to Ochratoxin A In Vivo and In Vitro

Abstract

The kidney is one of the main targets of xenobiotic-induced toxicity, but early detection of renal damage is difficult. Recently, several novel biomarkers of nephrotoxicity have been identified by transcription profiling, including kidney injury molecule-1 (Kim-1), lipocalin-2, tissue inhibitor of metalloproteinases-1 (Timp-1), clusterin, osteopontin (OPN), and vimentin, and suggested as sensitive endpoints for acute kidney injury in vivo. However, it is not known if these cellular marker molecules may also be useful to predict chronic nephrotoxicity or to detect nephrotoxic effects in vitro. In this study, a panel of new biomarkers of renal toxicity was assessed via quantitative real-time PCR, immunohistochemistry, and immunoblotting in rats treated with the nephrotoxin ochratoxin A (OTA) for up to 90 days and in rat proximal tubule cells (NRK-52E) treated with OTA in vitro. Repeated administration of OTA to male F344/N rats for 14, 28, or 90 days resulted in a dose- and time-dependent increase in the expression of Kim-1, Timp-1, lipocalin-2, OPN, clusterin, and vimentin. Changes in gene expression were found to correlate with the progressive histopathological alterations and preceded effects on traditional clinical parameters indicative of impaired kidney function. Induction of Kim-1 messenger RNA expression was the earliest and most prominent response observed, supporting the use of this marker as sensitive indicator of chronic kidney injury. In contrast, no significant increase in the expression of putative marker genes and proteins were evident in NRK-52E cells after exposure to OTA for up to 48 h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.

Ruta graveolens Protects Against Isoniazid/Rifampicin-Induced Nephrotoxicity through Modulation of Oxidative Stress and Inflammation

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

“…58 The occurrence of albuminuria has been shown to precede the increase of urinary NAG and serum creatinine. 59 A drawback of urine albumin, as marker of AKI, is its presence also in chronic renal failure.…”

Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: pharmaceutical, biological, and toxicological studies

“…58 Such toxicity is partly due to the high renal blood flow rate, which leads to delivery of high concentrations of xenobiotics to the kidneys. 59 Regarding kidney functions, serum urea and creatinine, the traditional kidney function tests, were assessed. Both blank and PIP-loaded cubs formulations treated groups showed no nephrotoxic effect indicating safety of the prepared formulations ( Table 7).…”