Urinary Biomarkers of Mycotoxin Induced Nephrotoxicity—Current Status and Expected Future Trends

Abstract

The intensifying world-wide spread of mycotoxigenic fungal species has increased the possibility of mycotoxin contamination in animal feed and the human food chain. Growing evidence shows the deleterious toxicological effects of mycotoxins from infants to adults, while large population-based screening programs are often missing to identify affected individuals. The kidney functions as the major excretory system, which makes it particularly vulnerable to nephrotoxic injury. However, few studies have attempted to screen for kidney injury biomarkers in large, mycotoxin-exposed populations. As a result, there is an urgent need to screen them with sensitive biomarkers for potential nephrotoxicity. Although a plethora of biomarkers have been tested to estimate the harmful effects of a wide spectrum of toxicants, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are currently the dominant biomarkers employed routinely in environmental toxicology research. Nevertheless, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as useful and informative markers to reveal mycotoxin induced nephrotoxicity. In this opinion article we consider the nephrotoxic effects of mycotoxins, the biomarkers available to detect and quantify the kidney injuries caused by them, and to recommend biomarkers to screen mycotoxin-exposed populations for renal damage.

High‐pressure acidified steaming with varied citric acid dosing can successfully detoxify mycotoxins

“…Loboda et al ( 2017 ) reported the nephrotoxic effects of OTA on porcine tubular epithelial cells after Nrf2 inhibition with reduced vascular endothelial growth factor and claudin‐2 levels and increased expression of proapoptotic, profibrotic, and proinflammatory factors. In other studies, DNA microarray analysis following the proximal tubular cells double fluorescence labeling of primary rat and Wistar rats treated with several ochratoxin A doses showed transcriptional changes in genes involved in apoptosis, inflammatory reactions, and DNA damage responses (Gan et al, 2022 ; Ráduly et al, 2021 ). Real‐time polymerase chain reactions application in studying the expression of gene responsible for cell division and cell control in OTA‐treated male F344 rats at doses of 210, 70, 21, and 0 mg/kg of body weight showed that OTA induces the expression of excess mitosis key regulators, such as aurora B kinase, cyclin's kinase‐dependent inhibitors, serine/threonine protein kinase PLK1, surviving, topoisomerase II, cyclin‐dependent kinase 1 (Cdk1Cdc2), and cyclins with some key regulators' upregulation in the proximal tubular S3 cell, where OTA‐induced tumors appear (EFSA Panel on Contaminants in the Food Chain (CONTAM) et al, 2020 ; Khoi et al, 2021 ).…”

New perspectives in application of kidney biomarkers in mycotoxin induced nephrotoxicity, with a particular focus on domestic pigs

“…Urinary NAG is the predominant enzyme assay used in screening programs and is well suited for screening in low GDP countries. KIM-1 lateral-flow strip tests can be also used for screening programs (see Table 2; Wasung et al, 2015;Ráduly et al, 2021;Pócsi et al, 2022).…”

Revisiting the Role of NAG across the Continuum of Kidney Disease

“…The high blood flow rate makes the kidneys susceptible to nephrotoxic substances, which are widely distributed in the environment. Tobacco smoking, environmental pollutants, and occupational-linked toxins such as metals, aristolochic acid, mycotoxins, and solvents alike, are major contributors to this public health issue [ 86 ].…”