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

Zsolt Ráduly; András Szabó; Miklós Mézes; Ildikó Balatoni; Robert G Price; Mark E Dockrell; István Pócsi; László Csernoch

doi:10.3389/fmicb.2023.1085818

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

Front Microbiol. 2023 Apr 14:14:1085818. doi: 10.3389/fmicb.2023.1085818. eCollection 2023.

Authors

Zsolt Ráduly^{1

2

3}, András Szabó^{4

5}, Miklós Mézes^{5

6}, Ildikó Balatoni⁷, Robert G Price⁸, Mark E Dockrell^{9

10}, István Pócsi¹¹, László Csernoch¹

Affiliations

¹ Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
² ELKH-DE Cell Physiology Research Group, University of Debrecen, Debrecen, Hungary.
³ Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary.
⁴ Agrobiotechnology and Precision Breeding for Food Security National Laboratory, Department of Physiology and Animal Health, Institute of Physiology and Nutrition, Hungarian University of Agriculture and Life Sciences, Kaposvár, Hungary.
⁵ ELKH-MATE Mycotoxins in the Food Chain Research Group, Kaposvár, Hungary.
⁶ Department of Food Safety, Institute of Physiology and Nutrition, Hungarian University of Agriculture and Life Sciences, Gödöllő, Hungary.
⁷ Clinical Center, University of Debrecen, Debrecen, Hungary.
⁸ Department of Nutrition, Franklin-Wilkins Building, King's College London, London, United Kingdom.
⁹ SWT Institute of Renal Research, London, United Kingdom.
¹⁰ Department of Molecular and Clinical Sciences, St. George's University, London, United Kingdom.
¹¹ Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary.

Abstract

The gradual spread of Aspergilli worldwide is adding to the global shortage of food and is affecting its safe consumption. Aspergillus-derived mycotoxins, including aflatoxins and ochratoxin A, and fumonisins (members of the fusariotoxin group) can cause pathological damage to vital organs, including the kidney or liver. Although the kidney functions as the major excretory system in mammals, monitoring and screening for mycotoxin induced nephrotoxicity is only now a developmental area in the field of livestock feed toxicology. Currently the assessment of individual exposure to mycotoxins in man and animals is usually based on the analysis of toxin and/or metabolite contamination in the blood or urine. However, this requires selective and sensitive analytical methods (e.g., HPLC-MS/MS), which are time consuming and expensive. The toxicokinetic of mycotoxin metabolites is becoming better understood. Several kidney biomarkers are used successfully in drug development, however cost-efficient, and reliable kidney biomarkers are urgently needed for monitoring farm animals for early signs of kidney disease. β₂-microglobulin (β₂-MG) and N-acetyl-β-D-glucosaminidase (NAG) are the dominant biomarkers employed routinely in environmental toxicology research, while kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as effective markers to identify mycotoxin induced nephropathy. Pigs are exposed to mycotoxins due to their cereal-based diet and are particularly susceptible to Aspergillus mycotoxins. In addition to commonly used diagnostic markers for nephrotoxicity including plasma creatinine, NAG, KIM-1 and NGAL can be used in pigs. In this review, the currently available techniques are summarized, which are used for screening mycotoxin induced nephrotoxicity in farm animals. Possible approaches are considered, which could be used to detect mycotoxin induced nephropathy.

Keywords: KIM-1; NAG; NGAL biomarkers, mycotoxin induced nephrotoxicity; animal toxicity; kidney biomarkers; mycotoxins; nephrotoxicity.

Publication types

Review