Deoxynivalenol (DON) is a mycotoxin that frequently contaminates food crops and negatively impacts human and animal health. While inositol-6-phosphate (IP6) is known to counteract DON-induced intestinal damage, inflammation, and oxidative stress, its ability to alleviate DON-caused kidney injury is yet unexplored. This study assessed DON’s kidney effects and IP6’s protective capability using an ex vivo renal explants model. From 360 explants taken from six pigs, four groups were formed: control (culture medium), DON (10 μM equivalent to 3 mg/kg of feed), IP6 group (5 mM), and DON + IP6 (10 μM + 5 mM). DON elevated creatinine levels and γ-glutamyl transferase activity in the culture medium. It led to cytoplasmic vacuolation in convoluted tubular epithelial cells and tubular necrosis, a drop in antioxidant potential (ABTS) and a rise in interleukin (IL)-8 mRNA. The introduction of IP6 restored renal histological and functional parameters, bolstered antioxidant status, enhanced IL-10 gene expression, and reduced superoxide anion levels. These results indicate that within the model of renal explants, IP6 significantly alleviates the nephrotoxic effects of DON while efficiently regulating the antioxidative and anti-inflammatory response within the kidneys.
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Abdel-Hamid, N.M., Faddah, L.M., Al-Rehany, M.A., Ali, A.H. and Bakeet, A.A., 2007. New role of antinutritional factors, phytic acid and catechin in the treatment of CCl4 intoxication. Annals of Hepatology 6: 262-266. https://doi.org/10.1016/S1665-2681(19)31908-8
Abu El-Saad, A.S. and Mahmoud, H.M., 2009. Phytic acid exposure alters aflatoxin B1-induced reproductive and oxidative toxicity in albino rats (Rattus norvegicus). Evidence-Based Complementary and Alternative Medicine 6: 331-341. https://doi.org/10.1093/ecam/nem137
Accensi, F., Pinton, P., Callu, P., Abella-Bourges, N., Guelfi, J.F., Grosjean, F. and Oswald, I.P., 2006. Ingestion of low doses of deoxynivalenol does not affect hematological, biochemical, or immune responses of piglets. Journal of Animal Science 84: 1935-1942. https://doi.org/10.2527/jas.2005-355
Alassane-Kpembi, I., Canlet, C., Tremblay-Franco, M., Jourdan, F., Chalzaviel, M., Pinton, P., Cossalter, A.M., Achard, C., Castex, M., Combes, S., Bracarense, A.P.L. and Oswald, I.P., 2020. (1)H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation. Food and Chemical Toxicology 138: 111222. https://doi.org/10.1016/j.fct.2020.111222
Alizadeh, A., Braber, S., Akbari, P., Garssen, J. and Fink-Gremmels, J., 2015. Deoxynivalenol impairs weight gain and affects markers of gut health after low-dose, short-term exposure of growing pigs. Toxins 7: 2071-2095. https://doi.org/10.3390/toxins7062071
Biomin, 2023. Biomin Mycotoxin Survey Q3 2021 Results. Available at: https://www.biomin.net/science-hub/biomin-mycotoxin-survey-q3-2021-results/.
Caceres, I., El Khoury, R., Medina, Á., Lippi, Y., Naylies, C., Atoui, A., El Khoury, A., Oswald, I.P., Bailly, J.D. and Puel, O., 2016. Deciphering the anti-aflatoxinogenic properties of eugenol using a large-scale q-PCR approach. Toxins 8: 123. https://doi.org/10.3390/toxins8050123
Da Silva, E., Santos, J., Morey, A., Yamauchi, L. and Bracarense, A.L., 2021. Phytic acid modulates the morphology, immunological response of cytokines and β-defensins in porcine intestine exposed to deoxynivalenol and fumonisin B1. World Mycotoxin Journal 14: 441-450. https://doi.org/10.3920/WMJ2020.2648
Da Silva, E.O., Gerez, J.R., do Carmo Drape, T. and Bracarense, A., 2014. Phytic acid decreases deoxynivalenol and fumonisin B1-induced changes on swine jejunal explants. Toxicology Reports 1: 284-292. https://doi.org/10.1016/j.toxrep.2014.05.001
Da Silva, E.O., Gerez, J.R., Hohmann, M.S.N., Verri, W.A., Jr. and Bracarense, A., 2019. Phytic acid decreases oxidative stress and intestinal lesions induced by fumonisin B1 and deoxynivalenol in intestinal explants of pigs. Toxins 11: 18. https://doi.org/10.3390/toxins11010018
Dänicke, S. and Brezina, U., 2013. Kinetics and metabolism of the Fusarium toxin deoxynivalenol in farm animals: consequences for diagnosis of exposure and intoxication and carry over. Food and Chemical Toxicology 60: 58-75. https://doi.org/10.1016/j.fct.2013.07.017
Deng, Y., You, L., Nepovimova, E., Wang, X., Musilek, K., Wu, Q., Wu, W. and Kuca, K., 2021. Biomarkers of deoxynivalenol (DON) and its modified form DON-3-glucoside (DON-3G) in humans. Trends in Food Science and Technology 110: 551-558. https://doi.org/10.1016/j.tifs.2021.02.038
Douglas, W.R., 1972. Of pigs and men and research: a review of applications and analogies of the pig, Sus scrofa, in human medical research. Space Life Science 3: 226-234. https://doi.org/10.1007/bf00928167
Fakier, S., Rodgers, A. and Jackson, G., 2019. Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments. Urolithiasis 47: 493-502. https://doi.org/10.1007/s00240-019-01117-1
Fæste, C.K., Ivanova, L., Sayyari, A., Hansen, U., Sivertsen, T. and Uhlig, S., 2018. Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data. Archives of Toxicology 92: 2195-2216. https://doi.org/10.1007/s00204-018-2220-1
Gerez, J.R., Desto, S.S. and Bracarense, A.P.F.R.L., 2017. Deoxynivalenol induces toxic effects in the ovaries of pigs: an ex vivo approach. Theriogenol 90: 94-100. https://doi.org/10.1016/j.theriogenology.2016.10.023
Gerez, J.R., Verri, W.A., Hohmann, M.S., Flaiban, K.M.C., Hasuda, A.L., Gloria, E.M. and Bracarense, A., 2022. Animal performance and biochemical parameters are sex-dependent in peripubertal rats exposed to deoxynivalenol. Toxicon 220: 106944. https://doi.org/10.1016/j.toxicon.2022.106944
Goyarts, T., Dänicke, S., Valenta, H. and Ueberschär, K.H., 2007. Carry-over of Fusarium toxins (deoxynivalenol and zearalenone) from naturally contaminated wheat to pigs. Food Additives and Contaminants 24: 369-380. https://doi.org/10.1080/02652030600988038
Grenier, B. and Applegate, T.J., 2013. Modulation of intestinal functions following mycotoxin ingestion: meta-analysis of published experiments in animals. Toxins 5: 396-430. https://doi.org/10.3390/toxins5020396
Grenier, B., Loureiro-Bracarense, A.-P., Lucioli, J., Pacheco, G.D., Cossalter, A.-M., Moll, W.-D., Schatzmayr, G. and Oswald, I.P., 2011. Individual and combined effects of subclinical doses of deoxynivalenol and fumonisins in piglets. Molecular Nutrition and Food Research 55: 761-771. https://doi.org/10.1002/mnfr.201000402
Holanda, D.M. and Kim, S.W., 2020. Efficacy of mycotoxin detoxifiers on health and growth of newly-weaned pigs under chronic dietary challenge of deoxynivalenol. Toxins 12: 311. https://doi.org/10.3390/toxins12050311
Jagdale, P.R., Dev, I., Ayanur, A., Singh, D., Arshad, M. and Ansari, K.M., 2020. Safety evaluation of ochratoxin A and citrinin after 28 days repeated dose oral exposure to Wistar rats. Regulatory Toxicology and Pharmacology 115: 104700. https://doi.org/10.1016/j.yrtph.2020.104700
Katalinic, V., Modun, D., Music, I. and Boban, M., 2005. Gender differences in antioxidant capacity of rat tissues determined by 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology 140: 47-52. http://doi.org/10.1016/j.cca.2005.01.005
Königs, M., Lenczyk, M., Schwerdt, G., Holzinger, H., Gekle, M. and Humpf, H.-U., 2007. Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture. Toxicology 240: 48-59. http://doi.org/10.1016/j.tox.2007.07.016
Larsen, C.G., Anderson, A.O., Appella, E., Oppenheim, J.J. and Matsushima, K., 1989. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science 243: 1464-1466. https://doi.org/10.1126/science.2648569
Li, X., Guo, Y., Zhao, L., Fan, Y., Ji, C., Zhang, J. and Ma, Q., 2018. Protective effects of Devosia sp. ANSB714 on growth performance, immunity function, antioxidant capacity and tissue residues in growing-finishing pigs fed with deoxynivalenol contaminated diets. Food and Chemical Toxicology 121: 246-251. https://doi.org/10.1016/j.fct.2018.09.007
Liang, Z., Ren, Z., Gao, S., Chen, Y., Yang, Y., Yang, D., Deng, J., Zuo, Z., Wang, Y. and Shen, L., 2015. Individual and combined effects of deoxynivalenol and zearalenone on mouse kidney. Environmental Toxicology and Pharmacology 40: 686-691. https://doi.org/10.1016/j.etap.2015.08.029
Ma, K., Bai, Y., Li, J., Ren, Z., Li, J., Zhang, J. and Shan, A., 2022. Lactobacillus rhamnosus GG ameliorates deoxynivalenol-induced kidney oxidative damage and mitochondrial injury in weaned piglets. Food and Function 13: 3905-3916. https://doi.org/10.1039/D2FO00185C
Maheshwar, P., Nandu, R., KR, S. and Adkar-Purushothama, C.R., 2018. Investigation of deoxynivalenol and its associated disturbances in urine creatinine.
Maidana, L.G., Gerez, J., Hohmann, M.N.S., Verri Jr., W.A. and Bracarense, A.P.F.L., 2021. Lactobacillus plantarum metabolites reduce deoxynivalenol toxicity on jejunal explants of piglets. Toxicon 203: 12-21. https://doi.org/10.1016/j.toxicon.2021.09.023.
Markiewicz, L.H., Ogrodowczyk, A.M., Wiczkowski, W. and Wróblewska, B., 2022. Phytate hydrolysate differently modulates the immune response of human healthy and cancer colonocytes to intestinal bacteria. Nutrients 14: 4234. https://doi.org/10.3390/nu14204234
Maruo, V.M., Bracarense, A.P., Metayer, J.-P., Vilarino, M., Oswald, I.P. and Pinton, P., 2018. Ergot alkaloids at doses close to eu regulatory limits induce alterations of the liver and intestine. Toxins 10: 183. https://doi.org/10.3390/toxins10050183
Perondi, F., Lippi, I., Ceccherini, G., Marchetti, V. and Guidi, G., 2019. Evaluation of urinary γ-glutamyl transferase and serum creatinine in non-azotaemic hospitalised dogs. Veterinary Record 185: 52. https://doi.org/10.1136/vr.104439
Pestka, J.J., 2010. Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Archives of Toxicology 84: 663-679. https://doi.org/10.1007/s00204-010-0579-8
Pestka, J.J., Zhou, H.R., Moon, Y. and Chung, Y.J., 2004. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicology Letters 153: 61-73. https://doi.org/10.1016/j.toxlet.2004.04.023
Pfohl-Leszkowicz, A. and Manderville, R.A., 2007. Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans. Molecular Nutrition and Food Research 51: 61-99. https://doi.org/10.1002/mnfr.200600137
Ran, X., Liu, J., Fu, S., He, F., Li, K., Hu, G. and Guo, W., 2022. Phytic acid maintains the integrity of the blood-milk barrier by regulating inflammatory response and intestinal flora structure. Journal of Agricultural and Food Chemistry 70: 381-391. https://doi.org/10.1021/acs.jafc.1c06270
Reddy, K.E., Lee, W., Jeong, J.Y., Lee, Y., Lee, H.J., Kim, M.S., Kim, D.W., Yu, D., Cho, A., Oh, Y.K. and Lee, S.D., 2018. Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets. Asian-Australasian Journal of Animal Sciences 31: 138-148. https://doi.org/10.5713/ajas.17.0454
Schelstraete, W., Devreese, M. and Croubels, S., 2020. Comparative toxicokinetics of Fusarium mycotoxins in pigs and humans. Food and Chemical Toxicology 137: 111140. https://doi.org/10.1016/j.fct.2020.111140
Schiffl, H. and Lang, S.M., 2012. Update on biomarkers of acute kidney injury. Molecular Diagnosis and Therapy 16: 199-207. https://doi.org/10.1007/BF03262209
Schmouder, R.L., Strieter, R.M., Wiggins, R.C., Chensue, S.W. and Kunkel, S.L., 1992. In vitro and in vivo interleukin-8 production in human renal cortical epithelia. Kidney International 41: 191-198. https://doi.org/10.1038/ki.1992.26
Sedlak, J. and Lindsay, R.H., 1968. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry 25: 192-205. https://doi.org/10.1016/0003-2697(68)90092-4
Soliman, H.A.E., Ahmed, R.R., Gomaa, H.A. and Ali, A.T., 2014. Assessment of the chemo-preventive effects of various plant constituents against doxorubicin-induced toxicity in rats. Journal of American Science 10: 153-164.
Suhett, W.G., Gerez, J.R., Hohmann, M.S., Staurengo-Ferrari, L., Verri, W.A., Pinho, F.H.O., de Barros, L.D., Cardim, S.T., Flaiban, K.M.C. and Bracarense, A.P.F.R.L., 2023. Exploring porcine kidney explants as a model for the study of nephrotoxins and the therapeutic potential of phytic acid. Environmental Toxicology and Pharmacology 102: 104241. https://doi.org/10.1016/j.etap.2023.104241
Sun, Y., Jiang, J., Mu, P., Lin, R., Wen, J. and Deng, Y., 2022. Toxicokinetics and metabolism of deoxynivalenol in animals and humans. Archives in Toxicology 96: 2639-2654. https://doi.org/10.1007/s00204-022-03337-8
Tan, B.L., Norhaizan, M.E., Huynh, K., Yeap, S.K., Hazilawati, H. and Roselina, K., 2015. Brewers’ rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats. World Journal of Gastroenterology 21: 8826-8835. https://doi.org/10.3748/wjg.v21.i29.8826
Tang, S., Leung, J.C., Abe, K., Chan, K.W., Chan, L.Y., Chan, T.M. and Lai, K.N., 2003. Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. Journal of Clinical Investigation 111: 515-527. https://doi.org/10.1172/jci16079
Uber, A.M. and Sutherland, S.M., 2020. Nephrotoxins and nephrotoxic acute kidney injury. Pediatric Nephrology 35: 1825-1833. https://doi.org/10.1007/s00467-019-04397-2
Van Le Thanh, B., Lemay, M., Bastien, A., Lapointe, J., Lessard, M., Chorfi, Y. and Guay, F., 2016. The potential effects of antioxidant feed additives in mitigating the adverse effects of corn naturally contaminated with Fusarium mycotoxins on antioxidant systems in the intestinal mucosa, plasma, and liver in weaned pigs. Mycotoxin Research 32: 99-116. https://doi.org/10.1007/s12550-016-0245-y
Wang, L., Wang, Y., Shao, H., Luo, X., Wang, R., Li, Y., Li, Y., Luo, Y., Zhang, D. and Chen, Z., 2017. In vivo toxicity assessment of deoxynivalenol-contaminated wheat after ozone degradation. Food Additives and Contaminants Part A 34: 103-112. https://doi.org/10.1080/19440049.2016.1253112
Wasung, M.E., Chawla, L.S. and Madero, M., 2015. Biomarkers of renal function, which and when? Clinica Chimica Acta 438: 350-357. https://doi.org/10.1016/j.cca.2014.08.039
Watanuki, H., Ota, K., Tassakka, A.C.M.A.R., Kato, T. and Sakai, M., 2006. Immunostimulant effects of dietary Spirulina platensis on carp, Cyprinus carpio. Aquaculture 258: 157-163. https://doi.org/10.1016/j.aquaculture.2006.05.003
Wellington, M.O., Bosompem, M.A., Petracek, R., Nagl, V. and Columbus, D.A., 2020. Effect of long-term feeding of graded levels of deoxynivalenol (DON) on growth performance, nutrient utilization, and organ health in finishing pigs and DON content in biological samples. Journal of Animal Science 98. https://doi.org/10.1093/jas/skaa378
Wright, R.D. and Beresford, M.W., 2018. Podocytes contribute, and respond, to the inflammatory environment in lupus nephritis. American Journal of Physiology – Renal Physiology 315: F1683-F1694. https://doi.org/10.1152/ajprenal.00512.2017
Zhang, W., Zhang, S., Zhang, M., Yang, L., Cheng, B., Li, J. and Shan, A., 2018. Individual and combined effects of Fusarium toxins on apoptosis in PK15 cells and the protective role of N-acetylcysteine. Food and Chemical Toxicology 111: 27-43. https://doi.org/10.1016/j.fct.2017.10.057
Zhang, X., Chen, X., Song, H., Chen, H.Z. and Rovin, B.H., 2005. Activation of the Nrf2/antioxidant response pathway increases IL-8 expression. European Journal of Immunology 35: 3258-3267. https://doi.org/10.1002/eji.200526116
Zhao, L., Li, X., Ji, C., Rong, X., Liu, S., Zhang, J. and Ma, Q., 2016. Protective effect of Devosia sp. ANSB714 on growth performance, serum chemistry, immunity function and residues in kidneys of mice exposed to deoxynivalenol. Food and Chemical Toxicology 92: 143-149. https://doi.org/10.1016/j.fct.2016.03.020
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 441 | 86 | 23 |
| Full Text Views | 17 | 3 | 1 |
| PDF Views & Downloads | 38 | 6 | 0 |
Deoxynivalenol (DON) is a mycotoxin that frequently contaminates food crops and negatively impacts human and animal health. While inositol-6-phosphate (IP6) is known to counteract DON-induced intestinal damage, inflammation, and oxidative stress, its ability to alleviate DON-caused kidney injury is yet unexplored. This study assessed DON’s kidney effects and IP6’s protective capability using an ex vivo renal explants model. From 360 explants taken from six pigs, four groups were formed: control (culture medium), DON (10 μM equivalent to 3 mg/kg of feed), IP6 group (5 mM), and DON + IP6 (10 μM + 5 mM). DON elevated creatinine levels and γ-glutamyl transferase activity in the culture medium. It led to cytoplasmic vacuolation in convoluted tubular epithelial cells and tubular necrosis, a drop in antioxidant potential (ABTS) and a rise in interleukin (IL)-8 mRNA. The introduction of IP6 restored renal histological and functional parameters, bolstered antioxidant status, enhanced IL-10 gene expression, and reduced superoxide anion levels. These results indicate that within the model of renal explants, IP6 significantly alleviates the nephrotoxic effects of DON while efficiently regulating the antioxidative and anti-inflammatory response within the kidneys.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 441 | 86 | 23 |
| Full Text Views | 17 | 3 | 1 |
| PDF Views & Downloads | 38 | 6 | 0 |