In this paper, the potential antidote efficacy of commercially available formulations of various feed additives such as Minazel-Plus®, Mycosorb®, and Mycofix® was considered by recording their incidence on general health, body weight, and food and water intake, as well as through histopathology and semiquantitative analysis of gastric alterations in Wistar rats treated with the T-2 toxin in a single-dose regimen of 1.67 mg/kg p.o. (1 LD50) for 4 weeks. As an organic adsorbent, Mycosorb® successfully antagonized acute lethal incidence of the T-2 toxin (protective index (PI) = 2.25; p < 0.05 vs. T-2 toxin), and had adverse effects on body weight gain as well as food and water intake during the research (p < 0.001). However, the protective efficacy of the other two food additives was significantly lower (p < 0.05). Treatment with Mycosorb® significantly reduced the severity of gastric damage, which was not the case when the other two adsorbents were used. Our results suggest that Mycosorb® is a much better adsorbent for preventing the adverse impact of the T-2 toxin as well as its toxic metabolites compared with Minazel-plus® or Mycofix-plus®, and it almost completely suppresses its acute toxic effects and cytotoxic potential on the gastric epithelial, glandular, and vascular endothelial cells.

College of Life Science Yangtze University Jingzhou Hubei 434023 China

Department for Experimental Toxicology and Pharmacology National Poison Control Centre Military Medical Academy 11000 Belgrade Serbia

Department for Physiology Faculty of Veterinary Medicine University of Belgrade 11000 Belgrade Serbia

Department of Analytical Chemistry Faculty of Chemistry University of Belgrade 11158 Belgrade Serbia

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanského 62 500 03 Hradec Králové Czech Republic

Department of Pharmacological Science Medical Faculty of the Military Medical Academy University of Defence 11000 Belgrade Serbia

Institute for Poultry Disease Faculty of Veterinary Medicine University of Belgrade 11000 Belgrade Serbia

Special Police Unit Police Department of the City of Belgrade Ministry of Interior 11030 Belgrade Serbia

Zobrazit více v PubMed

Marin S., Ramos A.J., Cano-Sancho G., Sanchis V. Mycotoxins: Occurrence, toxicology, and exposure assessment. Food Chem. Toxicol. 2013;60:218–237. doi: 10.1016/j.fct.2013.07.047. PubMed DOI

Grenier B., Applegate T.J. Modulation of intestinal function following mycotoxin ingestion: Meta-analysis of published experiments in animals. Toxins. 2013;5:396–430. doi: 10.3390/toxins5020396. PubMed DOI PMC

Koch P. State of art of trichothecenes analysis. Toxicol. Lett. 2004;153:109–112. doi: 10.1016/j.toxlet.2004.04.027. PubMed DOI

Li Y., Wang Z., Beier R.C., Shen J., de Smet D., de Saeger S., Zhang S. T-2 Toxin, a trichothecene mycotoxin: Review of toxicity, metabolism, and analytical methods. J. Agric. Food Chem. 2011;59:3441–3453. doi: 10.1021/jf200767q. PubMed DOI

Sudakin D.L. Trichothecenes in the environment: Relevance to human health. Toxicol. Lett. 2003;143:97–107. doi: 10.1016/S0378-4274(03)00116-4. PubMed DOI

Richard J.L. Some major mycotoxins and their mycotoxicoses—An overview. Int. J. Food Microbiol. 2007;119:3–10. doi: 10.1016/j.ijfoodmicro.2007.07.019. PubMed DOI

Abbas H.K., Yoshizawa T., Shier W.T. Cytotoxicity and phytotoxicity of trichothecene mycotoxins produced by Fusarium spp. Toxicon. 2013;74:68–75. doi: 10.1016/j.toxicon.2013.07.026. PubMed DOI

Jaćević V. Therapy of Acute Poisoning by T-2 Toxin. 1st ed. Andrejevic Foundation; Belgrade, Serbia: 2006. pp. 1–80.

Jaćević V., Kuca K., Milovanovic Z., Bocarov-Stancic A., Rancic I., Bokonjic D., Dragojevic-Simic V., Segrt Z. Gastroprotective effects of amifostine in rats treated by T-2 toxin. Tox. Rev. 2018;3:123–127. doi: 10.1080/15569543.2017.1329211. DOI

Speijers G., Speijers M. Combined toxic effects of mycotoxins. Toxicol. Lett. 2004;153:91–98. doi: 10.1016/j.toxlet.2004.04.046. PubMed DOI

Bennett J.W., Klich M. Mycotoxins. Clin. Microbiol. Rev. 2003;16:497–516. doi: 10.1128/CMR.16.3.497-516.2003. PubMed DOI PMC

Wu Q., Dohnal V., Kuča K., Yuanet Z. Trichothecenes: Structure-toxic activity relationships. Curr. Drug Metab. 2013;14:641–660. doi: 10.2174/1389200211314060002. PubMed DOI

Resanović R.M., Nešić K.D., Nešić V.D., Palić T.D., Jaćević V.M. Mycotoxins in poultry production. Proc. Nat. Sci. 2009;116:7–14. doi: 10.2298/ZMSPN0916007R. DOI

Borison L.H., Goodheart L.M., Thut C.D. Hypovolemic shock in acute lethal T-2 mycotoxicosis. Toxicol. Appl. Pharmacol. 1991;108:107–113. doi: 10.1016/0041-008X(91)90273-H. PubMed DOI

Wu Q., Wang X., Yang W., Nussler A.K., Xiong L., Kuča K., Dohnal V., Zhang X., Yuan Z. Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: An update. Arch. Toxicol. 2014;88:1309–1326. doi: 10.1007/s00204-014-1280-0. PubMed DOI

Wu Q., Wang X., Nepovimova E., Miron A., Liu Q., Wang Y., Su D., Yang H., Li L., Kuča K. Trichothecenes: Immunomodulatory effects, mechanisms, and anti-cancer potential. Arch. Toxicol. 2017;91:3737–3785. doi: 10.1007/s00204-017-2118-3. PubMed DOI

Jaćević V., Wu Q., Nepovimova E., Kuča K. Efficacy of methylprednisolone on T-2 toxin-induced cardiotoxicity in vivo: A pathohistological study. Environ. Toxicol. Pharmacol. 2019;71:103221. doi: 10.1016/j.etap.2019.103221. PubMed DOI

Jaćević V., Wu Q., Nepovimova E., Kuča K. Cardiomyopathy induced by T-2 toxin in rats. Food Chem. Toxicol. 2020;137:111138. doi: 10.1016/j.fct.2020.111138. PubMed DOI

Jaćević V. Absorbents Efficacy in the Therapy of Acute T-2 Toxin Poisoning. 1st ed. Andrejevic Foundation; Belgrade, Serbia: 2006. pp. 1–126.

Jaćević V., Resanović R., Bočarov-Stančić A., Đorđević S., Dragojević-Simić V., Vukajlović A., Bokonjić D. Gastroprotective effects of novel antidotal combination in rats acutely poisoned by T-2 toxin. Acta Vet. 2010;60:461–478. doi: 10.2298/AVB1006461J. DOI

Wu Q., Engemann A., Cramer B., Welsch T., Yuan Z., Humpf H.-U. Intestinal metabolism of T-2 toxin in the pig cecum model. Mycotoxin Res. 2012;28:191–198. doi: 10.1007/s12550-012-0134-y. PubMed DOI

Bondy G., Pestka J. Immunomodulation by fungal toxins. J. Toxicol. Environ. Health B Crit. Rev. 2000;3:109–143. doi: 10.1080/109374000281113. PubMed DOI

Doi K., Uetsuka K. Mechanisms of mycotoxin-induced neurotoxicity through oxidative stress-associated pathways. Int. J. Mol. Sci. 2011;12:5213–5237. doi: 10.3390/ijms12085213. PubMed DOI PMC

Chaudhary K.R., Batchu S.N., Seubert J.M. Cytochrome P450 enzymes and the heart. IUBMB Life. 2009;61:954–960. doi: 10.1002/iub.241. PubMed DOI

Matés J.M. Erratum to ‘Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology’. Toxicology. 2000;153:83–104. doi: 10.1016/S0300-483X(00)00306-1. PubMed DOI

Ahmadinejad F., Geir Møller S., Hashemzadeh-Chaleshtori M., Bidkhori G., Jami M.S. Molecular mechanisms behind free radical scavengers’ function against oxidative stress. Antioxidants. 2017;6:51. doi: 10.3390/antiox6030051. PubMed DOI PMC

Nakagiri A., Murakami M. Roles of NADPH oxidase in the occurrence of gastric damage and expression of cyclooxygenase-2 during ischemia/reperfusion in rat stomachs. J. Pharmacol. Sci. 2009;111:352–360. doi: 10.1254/jphs.09169FP. PubMed DOI

Salim A.S. A possible new approach to the problem of refractory peptic ulceration. A role for free radical scavengers? Scott. Med. J. 1990;36:19–20. doi: 10.1177/003693309103600110. PubMed DOI

Williams P.P. Effects of T-2 mycotoxin on gastrointestinal tissues: A review of in vivo and in vitro models. Arch. Environ. Contam. Toxicol. 1989;18:374–387. doi: 10.1007/BF01062362. PubMed DOI PMC

Mackei M., Orbán K., Molnár A., Pál L., Dublecz K., Husvéth F., Neogrády Z., Mátis G. Cellular effects of T-2 toxin on primary hepatic cell culture models of chickens. Toxins. 2020;12:46. doi: 10.3390/toxins12010046. PubMed DOI PMC

Yang S., Li Y., Cao X., Hu D., Wang Z., Wang Y., Shen J., Zhang S. Metabolic pathways of T-2 toxin in vivo and in vitro systems of Wistar rats. J. Agric. Food Chem. 2013;61:9734–9743. doi: 10.1021/jf4012054. PubMed DOI

Kalantari H., Moosavi M. Review on T-2 toxin. Jundish. J. Nat. Pharmaceut. Prod. 2010;5:26–38.

Huang Z., Wang Y., Qiu M., Sun L., Deng Y., Wang X., Bi S., Gooneratne R., Zhao J. Effects of T-2 toxin on digestive enzyme activity, intestinal histopathology and growth in shrimp Litopenaeus vannamei. Sci. Rep. 2019;9:13175. doi: 10.1038/s41598-019-49004-4. PubMed DOI PMC

Nayakwadi S., Ramu R., Kumar Sharma A.K., Gupta V., Rajukumar K., Kumar V., Shirahatti P.S., Rashmi L., Basalingappa K.M. Toxicopathological studies on the effects of T-2 mycotoxin and their interaction in juvenile goats. PLoS ONE. 2020;15:e0229463. doi: 10.1371/journal.pone.0229463. PubMed DOI PMC

Garcia A.R., Avila E., Rosiles R., Petrone V.M. Evaluation of two mycotoxin binders to reduce the toxicity of broiler diets containing ochratoxin A and T-2 toxin contaminated grain. Avian Dis. 2003;47:691–699. doi: 10.1637/7021. PubMed DOI

Daković A., Kragović M., Rottinghaus G.E., Ledoux D.R., Butkeraitis P., Vojislavljević D.Z., Zarić S.D., Stamenić L. Preparation and characterization of zinc-exchanged montmorillonite and its effectiveness as aflatoxin B1 adsorbent. Mat. Chem. Phys. 2012;137:213–220. doi: 10.1016/j.matchemphys.2012.09.010. DOI

Nedeljković-Trailović J., Stefanović S., Trailovic S. In vitro investigation three different adsorbents against ochratoxin A in broilers. Br. Poult. Sci. 2013;54:515–523. doi: 10.1080/00071668.2013.798627. PubMed DOI

Nedeljković-Trailović J., Trailović S., Resanović R., Milićević D., Jovanovic M., Vasiljevic M. Comparative investigation of the efficacy of three different adsorbents against OTA-induced toxicity in broiler chickens. Toxins. 2015;7:1174–1191. doi: 10.3390/toxins7041174. PubMed DOI PMC

Maisanaba S., Pichardo S., Puerto M., Gutiérrez-Praena D., Cameán A.M., Jos A. Toxicological evaluation of clay minerals and derived nanocomposites. Environ. Res. 2015;138:233–254. doi: 10.1016/j.envres.2014.12.024. PubMed DOI

Marković M., Daković A., Rottinghaus G.E., Petković A., Kragović M., Krajišnik D., Milić J. Ochratoxin A and zearalenone adsorption by the natural zeolite treated with benzalkonium chloride. Colloids Surfaces A. 2017;529:7–17. doi: 10.1016/j.colsurfa.2017.05.054. DOI

Jaćević V.M., Bočarov-Stančić A., Resanović R.D., Đorđević S., Bokonjić D., Stojiljković M.P. Basic mechanisms of the cellular alterations in T-2 toxin poisoning: Influence on the choice and result of the therapy. Proc. Nat. Sci. 2007;113:45–53.

Nešić K., Resanović R., Jakić-Dimić D., Nešić V. Efficiency of various feed additives on the performance of broilers treated with T-2 toxin. Biotech. Anim. Husban. 2011;27:705–711. doi: 10.2298/BAH1103705N. DOI

Liu D., Wu Q., Liu H., Lu C., Gu C., Kuča K., Wu W. Effects of montmorillonite on growth performance, serum biochemistry and oxidative stress of red-crowned crane (Grus japonensis) fed mycotoxin-contaminated feed. Curr. Drug Metab. 2020;21:1. doi: 10.2174/1389200221666200726221126. PubMed DOI

Diaz G.J., Cortes A., Roldan L. Evaluation of the efficacy of four feed additives against the adverse effects of T-2 toxin in growing broiler chickens. J. Appl. Poult. Res. 2005;14:226–231. doi: 10.1093/japr/14.2.226. DOI

Jaćević V., Lazarević M., Vukajlović A., Bočarov-Stančić A., Resanović R., Điorđević S. Antidotal efficacy of various adsorbents in rats acutely poisoned with T-2 toxin: A comparative evaluation; Proceedings of the Alltech’s 25rd International Symposium—Science and Technology in the Feed Industry; Lexington, KY, USA. 17–20 May 2009; p. 708.

Yazar S., Omurtag G.Z. Fumonisins, trichothecenes and zearalenone in cereals. J. Mol. Sci. 2008;9:2062–2090. doi: 10.3390/ijms9112062. PubMed DOI PMC

Wu Q., Dohnal V., Huang L., Kuca K., Yuan Z. Metabolic pathways of trichothecenes. Drug Metab. Rev. 2010;42:250–267. doi: 10.3109/03602530903125807. PubMed DOI

Gallo A., Giuberti G., Frisvad J.C., Bertuzzi T., Nielsen K.F. Review on mycotoxin issues in ruminants: Occurrence in forages, effects of mycotoxin ingestion on health status and animal performance and practical strategies to counteract their negative effects. Toxins. 2015;7:3057–3111. doi: 10.3390/toxins7083057. PubMed DOI PMC

Yiannikouris A., Jouany J.P. Mycotoxins in feeds and their fate in animals: A review. Anim. Res. 2002;51:81–99. doi: 10.1051/animres:2002012. DOI

Friend S.C., Hancock D.S., Schiefer H.B., Babiuk L.A. Experimental T-2 toxicosis in sheep. Can. J. Comp. Med. 1983;47:291–297. PubMed PMC

Quiroga M.A., Miguel A.R., Carlos J.P. T-2 mycotoxin intoxication in piglets: A systematic pathological approach and apoptotic immune-histochemical studies. Braz. J. Vet. Pathol. 2009;2:16–22.

Wang L., Fitzpatrick D.W., Wilson J.R. Effect of dietary T-2 toxin on biogenic monoamines in discrete areas of the rat brain. Food Chem. Toxicol. 1993;31:191–197. doi: 10.1016/0278-6915(93)90093-E. PubMed DOI

Huszenicza G., Fekete S., Szigeti G., Kulcsár M., Kellems R.O., Nagy P., Cseh S., Veresegyházy T., Huilár I. Ovarian consequences of low dose peroral fusarium (T-2) toxin in a ewe and heifer model. Theriogenology. 2000;53:1631–1639. doi: 10.1016/S0093-691X(00)00303-4. PubMed DOI

Ferreras M.C., Benavides J., Garcia-Pariente C., Delgado L., Fuertes M., Munoz M., García-Marín J.F., Pérez V. Acute and chronic disease associated with naturally occurring T-2 mycotoxicosis in sheep. J. Comp. Pathol. 2013;148:236–242. doi: 10.1016/j.jcpa.2012.05.016. PubMed DOI

Kemboi D.C., Antonissen G., Ochieng P.E., Croubels S., Okoth S., Kangethe E.K., Faas J., Lindahl J.F., Gathumbi J.K. A review of the impact of mycotoxins on dairy cattle health: Challenges for food safety and dairy production in sub-Saharan Africa. Toxins. 2020;12:222. doi: 10.3390/toxins12040222. PubMed DOI PMC

Yiannikouris A., Jouany J.P., Bertin G. Counteracting mycotoxin contamination: The effectiveness of Saccharomyces cerevisiae cell wall glucans in Mycosorb® for sequestering mycotoxins; Proceedings of the Alltech’s 23rd Annual Symposium; Stamford, UK. 28–29 June 2007; p. 15.

Kubena L.F., Harvey R.B., Huff W.E., Corrier D.E., Phillips T.D., Rottinghaus G.E. Efficacy of a hydrated sodium calcium aluminosilicate to reduce the toxicity of aflatoxin and T-2 toxin. Poult. Sci. 1990;69:1078–1086. doi: 10.3382/ps.0691078. PubMed DOI

Kubena L.F., Harvey R.B., Huff W.E., Elissalde M.H., Yersin A.G., Phillips D.E., Rottinghaus G.E. Efficacy of a hydrated sodium calcium aluminosilicate to reduce the toxicity of aflatoxin and diacetoxyscirpenol. Poult. Sci. 1993;72:51–59. doi: 10.3382/ps.0720051. PubMed DOI

Phillips T.D. Dietary clay in the chemoprevention of aflatoxin-induced disease. Toxicol. Sci. 1999;52:118–126. doi: 10.1093/toxsci/52.suppl_1.118. PubMed DOI

Fuchs E., Binder E.M., Heidler D., Krska R. Structural characterization of metabolites after the microbial degradation of type A trichothecenes by the bacterial strain BBSH 797. Food Addit. Contam. 2002;19:379–386. doi: 10.1080/02652030110091154. PubMed DOI

Dvorska J.E., Surai P.F. Effects of T-2 Toxin, zeolite and Mycosorb on antioxidant systems of growing quail. Asian Australas. J. Anim. Sci. 2001;14:1752–1757. doi: 10.5713/ajas.2001.1752. DOI

Dvorska J.E., Surai P.F., Speake B.K., Sparks N.H. Protective effect of modified glucomannans against aurofusarin-induced changes in quail egg and embryo. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2003;135C:337–343. doi: 10.1016/S1532-0456(03)00122-4. PubMed DOI

Swamy H.V.L.N., Smith T.K., Cotter P.F., Boermans H.J., Sefton A.E. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on production and metabolism in broilers. Poult. Sci. 2002;81:966–975. doi: 10.1093/ps/81.7.966. PubMed DOI

Swamy H.V.L.N., Smith T.K., MacDonald E.J., Boermans H.J., Squires E.J. Effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on swine performance, brain regional neurochemistry, and serum chemistry and the efficacy of a polymeric glucomannan mycotoxin adsorbent. J. Anim. Sci. 2002;80:3257–3267. doi: 10.2527/2002.80123257x. PubMed DOI

Jamalludin M., Wang S., Boldogh I., Tian B., Brasier A.R. (2007). TNF-alpha-induced NFkappaB/RelA Ser (276) phosphorylation and enhanceosome formation is mediated by a ROS-dependent PKAc pathway. Cell Signal. 2007;19:1419–1433. doi: 10.1016/j.cellsig.2007.01.020. PubMed DOI

Babbar N., Casero R.A. Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: A potential mechanism for inflammation-induced carcinogenesis. Cancer Res. 2006;66:11125–11130. doi: 10.1158/0008-5472.CAN-06-3174. PubMed DOI

Bočarov-Stančić A., Jaćević V., Resanović R., Bjelić M. Optimization of laboratory conditions for the biosynthesis of type trichothecenes proc. Proc. Nat. Sci. 2007;113:35–44.

Bočarov-Stančić A., Lević J.T., Dimić G.R., Stanković S.Ž., Salma N.M. Investigation of the toxigenic potential of fungal species by the use of a simple screening method. Proc. Nat. Sci. Matica Srpska Novi Sad. 2009;116:25–32. doi: 10.2298/ZMSPN0916025B. DOI

Bočarov-Stančić A., Salma N.M., Pantić V.R., Adamović M.J., Miljković A.D., Suzić S.V. Microbiological and mycotoxicological correctness of protein feed ingredients in Vojvodina. Proc. Nat. Sci. Matica Srpska Novi Sad. 2011;120:211–218. doi: 10.2298/ZMSPN1120213B. DOI

Litchfield J., Wilcoxon F. A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther. 1949;96:99–113. PubMed

Jaćević V., Jovic D., Kuča K., Dragojevic-Simic V., Dobric S., Trajkovic S., Borisev I., Segrt Z., Milovanovic Z., Bokonjic D., et al. Effects of Fullerenol nanoparticles and Amifostine on radiation-induced tissue damages: Histopathological analysis. J. Appl. Biomed. 2016;14:285–297. doi: 10.1016/j.jab.2016.05.004. DOI

Jaćević V., Djordjevic A., Srdjenovic B., Milic-Tores V., Segrt Z., Dragojevic-Simic V., Kuca K. Fullerenol nanoparticles prevent doxorubicin-induced acute hepatotoxicity in rats. Exp. Mol. Pathol. 2017;102:360–369. doi: 10.1016/j.yexmp.2017.03.005. PubMed DOI

Jaćević V., Dragojević-Simić V., Tatomirović Ž., Dobrić S., Bokonjić D., Kovačević A., Nepovimova E., Vališ M., Kuča K. The efficacy of amifostine against multiple-dose doxorubicin-induced toxicity in rats. Int. J. Mol. Sci. 2018;19:2370. doi: 10.3390/ijms19082370. PubMed DOI PMC

Jaćević V., Nepovimova E., Kuča K. Toxic injury to the muscle tissue of rats following acute oximes exposure. Sci. Rep. 2019;9:1457. doi: 10.1038/s41598-018-37837-4. PubMed DOI PMC

Nežić L., Škrbić R., Amidžić L., Gajanin R., Kuča K., Jaćević V. Simvastatin protects cardiomyocytes against endotoxin-induced apoptosis and up-regulates survivin/NF-κB/p65 expression. Sci. Rep. 2018;8:14652. doi: 10.1038/s41598-018-32376-4. PubMed DOI PMC

Nežić L., Amidžić L., Škrbić R., Gajanin R., Nepovimova E., Vališ M., Kuča K., Jaćević V. Simvastatin inhibits endotoxin-induced apoptosis in liver and spleen through up-regulation of survivin/NF-kB/p65 expression. Front. Pharmacol. 2019;10:54. doi: 10.3389/fphar.2019.00054. PubMed DOI PMC

Jaćević V., Nepovimova E., Kuča K. Acute toxic injuries of rat’s visceral tissues induced by different oximes. Sci. Rep. 2019;9:16425. doi: 10.1038/s41598-019-52768-4. PubMed DOI PMC

Aflatoxin Detoxification Using Microorganisms and Enzymes