Proteomic Changes in the Cytoplasmatic Fraction of Weaned Piglets Liver and Kidney Under Antioxidants and Mycotoxins Diets

Mycotoxin contamination represents a threat for human and animal health. Antioxidants can mitigate some of these effects due to their ability to scavenge free radicals, reduce oxidative stress, and have anti-inflammatory and immunomodulatory properties. This work investigates the potential of antioxidants derived from grape seed and sea buckthorn to mitigate the adverse effects of aflatoxin B1 (AFB1) and ochratoxin A (OTA), as mycotoxins contamination in weaned piglet diets. We used an unbiased Data Independent Acquisition (DIA) approach to analyse the proteomic impact of OTA and AFB1-contaminated diets on liver and kidney cytoplasmic metabolism, particularly focusing on the conjugation phase. We show that some of the mycotoxins effects are partial mitigated by the antioxidants enriched diet. Additionally, in kidneys, some of the effects are synergistically amplified, such as proteins involved in the fatty acids degradation, peroxisome, PPAR signalling, translation, TCA cycle and the excretion pathways. Inclusion of antioxidants in the animal diet can have beneficial effects. Nevertheless, caution is advised, synergistic effects can occur with potentially more serious consequences than the effect of mycotoxins alone.

[1]  J. Hengstler,et al.  Comparative metabolism of aflatoxin B1 in mouse, rat and human primary hepatocytes using HPLC–MS/MS , 2023, Archives of Toxicology.

[2]  J. Sharifi‐Rad,et al.  Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases , 2023, Frontiers in Chemistry.

[3]  Abhishek Kumar,et al.  Fungal mycotoxins in food commodities: present status and future concerns , 2023, Frontiers in Sustainable Food Systems.

[4]  A. Dinischiotu,et al.  Natural Antioxidant By-Product Mixture Counteracts the Effects of Aflatoxin B1 and Ochratoxin A Exposure of Piglets after Weaning: A Proteomic Survey on Liver Microsomal Fraction , 2023, Toxins.

[5]  C. Borda,et al.  Effects of Plant-Based Antioxidants in Animal Diets and Meat Products: A Review , 2023, Foods.

[6]  J. Simal-Gándara,et al.  A review of recent innovative strategies for controlling mycotoxins in foods , 2022, Food Control.

[7]  J. Lorenzo,et al.  Plant by-product antioxidants: Control of protein-lipid oxidation in meat and meat products , 2022, LWT.

[8]  A. Kurtz,et al.  Flexible and multifaceted: the plasticity of renin-expressing cells , 2022, Pflügers Archiv - European Journal of Physiology.

[9]  G. Feijoo,et al.  Exploring the potential of antioxidants from fruits and vegetables and strategies for their recovery , 2022, Innovative Food Science & Emerging Technologies.

[10]  A. Brazma,et al.  The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences , 2021, Nucleic Acids Res..

[11]  A. Dinischiotu,et al.  The Reduction of the Combined Effects of Aflatoxin and Ochratoxin A in Piglet Livers and Kidneys by Dietary Antioxidants , 2021, Toxins.

[12]  J. Redón,et al.  Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney , 2021, International journal of molecular sciences.

[13]  J. Rueff,et al.  The Central Role of Cytochrome P450 in Xenobiotic Metabolism—A Brief Review on a Fascinating Enzyme Family , 2021, Journal of xenobiotics.

[14]  Michael K. Wendt,et al.  Pyruvate carboxylase and cancer progression , 2021, Cancer & metabolism.

[15]  A. Dinischiotu,et al.  The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A , 2021, Toxins.

[16]  Shuwen Liu,et al.  Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-κB and JAK-STAT Signaling Pathways , 2021, Journal of Virology.

[17]  Riana R. Pryor,et al.  Kidney physiology and pathophysiology during heat stress and the modification by exercise, dehydration, heat acclimation and aging , 2020, Temperature.

[18]  T. Webster,et al.  A Review on the Biodistribution, Pharmacokinetics and Toxicity of Bismuth-Based Nanomaterials , 2020, International journal of nanomedicine.

[19]  Zhiqiang Shen,et al.  Mycotoxin contamination and control strategy in human, domestic animal and poultry: A review. , 2020, Microbial pathogenesis.

[20]  S Joshua Swamidass,et al.  The Metabolic Rainbow: Deep Learning Phase I Metabolism in Five Colors , 2020, J. Chem. Inf. Model..

[21]  Donato Greco,et al.  Decontamination of Mycotoxin-Contaminated Feedstuffs and Compound Feed , 2019, Toxins.

[22]  Z. Zuo,et al.  Current trends in drug metabolism and pharmacokinetics , 2019, Acta pharmaceutica Sinica. B.

[23]  Christoph B. Messner,et al.  DIA-NN: Neural networks and interference correction enable deep proteome coverage in high throughput , 2019, Nature Methods.

[24]  Osman Ugur Sezerman,et al.  pathfindR: An R Package for Comprehensive Identification of Enriched Pathways in Omics Data Through Active Subnetworks , 2019, Front. Genet..

[25]  Perry G. Ridge,et al.  RAB10: an Alzheimer’s disease resilience locus and potential drug target , 2018, Clinical interventions in aging.

[26]  E. Ferrer,et al.  Presence of mycotoxins in ready-to-eat food and subsequent risk assessment. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  F. Merolla,et al.  CCDC6: the identity of a protein known to be partner in fusion , 2018, International journal of cancer.

[28]  E. Fearon,et al.  Thiosulfate sulfurtransferase-like domain–containing 1 protein interacts with thioredoxin , 2018, The Journal of Biological Chemistry.

[29]  O. Babalola,et al.  Prevalence of Mycotoxins and Their Consequences on Human Health , 2018, Toxicological research.

[30]  S. Basu,et al.  Glucuronidation: driving factors and their impact on glucuronide disposition , 2017, Drug metabolism reviews.

[31]  S. Croubels,et al.  Impact of Fusarium mycotoxins on hepatic and intestinal mRNA expression of cytochrome P450 enzymes and drug transporters, and on the pharmacokinetics of oral enrofloxacin in broiler chickens. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[32]  E. Heiss,et al.  Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins altertoxin I and II , 2016, Archives of Toxicology.

[33]  D. Landsman,et al.  HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells , 2016, Nucleic acids research.

[34]  F. Guay,et al.  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 , 2016, Mycotoxin Research.

[35]  P. Álvarez,et al.  Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results , 2015, Oxidative medicine and cellular longevity.

[36]  A. Collier,et al.  The Development of UDP-Glucuronosyltransferases 1A1 and 1A6 in the Pediatric Liver , 2011, Drug Metabolism and Disposition.

[37]  Krishna R. Kalari,et al.  Betaine-homocysteine methyltransferase: human liver genotype-phenotype correlation. , 2011, Molecular genetics and metabolism.

[38]  C. Brocker,et al.  Evolutionary divergence and functions of the human acyl-CoA thioesterase gene (ACOT) family , 2010, Human Genomics.

[39]  Magnus Bergkvist,et al.  Paradoxical glomerular filtration of carbon nanotubes , 2010, Proceedings of the National Academy of Sciences.

[40]  I. Rayment,et al.  Structure, mechanism and regulation of pyruvate carboxylase. , 2008, The Biochemical journal.

[41]  W. Haschek,et al.  Fumonisin B(1) is hepatotoxic and nephrotoxic in milk-fed calves. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[42]  F. G. Young Enzymes , 1951 .

[43]  Pereira,et al.  Prevalence of , 2021 .

[44]  O. Jensen,et al.  Robust statistical testing of proteomics data with missing values improves detection of biologically relevant features , 2020 .

[45]  S. Kaur,et al.  Cells , 2019, Tissue Engineering in Oral and Maxillofacial Surgery.