Skip to main content
Log in

Curcumin alleviates AFB1-induced nephrotoxicity in ducks: regulating mitochondrial oxidative stress, ferritinophagy, and ferroptosis

  • Original Article
  • Published:
Mycotoxin Research Aims and scope Submit manuscript

Abstract

Aflatoxin B1 (AFB1), an extremely toxic mycotoxin that extensively contaminates feed and food worldwide, poses a major hazard to poultry and human health. Curcumin, a polyphenol derived from turmeric, has attracted great attention due to its wonderful antioxidant properties. Nevertheless, effects of curcumin on the kidneys of ducks exposed to AFB1 remain unclear. Additionally, the underlying mechanism between AFB1 and ferroptosis (based on excessive lipid peroxidation) has not been sufficiently elucidated. This study aimed to investigate the protective effects and potential mechanisms of curcumin against AFB1-induced nephrotoxicity in ducklings. The results indicated that curcumin alleviated AFB1-induced growth retardation and renal distorted structure in ducklings. Concurrently, curcumin inhibited AFB1-induced mitochondrial-mediated oxidative stress by reducing the expression levels of oxidative damage markers malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG) and improved the expression of mitochondria-related antioxidant enzymes and the Nrf2 pathway. Notably, curcumin attenuated iron accumulation in the kidney, inhibited ferritinophagy via the NCOA4 pathway, and balanced iron homeostasis, thereby alleviating AFB1-induced ferroptosis in the kidney. Collectively, our results suggest that curcumin alleviates AFB1-induced nephrotoxicity in ducks by inhibiting mitochondrial-mediated oxidative stress, ferritinophagy, and ferroptosis and provide new evidence for the mechanism of AFB1-induced nephrotoxicity in ducklings treated with curcumin.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Adedara IA, Owumi SE (2023) Neurobehavioral and biochemical responses to artemisinin-based drug and aflatoxin B(1) co-exposure in rats. Mycotoxin Res 39:67–80

    Article  CAS  PubMed  Google Scholar 

  • ALTamimi JZ, AlFaris NA, Al-Farga AM, Alshammari GM, BinMowyna MN, Yahya MA (2021) Curcumin reverses diabetic nephropathy in streptozotocin-induced diabetes in rats by inhibition of PKCbeta/p(66)Shc axis and activation of FOXO-3a. J Nutr Biochem 87:108515

  • Bayir H, Dixon SJ, Tyurina YY, Kellum JA, Kagan VE (2023) Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol 19:315–336

    Article  CAS  PubMed  Google Scholar 

  • Benkerroum N (2020) Chronic and acute toxicities of aflatoxins: mechanisms of action. Int J Environ Res Public Health 17

  • Bernabe-Pineda M, Ramirez-Silva MT, Romero-Romo MA, Gonzalez-Vergara E, Rojas-Hernandez A (2004) Spectrophotometric and electrochemical determination of the formation constants of the complexes curcumin-Fe(III)-water and curcumin-Fe(II)-water. Spectrochim Acta A Mol Biomol Spectrosc 60:1105–1113

    Article  PubMed  Google Scholar 

  • Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575:688–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen GH, Song CC, Pantopoulos K, Wei XL, Zheng H, Luo Z (2022) Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway. Free Radical Biol Med 180:95–107

    Article  CAS  Google Scholar 

  • Chen X, Li J, Kang R, Klionsky DJ, Tang D (2021) Ferroptosis: machinery and regulation. Autophagy 17:2054–2081

    Article  CAS  PubMed  Google Scholar 

  • Chuaysrinule C, Maneeboon T, Mahakarnchanakul W (2023) Mutual effects on mycotoxin production during co-culture of ochratoxigenic and aflatoxigenic Aspergillus strains. Mycotoxin Res 39:57–66

    Article  CAS  PubMed  Google Scholar 

  • Dard L, Blanchard W, Hubert C, Lacombe D, Rossignol R (2020) Mitochondrial functions and rare diseases. Mol Aspects Med 71:100842

    Article  CAS  PubMed  Google Scholar 

  • Deng D, Tang J, Liu Z, Tian Z, Song M, Cui Y, Rong T, Lu H, Yu M, Li J, Pang R, Ma X (2022) Functional characterization and whole-genome analysis of an aflatoxin-degrading Rhodococcus pyridinivorans strain. Biology-Basel 11.

  • Diaz GJ, Murcia HW (2019) An unusually high production of hepatic aflatoxin B1-dihydrodiol, the possible explanation for the high susceptibility of ducks to aflatoxin B1. Sci Rep 9:8010

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Paola D, D'Amico R, Genovese T, Siracusa R, Cordaro M, Crupi R, Peritore AF, Gugliandolo E, Interdonato L, Impellizzeri D, Fusco R, Cuzzocrea S, Di Paola R (2022) Chronic exposure to vinclozolin induced fibrosis, mitochondrial dysfunction, oxidative stress, and apoptosis in mice kidney. Int J Mol Sci 23

  • Doll S, Freitas FP, Shah R, Aldrovandi M, Da SM, Ingold I, Goya GA, Xavier DST, Panzilius E, Scheel CH, Mourao A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O’Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli J, Conrad M (2019) FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575:693–698

    Article  CAS  PubMed  Google Scholar 

  • Fan RF, Tang KK, Wang ZY, Wang L (2021a) Persistent activation of Nrf2 promotes a vicious cycle of oxidative stress and autophagy inhibition in cadmium-induced kidney injury. Toxicology 464:152999

    Article  CAS  PubMed  Google Scholar 

  • Fan T, Xie Y, Ma W (2021b) Research progress on the protection and detoxification of phytochemicals against aflatoxin B1-induced liver toxicity. Toxicon 195:58–68

    Article  CAS  PubMed  Google Scholar 

  • Fang X, Wang H, Han D, Xie E, Yang X, Wei J, Gu S, Gao F, Zhu N, Yin X, Cheng Q, Zhang P, Dai W, Chen J, Yang F, Yang HT, Linkermann A, Gu W, Min J, Wang F (2019) Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA 116:2672–2680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang Y, Chen X, Tan Q, Zhou H, Xu J, Gu Q (2021) Inhibiting ferroptosis through disrupting the NCOA4-FTH1 interaction: a new mechanism of action. ACS Cent Sci 7:980–989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fouche T, Claassens S, Maboeta M (2020) Aflatoxins in the soil ecosystem: an overview of its occurrence, fate, effects and future perspectives. Mycotoxin Res 36:303–309

    Article  CAS  PubMed  Google Scholar 

  • Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, Jiang X (2019) Role of mitochondria in ferroptosis. Mol Cell 73:354–363

    Article  CAS  PubMed  Google Scholar 

  • Gong Y, Hounsa A, Egal S, Turner PC, Sutcliffe AE, Hall AJ, Cardwell K, Wild CP (2004) Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa. Environ Health Perspect 112:1334–1338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gruber-Dorninger C, Jenkins T, Schatzmayr G (2019) Global mycotoxin occurrence in feed: a ten-year survey. Toxins 11

  • Guerrero-Hue M, Garcia-Caballero C, Palomino-Antolin A, Rubio-Navarro A, Vazquez-Carballo C, Herencia C, Martin-Sanchez D, Farre-Alins V, Egea J, Cannata P, Praga M, Ortiz A, Egido J, Sanz AB, Moreno JA (2019) Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis-mediated cell death. FASEB J 33:8961–8975

    Article  CAS  PubMed  Google Scholar 

  • Hassannia B, Wiernicki B, Ingold I, Qu F, Van Herck S, Tyurina YY, Bayir H, Abhari BA, Angeli J, Choi SM, Meul E, Heyninck K, Declerck K, Chirumamilla CS, Lahtela-Kakkonen M, Van Camp G, Krysko DV, Ekert PG, Fulda S, De Geest BG, Conrad M, Kagan VE, Vanden BW, Vandenabeele P, Vanden BT (2018) Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Investig 128:3341–3355

    Article  PubMed  PubMed Central  Google Scholar 

  • He J, Li Z, Xia P, Shi A, FuChen X, Zhang J, Yu P (2022) Ferroptosis and ferritinophagy in diabetes complications. Molecular Metabolism 60:101470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jallow A, Xie H, Tang X, Qi Z, Li P (2021) Worldwide aflatoxin contamination of agricultural products and foods: from occurrence to control. Comprehensive Reviews in Food Science and Food Safety 20:2332–2381

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22:266–282

    Article  PubMed  PubMed Central  Google Scholar 

  • Jing S, Lu Y, Zhang J, Ren Y, Mo Y, Liu D, Duan L, Yuan Z, Wang C, Wang Q (2022) Levistilide a induces ferroptosis by activating the Nrf2/HO-1 signaling pathway in breast cancer cells. Drug Des Devel Ther 16:2981–2993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koonyosying P, Tantiworawit A, Hantrakool S, Utama-Ang N, Cresswell M, Fucharoen S, Porter JB, Srichairatanakool S (2020) Consumption of a green tea extract-curcumin drink decreases blood urea nitrogen and redox iron in beta-thalassemia patients. Food Funct 11:932–943

    Article  CAS  PubMed  Google Scholar 

  • Li H, Li S, Yang H, Wang Y, Wang J, Zheng N (2019a) l-proline alleviates kidney injury caused by AFB1 and AFM1 through regulating excessive apoptosis of kidney cells. Toxins 11

  • Li Q, Liao J, Chen W, Zhang K, Li H, Ma F, Zhang H, Han Q, Guo J, Li Y, Hu L, Pan J, Tang Z (2022) NAC alleviative ferroptosis in diabetic nephropathy via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2/Gpx4 pathway. Free Radical Biol Med 187:158–170

    Article  CAS  Google Scholar 

  • Li S, Muhammad I, Yu H, Sun X, Zhang X (2019b) Detection of aflatoxin adducts as potential markers and the role of curcumin in alleviating AFB1-induced liver damage in chickens. Ecotoxicol Environ Saf 176:137–145

    Article  CAS  PubMed  Google Scholar 

  • Li W, Li W, Wang Y, Leng Y, Xia Z (2021) Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury. Cell Death Discovery 7:267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Song WJ, Zhang NY, Tan J, Krumm CS, Sun LH, Qi DS (2017) Biodetoxification of aflatoxin B1 in cottonseed meal by fermentation of Cellulosimicrobium funkei in duckling diet. Poult Sci 96:923–930

    Article  CAS  PubMed  Google Scholar 

  • Malir F, Pickova D, Toman J, Grosse Y, Ostry V (2023) Hazard characterisation for significant mycotoxins in food. Mycotoxin Res

  • Ma-On C, Sanpavat A, Whongsiri P, Suwannasin S, Hirankarn N, Tangkijvanich P, Boonla C (2017) Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression. Med Oncol 34:57

    Article  PubMed  Google Scholar 

  • Mohajeri M, Behnam B, Cicero A, Sahebkar A (2018) Protective effects of curcumin against aflatoxicosis: a comprehensive review. J Cell Physiol 233:3552–3577

    Article  CAS  PubMed  Google Scholar 

  • Nazhand A, Durazzo A, Lucarini M, Souto EB, Santini A (2020) Characteristics, occurrence, detection and detoxification of aflatoxins in foods and feeds. Foods 9

  • Oh SJ, Ikeda M, Ide T, Hur KY, Lee MS (2022) Mitochondrial event as an ultimate step in ferroptosis. Cell Death Discov 8:414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiao B, He Y, Gao X, Liu H, Rao G, Su Q, Ruan Z, Tang Z, Hu L (2023) Curcumin attenuates AFB1-induced duck liver injury by inhibiting oxidative stress and lysosomal damage. Food Chem Toxicol 172:113593

    Article  CAS  PubMed  Google Scholar 

  • Rainey NE, Moustapha A, Saric A, Nicolas G, Sureau F, Petit PX (2019) Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation. Cell Death Discov 5:150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruan D, Zhu YW, Fouad AM, Yan SJ, Chen W, Zhang YN, Xia WG, Wang S, Jiang SQ, Yang L, Zheng CT (2019) Dietary curcumin enhances intestinal antioxidant capacity in ducklings via altering gene expression of antioxidant and key detoxification enzymes. Poult Sci 98:3705–3714

    Article  CAS  PubMed  Google Scholar 

  • Rushing BR, Selim MI (2019) Aflatoxin B1: a review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem Toxicol 124:81–100

    Article  CAS  PubMed  Google Scholar 

  • Santana-Codina N, Gikandi A, Mancias JD (2021) The role of NCOA4-mediated ferritinophagy in ferroptosis. Adv Exp Med Biol 1301:41–57

    Article  CAS  PubMed  Google Scholar 

  • Wan F, Tang L, Rao G, Zhong G, Jiang X, Wu S, Huang R, Tang Z, Ruan Z, Chen Z, Hu L (2022) Curcumin activates the Nrf2 pathway to alleviate AFB1-induced immunosuppression in the spleen of ducklings. Toxicon 209:18–27

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Wang Y, Feng T, Yan Z, Zhu D, Lin H, Iqbal M, Deng D, Kulyar MF, Shen Y (2023) Hedyotis diffusa alleviate aflatoxin B1-induced liver injury in ducks by mediating Nrf2 signaling pathway. Ecotoxicol Environ Saf 249:114339

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Wang T, Nepovimova E, Long M, Wu W, Kuca K (2022a) Progress on the detoxification of aflatoxin B1 using natural anti-oxidants. Food Chem Toxicol 169:113417

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Liu F, Zhou X, Liu M, Zang H, Liu X, Shan A, Feng X (2022b) Alleviation of oral exposure to aflatoxin B1-induced renal dysfunction, oxidative stress, and cell apoptosis in mice kidney by curcumin. Antioxidants 11

  • Wang Y, Song M, Wang Q, Guo C, Zhang J, Zhang X, Cui Y, Cao Z, Li Y (2022c) PINK1/Parkin-mediated mitophagy is activated to protect against AFB(1)-induced kidney damage in mice. Chem Biol Interact 358:109884

    Article  CAS  PubMed  Google Scholar 

  • Xie J, Lv H, Liu X, Xia Z, Li J, Hong E, Ding B, Zhang W, Chen Y (2023) Nox4-and Tf/TfR-mediated peroxidation and iron overload exacerbate neuronal ferroptosis after intracerebral hemorrhage: involvement of EAAT3 dysfunction. Free Radical Biol Med 199:67–80

    Article  CAS  Google Scholar 

  • Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu K, Zhang J, Cao Z, Ji Q, Han Y, Song M, Shao B, Li Y (2018) Lycopene attenuates AFB1-induced renal injury with the activation of the Nrf2 antioxidant signaling pathway in mice. Food Funct 9:6427–6434

    Article  CAS  PubMed  Google Scholar 

  • Yuan Y, Yucai L, Lu L, Hui L, Yong P, Haiyang Y (2022) Acrylamide induces ferroptosis in HSC-T6 cells by causing antioxidant imbalance of the XCT-GSH-GPX4 signaling and mitochondrial dysfunction. Toxicol Lett 368:24–32

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Wang T, Li P, Chen J, Nepovimova E, Long M, Wu W, Kuca K (2021) Bacillus amyloliquefaciens B10 can alleviate aflatoxin B1-induced kidney oxidative stress and apoptosis in mice. Ecotoxicol Environ Saf 218:112286

    Article  CAS  PubMed  Google Scholar 

  • Zhu YT, Wan C, Lin JH, Hammes HP, Zhang C (2022) Mitochondrial oxidative stress and cell death in podocytopathies. Biomolecules 12

  • Zhuang Y, Yang D, Shi S, Wang L, Yu M, Meng X, Fan Y, Zhou R, Wang F (2022) MiR-375-3p Promotes cardiac fibrosis by regulating the ferroptosis mediated by GPX4. Comput Intell Neurosci 2022:9629158

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (31402264); the Project of Traditional Chinese Medicine Bureau of Guangdong Province (20221285); the Educational Commission of Guangdong Province, China (2021KTSCX012); the Nanning City Science Research and Technology Development Program (2022043); the Independent research project of Guangxi Key Laboratory of Veterinary Biotechnology (20-065-23-A-2); the Innovation Project of Universities in Guangdong Province (2021ZDZX2072); and the Guangxi Science and Technology Bureau (AA18118051).

Author information

Authors and Affiliations

Authors

Contributions

Haiyan Liu: conceptualization, data curation, validation, and writing—original draft. Ying He and Zhiyan Ruan: funding acquisition. Xinglin Gao, Baoxin Qiao, and Qian Su: software and validation. Tong Li: investigation. Lixuan Tang, Juan Lan: data curation and resources. Zhaoxin Tang: resources. Lianmei Hu: conceptualization, validation, writing (review and editing), and project administration.

Corresponding author

Correspondence to Lianmei Hu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 9801 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, H., He, Y., Gao, X. et al. Curcumin alleviates AFB1-induced nephrotoxicity in ducks: regulating mitochondrial oxidative stress, ferritinophagy, and ferroptosis. Mycotoxin Res 39, 437–451 (2023). https://doi.org/10.1007/s12550-023-00504-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12550-023-00504-3

Keywords

Navigation