Histopathological effects of quercetin on liver tissue damage induced by iron oxide and iron oxide nanoparticles in Wistar rats

authors:

avatar Masoumeh Dadpey , avatar kiavash farahi , * , avatar Khodayar Ghorban , avatar Maryam Dadmanesh


how to cite: Dadpey M, farahi K, Ghorban K, Dadmanesh M. Histopathological effects of quercetin on liver tissue damage induced by iron oxide and iron oxide nanoparticles in Wistar rats. koomesh. 2019;21(3):e153112. 

Abstract

Introduction: Industrial and environmental pollution, excessive iron supplementation and blood transfusion are among the factors that may cause iron toxicity. Therefore, it is necessary to identify the mechanisms influencing or protecting against iron toxicity. The present study aimed to investigate the protective effects of quercetin as an antioxidant on hepatotoxicity induced by iron oxide and nano-iron oxide. Materials and Methods: The study was conducted on 30 Wistar rats (five groups): A) control group, B) nano-iron oxide, C) iron oxide, D) nano-iron oxide plus quercetin, and E) iron oxide plus quercetin. Nano-iron oxide and iron oxide were administered in daily doses of 20mg/kg, and quercetin in daily doses of 100mg/kg by intraperitoneal injection for 15 days. Correspondingly, the rats were then euthanized and their liver tissue was transferred to the pathology lab in 10% formalin. Samples were examined by conventional histopathological techniques using the Hematoxylin & Eosin, and Perls’ Prussian blue staining methods, and observed under the optical microscope. Results: The findings showed that nano-iron oxide and iron oxide can lead to inflammation in hepatic lobules and portal triads, sinusoidal dilatation, abnormal proliferation of the hepatocytes and Kupffer cells, and some hepatocyte degeneration. Simultaneous quercetin treatment was found to reduce the histopathological effects of metal particles, particularly iron oxide particles. Moreover, samples were tested for signs of bile retention, fibrosis and necrosis, but the results were negative. Conclusion: The present study confirmed the anti-inflammatory and protective effects of quercetin as an herbal antioxidant on hepatotoxicity induced by nano-iron oxide and iron oxide.  

References

  • 1.

    Kolesarova A, Capcarova M, Medvedova M, Sirotkin A, Kovacik J. In vitro assessment of iron effect on porcine ovarian granulosa cells: secretory activity, markers of proliferation and apoptosis. Physiol Res 2011; 60: 503-510.

  • 2.

    Szalay B, Ttrai E, Nyr G, Vezr T, Dura G. Potential toxic effects of iron oxide nanoparticles in in vivo and in vitro experiments. J Appl Toxicol 2012; 32: 446-453.

  • 3.

    Au KW, Liao SY, Lee YK, Lai WH, Ng KM, Chan YC, et al. Effects of iron oxide nanoparticles on cardiac differentiation of embryonic stem cells. Biochem Biophys Res Commun 2009; 379: 898-903.

  • 4.

    Park EJ, Kim H, Kim Y, Yi J, Choi K, Park K. Inflammatory responses may be induced bya single intratracheal instillation of iron nanoparticles in mice. Toxicology 2010; 275: 65-71.

  • 5.

    Prijic S, Scancar J, Cemazar M, Bregar VB, Znidarsic A, Sersa G. Increased cellular uptake of biocompatible superparamagnetic iron oxide nanoparticles into malignant cells by an external magnetic field. J Membr Biol 2010; 236: 167-179.

  • 6.

    Najafzadehvarzi H. Nano-Pharmacology. Ahwaz: Kerdegar; 2011. (Persian).

  • 7.

    Lekawanvijit S, Chattipakorn N. Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 2009; 25: 213-218.

  • 8.

    Krej J, Pachernk J, Hampl A, Dvok P. In vitro labelling of mouse embryonic stem cells with SPIO nanoparticles. Gen Physiol Biophys 2008; 27: 164-173.

  • 9.

    Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharmacol 2005; 202: 199-211.

  • 10.

    Jalali MR, Morovvati H, Najafzade H, Jalali S. Protective effects of silymarin and deferoxamine on iron over-load induced nephrotoxicity in rats. Biochem Cell Arch 2009; 9: 201-206.

  • 11.

    Jaymand K, Rezaie Mb, Osareh Mh, oghadaie SrT, Meshkizadeh S. Evaluation of flavonoids Rosa damascena Mill species. J Med Plants 2010; 9: 161-168.

  • 12.

    Shahidi F, Naczk M. Contribution of phenolic compounds to flavor and color characteristics of foods. Phenol Food Nutr 2004; 443-463. (Persian).

  • 13.

    Zaveri NT. Green tea and its polyphenolic catechins: medicinal uses incancer and noncancer applications. Life Sci 2006; 78: 2073-2080.

  • 14.

    Derakhshanian H, Marjanmehr SH, Ghadbeigi S, Rahimi N, Mostafavi SA, Hosseinzadeh P, Salehpour A, Dehpour AR. Evaluation of the protective effects of quercetin in biliary cirrhoticrats. Tehran Univ Med Sci 2013; 71. (Persian).

  • 15.

    Mohajeri D, Monadi A, Kaffashi ER, Neshat GM. Study on the protective effects of quercetin on methotrexate-induced small intestinal damage in the rat. 2015. (Persian).

  • 16.

    Wattel A, Kamel S, Prouillet C, Petit JP, Lorget F, Offord E, Brazier M. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NFB and AP1. J Cell Biochem 2004; 92: 285-295.

  • 17.

    Kim H, Kong H, Choi B, Yang Y, Kim Y, Lim MJ, Neckers L, Jung Y. Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease. Pharm Res 2005; 22: 1499-1509.

  • 18.

    Szalay B. Iron oxide nanoparticles and their toxicological effects: in vivo and in vitro studies: szte; 2012.

  • 19.

    Bahadori M. Histology technique and dyeing methods. Tehran Univ Press 1990. (Persian).

  • 20.

    Noori A, Amiri GR, Taj B, Isfahani MN, Taj S, Valiani A. The effect of magnetic iron oxide nanoparticles on mice liver and kidney. J Kerman Univ Med Sci 2012; 19: 243-252. (Persian).

  • 21.

    Chaves S, Lacava L, Lacava Z, Silva O, Pelegrini F, Buske N, et al. Light microscopy and magnetic resonance characterization of a DMSA-coated magnetic fluid in mice. IEEE Transactions Magnetics 2002; 38: 3231-3233.

  • 22.

    Aydin B. Quercetin prevents methotrexate-induced hepatotoxicity without interfering with methotrexate metabolizing enzymes in liver of mice. J Appl Biol Sci 2011; 5: 75-80.

  • 23.

    Murphy EA, Davis JM, McClellan JL, Steiner JL, Waghmare S, Jung SH, Carmichael MD. Effects of curcumin and quercetin on intestinal inflammation in the Apc/Min+ Mouse: 685: Board# 4 3: 15 PM-5: 15 PM. Med Sci Sports Exerc 2011; 43: 48-49.

  • 24.

    Kim YJ, Bae YC, Suh KT, Jung JS. Quercetin, a flavonoid, inhibits proliferation and increases osteogenic differentiation in human adipose stromal cells. Biochem Pharmacol 2006; 72: 1268-1278.

  • 25.

    Chen X. Protective effects of quercetin on liver injury induced by ethanol. Pharmacogn Mag 2010; 6: 135-141.

  • 26.

    Wisse E, Doucet D, Van Bossuyt H. A transmission electron microscopic study on the uptake of AMI-25 by sinusoidal liver cells. Cell Hepatic Sinusoid 1991; 3: 534-539.

  • 27.

    Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 2010; 48: 3246-3261.

  • 28.

    Edremitliolu M, Andi MF, Korkut O. Quercetin, a powerful antioxidant bioflavonoid, prevents oxidative damage in different tissues of long-term diabetic rats. Balkan Med J 2012; 2012.

  • 29.

    Kmie Z. Cooperation of Liver Cells in the Synthesis and Degradation of Eicosanoids. Cooperation of Liver Cells in Health and Disease: Springer; 2001; p: 51-59.

  • 30.

    Naqvi S, Samim M, Abdin M, Ahmed FJ, Maitra A, Prashant C, Dinda AK. Concentration-dependenttoxicity of iron oxide nanoparticles mediated by increased oxidative stress. Int J Nanomedicine 2009; 5: 983-989.

  • 31.

    Babadi VY, Najafi L, Najafi A, Gholami H, Zarji ME, Golzadeh J, et al. Evaluation of iron oxide nanoparticles effects on tissue and enzymes of liver in rats. J Pharm Biomed Sci 2012; 23: 1-4. (Persian).

  • 32.

    Batta A. Comparative study of serum 5'nucleotidase, alkaline phosphatase, aminotransferases and bilirubin in hepatpbilrary diseases. Int J Cur Biomed Phar Res 2011; 1: 93-97.

  • 33.

    Kawada N, Seki S, Inoue M, Kuroki T. Effect of antioxidants, resveratrol, quercetin, and Nacetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology 1998; 27: 1265-1274.

  • 34.

    Xiong D, Fang T, Yu L, Sima X, Zhu W. Effects of nano-scale TiO 2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. Sci Total Environ 2011; 409: 1444-1452.

  • 35.

    Samal N, Paulraj R, editors. Combined roleof magnetic iron oxide nanoparticles and 2.45 GHz microwave radiation on antioxidant enzymes of mice. Electromagnetics in Advanced Applications (ICEAA), 2010 International Conference on; 2010: IEEE.

  • 36.

    Shirband A, Azizian H, Pourentezari M, Rezvani ME, Anvari M, Esmaeilidehaj M. Dose-dependent effects of iron oxide nanoparticles on thyroid hormone concentrations in liver enzymes: Possible tissue destruction. Global J Med Res Studi 2014; 1: 28-31. (Persian).

  • 37.

    Morales A, Vicente-Sanchez C, Sandoval JS, Egido J, Mayoral P, Arvalo M, et al. Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem Toxicol 2006; 44: 2092-2100.

  • 38.

    Dillard CJ, German JB. Phytochemicals: nutraceuticals and human health. J Sci Food Agricul 2000; 80: 1744-1756.