Nephro- and hepatotoxicity of uranyl acetate in 18-week chronic administration to rats

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Abstract

The paper presents the results of an experimental study of the hepato- and nephrotoxicity of uranyl acetate dihydrate (UA) in 18-week chronic intragastric administration in doses of 0,5 and 5,0 mg/kg of the element. The study was performed on 45 male mongrel rats. A dose-dependent change in laboratory biochemical parameters of blood and urine of rats treated with the toxicant was revealed. Nephrotoxicity is characterized by multiple disorders of the functions of the proximal and distal tubules and glomeruli of nephrons. A pathoanatomic study revealed gross violations in the liver and kidney cytoarchitectonics of rats treated with UA in a dose of 5,0 mg/ kg. In liver, there were uneven regenerative phenomena in the form of nucleomegaly, the development of granular protein dystrophy of various degrees (up to necrosis), periportal lymphohistiocytic infiltration and periportal fibrosis. In kidneys, there were the development of chronic diffuse tubulointerstitial nephrofibrosis with significant lymphoplasmocytic infiltration, atrophy of the epithelium of the proximal and distal tubules, cystic transformation of the renal parenchyma.

About the authors

K. V. Sivak

Smorodintsev Research Institute of Influenza

Author for correspondence.
Email: kvsivak@gmail.com

Sivak Konstantin Vladimirovich

197376, Saint Petersburg

Russian Federation

K. I. Stosman

Smorodintsev Research Institute of Influenza; Institute of Toxicology of the Federal Medical and Biological Agency

Email: labtox6@rambler.ru

Stosman Kira Iosifovna

197376, Saint Petersburg
192019, Saint Petersburg

Russian Federation

T. N. Savateeva-Lubimova

Smorodintsev Research Institute of Influenza

Email: drugs_safety@mail.ru

Savateeva-Lubimova Tatyana Nikolaevna

197376, Saint Petersburg

Russian Federation

References

  1. Sivak K.V., Stosman K.I., SavateevaLjubimova T.N. Functional state of kidneys and immunological violations in acute combined effects of depleted uranium. Mediko-biologicheskie i social’nopsihologicheskie problemy bezopasnosti v chrezvychajnyh situaciyah. 2017; 2: 93–8 (in Russian).
  2. Poisson C., Stefani J., Mannens L., Delissen J., Suhard D., Tessier C., Dublineau I., Gueguen Y. Chronic uranium exposure dose-dependently induces glutathione in rat without any nephrotoxicity. Free Radical research. 2014; 48 (10): 1218–31 (in English).
  3. Zhu G., Xiang X., Chen X., Wang L., Hu H., Weng S. Renal dysfunction induced by long-term exposure to depleted uranium in rats. Arch Toxicol. 2009; 83: 37– 46 (in English).
  4. Selden A. I., Lundholm C., Edlund B., Hogdahl C., Ek B. M., Bergstrom B. E., Ohlson C. G. Nephrotoxicity of uranium in drinking water from private drilled wells. Environ. Res. 2009; 109: 486–94 (in English).
  5. Zamora M. L., Zielinski J. M., Moodie G. B., Falcomer R. A., Hunt W. C., Ca-pello K. Uranium in drinking water: renal effects of longterm ingestion by an aboriginal community. Arch. Environ. Occup. Health. 2009; 64: 228–41 (in English).
  6. Taulan M., Paquet F., Maubert C., Delissen O., Demaille J., Romey M.-C. Renal toxicogenomic response to chronic uranyl nitrate insult in mice. Environ. Health Perspectives. 2004; 112 (16): 1628–35 (in English).
  7. Yuhui Hao, Jiong Ren, Jing Liu, Shenglin Luo, Ting Ma, Rong Lim, Yongping Su. The protective role of zinc against acute toxicity of depleted uranium in rats. Basic & Clinical Pharmacology & Toxicology. 2012; 111: 402–10 (in English).
  8. Gueguen Y., Rouas C., Monin A., Manens L., Stefani J., Delissen O. et al. Molecular, cellular, and tissue impact of depleted uranium on xenobioticmetabolizing enzymes. Archi Toxicol. 2014;88: 227–39 (in English).
  9. Taha J. A Taha, Abdul Razak N .Khudayar, Zeinab A. J.R Al-Ali. Some hematological and bio chemical evaluation of sheep reared in areas exposed to depleted uranium. Bas. J. Vet. Res. 2009; 8 (1). – electronic publication.
  10. Dublineau I., Souidi M., Gueguen Y. et. al. Unexpected lack of deleterious effects of uranium on physiological systems following a chronic oral intake in adult rat. Biomed Res Int. 2014; 2014: 24 (in English).
  11. Gueguen Y., Rouas C., Monin A. et. al. Molecular, cellular, and tissue impact of depleted uranium on xenobioticmetabolizing enzymes. Arch Toxicol. 2014; 88: 227–39 (in English).
  12. Kalistratova V.S., red. Radiobiology of incorporated radionuclides. М.: Izdatel’stvo FMBC im. A.I. Burnazyana FMBA Rossii; 2012 (in Russian).
  13. Directive 2010/63/EU of the European Parliament and of the Council of the European Union for the protection of animals used for scientific purposes. SPb., 2012. (in Russian).
  14. Nandini C.D., Sambaiah K., Salimath P.V. Dietary fibers ameliorate decreased synthesis of heparin sulfate in streptozotocin induced diabetic rats. The Journal of Nutritional Biochemistry. 2003; 14: 203-10 (in English).
  15. Mazaheri M., Samaie A., Semnani V. Renal tubular dysfunction measured by N-acetyl-beta-glucosaminidase/ Creatinine activity index in children receiving antiepileptic drugs: a randomized controlled trial. Italian Journal of Pediatrics. 2011; 37(21): 4 (in English).
  16. Witko–Sarsat V., Friedlander M., Khoa T.N. et al. Advanced Oxidation Protein Products as Novel Mediators of Inflammation and Monocyte activation in chronic Renal Failure. The Journal of Immunology. 1998; 161: 2524–32 (in English).
  17. Karpishchenko A.I., red. Medical laboratory technology. T.2. SPb: Intermedika, 2002 (in Russian).
  18. Imamura K., Maruyama T., Okabe H., Shimada H., Otagiri M. A simple and rapid fluorimetric determination method of a-1-acid glycoprotein in serum using quinaldine red. Pharmaceutical Research. 1994;11(4):566-70 (in English).
  19. Sivak K.V. Mechanisms of nephropathology of toxic genesis. Patogenez. 2019; 17(2): 16-29 (in Russian).
  20. Demidchik L.A., Bejnikova I.V., Muravlyova L.E., Molotov-Luchanskij V.B., Bakirova R.E., Klyuev D.A., Utibaeva R.A. Oxidized proteins in the blood of patients with acute acetic acid poisoning. Mezhdunarodnyj zhurnal prikladnyh i fundamental’nyh issledovanij. 2018; 5-1: 82–6 (in Russian).
  21. Cao W., Hou F.F., Nie J. AOPPs and the progression of kidney disease. Kidney Int Suppl. 2014; 4(1): 102–6 (in English).
  22. Zhou L.L., Hou F.F., Wang G.B., Yang F., Xie D.,Wang Y.P., Tian J.W. A ccumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NAD PH-dependent mechanisms. Kidney Int. 2009; 76:1148–60 (in English).
  23. Cao W., Xu J., Zhou Z.M., Wang G.B., Hou F.F., Nie J. Advanced oxidation protein products activate intrarenal reninangiotensin system via a CD 36-mediated, redox-dependent pathway. Antioxid Redox Signal. 2013; 18: 19–35 (in English).

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