MACROPHAGE GRANULOMAS AND MAST CELLS AS BEGINNING ORGAN REMODELING IN CASE OF SILICONE DIOXIDE NANOPARTICLES CHRONIC TOXICITY

We studied 12-16 nm spherical silicone dioxide nanoparticles chronic toxicity on Wistar male rats (middle weight 250-300 g). We intravenously injected 1 ml silicone dioxide nanoparticles suspension and evaluated histological modifications in organs after 7, 21 and 60 days after injection. We detected mast cell migration into lungs, myocardium and liver tissues. Also we revealed macrophage granulomas around foreign bodies formation and liver tissue fibrous remodeling. This remodeling took place without precedence of destruction. We noticed that silicone dioxide nanoparticles injection was accompanied by evolution of chronic aseptic productive inflammation. The same type of inflammation take place in case of non-modified nanoparticles silicone dioxide intervention in sylicosis.

диоксид кремния, наночастицы 12-16 нм, хроническая in vivo токсичность, миграция тучных клеток, макрофагальные гранулемы, «гранулемы инородных тел», печеночный фиброз, соединительнотканное ремоделирование ткани, silicone dioxide, silicone nanoparticles 12-16 nm, silicone fibrosis, chronic in vivo toxicity, mast cells migration, macrophage granulomas, granuloma around foreign body, connective tissue remodeling, hepatic fibrosis, foreign body reaction

1. Naumysheva EB, Umenushkina EV, Evreinova NV et al. Biodegradation and biocompatibility of nanosized silica as a carrier for targeted drug delivery. Nanotehnologii i ohrana zdorov’ja=Nanotechnology and public health. 2011; 2: 30-36. In Russian. [Наумышева Е.Б, Уменушкина Е.В, Евреинова Н.В. и др. Биодеградация и биосовместимость нанодисперсного кремнезема как носителя для направленной доставки лекарственных препаратов. Нанотехнологии и охрана здоровья. 2011; 2: 30-36].

2. Galagudza M, Korolev D, Sonin D, et al. Targeted drug delivery to ischemic heart with use of nanoparticulate carriers: Concepts, pitfalls and perspectives. Journal of Manufacturing Technology Management. 2010; 21(8): 930-949.

3. Slowing II, Vivero-Escoto JL, Wu CW, et al. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug Deliv. Rev. 2008; 60(11): 1278-1288.

4. Malvindi MA, Brunetti V, Vecchio G, et al. SiO2 nanoparticles biocompatibility and their potential for gene delivery and silencing. Nanoscale. 2012; 4: 486-495.

5. Uboldi C, Giudetti G, Broggi F, et al. Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. Mutat Res. 2012; 745:11-20.

6. Andreeva ER, Rudimov EG, Gornostaeva AN, et al. In vitro study of interactions between silicon-containing nanoparticles and human peripheral blood leukocytes. Bull Exp Biol Med. 2013; 155(3): 396-398.

7. Galagudza M, Korolev D, Postnov V, et al. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles. International Journal of Nanomedicine. 2012; 7: 1671-1678.

8. Ivanov S, Zhuravsky S, Yukina G, et al. In vivo toxicity of intravenously administered silica and silicon nanoparticles. Materials. 2012; 5: 1873-1889.

9. Kumar R, Roy I, Ohulchanskky TY, et al. In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles. ACS Nano. 2010; 4(2): 699-708.

10. Yoon Yeo. Nanoparticulate drug delivery dystems: strategies, technologies and applications. 2013. 324 p. Xie G, Sun J, Zhong G, et al. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Archives of Toxicology. 2010; 84(3):183-190.

11. Shkurupy VA, Nadeev AP, Karpov MA, et al. Experimental cytomorphological studies of the reaction of mononuclear phagocyte system in granulomatosis of mixed (silicotic and tuberculous) etiology. Bull. Exp. Biol. Med. 2010; 149(4): 462-465.

12. Lemaire I. Silica- and asbestos-induced pulmonary fibrosis. In: Phan S.H, Thrall R.S, editors. Pulmonary Fibrosis. New York: Marcel Dekker, 1995. 319-362.

13. Deb U, Lomash V, Raghuvanshi S, et al. Effects of 28 days silicon dioxide aerosol exposure on respiratory parameters, blood biochemical variables and lung histopa-thology in rats. Environ. Toxicol. Pharmacol. 2012; 34(3): 977-984.

14. Lakatos HF, Burgess HA, Thatcher TH, et al. Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation. Exp. Lung Res. 2006; 32(5): 181-199.

15. Hamilton RF Jr, Thakur SA, Holian A. Silica binding and toxicity in alveolar macrophages. Free Radic. Biol. Med. 2008; 44(7): 1246-1258.

16. Suzuki N, Horiuchi T, Ohta K, et al. Mast cells are essential for the full development of silica-induced pulmo nary inflammation: a study with mastcell-deficient mice. Am. J. Respir. Cell Mol. Biol. 1993; 9(5): 475-483.

17. Kawanami O, Ferrans VJ, Fulmer JD, et al. Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders. Lab. Invest. 1979; 40(6): 717-734.

18. Hoppstädter J, Seif M, Dembek A, et al. M2 polarization enhances silica nanoparticle uptake by macrophages. Front Pharmacol. 2015; 6: 55.

19. Bykov VL, Pryanishnikov VA. Quantitative histochemical and stereological study of alkaline phosphatase in rat thyroid gland. Histochemistry. 1978; 58: 129-134.

20. Yu Y, Li Y, Wang W, et al. Acute toxicity of amorphous silica nanoparticles in intravenously exposed ICR mice. PLoS One. 2013;8(4).

21. Shkurupiy VA, Kim LB, Potapova OV, et al. Fibrogenesis in granulomas and lung interstitium in tuberculous inflammation in mice. Bull. Exp. Biol. Med. 2014; 15(66): 731-735.

22. Kumasaka T, Akaike Y, Nakamura O, et al. Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages. Pathol. Int. 2011; 61(11): 667-671.

23. Liu T, Li L, Fu C, et al. Pathological mechanisms of liver injury caused by continuous intraperitoneal injection of silica nanoparticles. Biomaterials. 2012; 33(7): 2399-2407.

24. Kojima S, Negishi Y, Tsukimoto M, et al. Purinergic signaling via P2X7 receptor mediates IL-1β production in Kupffer cells exposed to silica nanoparticle. Toxicology. 2014; 321: 13-20.

25. Puxeddu I, Piliponsky AM, Bachelet I, et al. Mast cell in allergy and beyond. Int. J. Biochem. Cell Biol. 2003; 35: 1601-1607.

26. Takato H, Yasui M, Ichikawa Y, et al. The specific chymase inhibitor TY-51469 suppresses the accumulation of neutrophils in the lung and reduces silica-induced pulmonary fibrosis in mice. Exp. Lung Res. 2011; 37(2): 101-108.

27. Kosanovic D, Dahal BK, Wygrecka M, et al. Mast cell chymase: an indispensable instrument in the pathological symphony of idiopathic pulmonary fibrosis? Histol. Histopathol. 2013; 28(6): 691-699.

28. Wallace WAH, Fitch PM, Simpson AJ, et al. Inflammation-associated remodelling and fibrosis in the lung - a process and an end point. Int. J. Exp. Pathol. 2007; 88(2): 103-110.

29. Herd HL, Bartlett KT, Gustafson JA, et al. Macrophage silica nanoparticle response is phenotypically dependent. Biomaterials. 2015; 53: 574-582.

30. Wake K. Karl Wilhelm Kupffer And His Contributions To Modern Hepatology. Comp Hepatol. 2004; 3: 1-6.

31. Burns AA, Vider J, Ow H, et al. Fluorescent silica nanoparticles with efficient urinary excretion for nanomedicine. Nano Lett. 2009; 9(1): 442-448.

32. Moore A, Marecos E, Bogdanov A, et al. Tumoral distribution of long-circulating dextran-coated iron oxide nano-particles in a rodent model. Radiology. 2000; 214: 568-574.

33. Delgado L, Parra ER, Capelozzi VL. Apoptosis and extracellular matrix remodelling in human silicosis. Histopathology. 2006; 49(3): 283-289.

34. Karpov MA, Skurupiy VA, Nadeev AP. Analysis of fibrotic depositions in granulomas in chronic silicotuberculosis in mice. Bull. Exp. Biol. Med. 2010; 149(5): 659-662.