Effect of antioxidants on lung self-cleaning from quartz dust in experimental silicosis in rats

Introduction. Silicosis remains one of the most common forms of pneumoconiosis among occupational lung diseases. However, effective preventive and therapeutic measures aimed at accelerating the removal of dust particles from the respiratory tract remain underdeveloped.

The aim of this study was to evaluate the feasibility of drugs with antioxidant properties available in pharmacies to stimulate lung self-clearance from quartz dust particles in a rat experimental model of silicosis.

Materials and methods. The study was performed in male Wistar rats that received a single intratracheal instillation of a standard quartz dust sample. Experimental groups were treated intraperitoneally with ethylmethylhydroxypyridine succinate (EMHPS) or dimethyloxybutylphosphonyldimethylate (DMOBPDM) for 4 weeks; 0.9% saline was used in the positive and negative control groups. At the end of the experiment, wet and dry lung weight, lung mass coefficient, dry weight index, wet to dry ratio, body weight gain, and the relative amount of quartz dust spontaneously removed from the lungs were determined.

Results. In the fibrotic groups, wet and dry lung weights were significantly higher than in controls, accompanied by a tendency toward reduced body weight gain. The relative amount of spontaneously removed quartz dust was significantly higher in the EMHPS group than in the positive control, whereas DMOBPDM did not increase dust clearance and yielded values did not exceed those in the control.

Conclusions. EMHPS enhances self clearance of quartz dust in experimental silicosis in rats, while DMOBPDM showed no such effect under the studied conditions. The results suggest the potential of systemic antioxidant drugs for the pathogenetic prevention and treatment of dust related lung diseases, including silicosis.

Contributions:
Tonshin A.A. — research concept and design, conducting experiments, collecting and processing experimental data, writing text;
Makarov A.F. — concept and design of research, conducting experiments, preparation of literature data;
Krikunov O.V. — conducting experiments;
Bidevkina M.V. — concept and design of research, conducting experiments, preparation of literature data;
Muravskaya M.P. — conducting experiments;
Nikolaev I.M. — conducting experiments;
Bonitenko E.Yu. — research concept and design, text writing, editing.

Funding. The study was carried out within the Framework of research project No. FGFE-2025-0023 of the state assignment.

Conflict of interest. The authors declare no conflict of interest.

Received: 21.05.2026 / Accepted: 25.05.2026 / Published: 27.06.2026

1. Hoy R.F., Chambers D.C. Silica-related diseases in the modern world. Allergy. 2020; 75(11): 2805–2817. https://doi.org/10.1111/all.14202

2. Salahuddin M., Cawasji, Z., Kaur S., Estrada-Y-Martin R.M., Cherian S.V. Current Concepts in Pathogenesis, Diagnosis, and Management of Silicosis and Its Subtypes. Curr. Pulmonol. Rep. 2021; 10: 135–142. https://doi.org/10.1007/s13665-021-00279-x

3. Hamilton R.F. Jr., Thakur S.A., Holian A. Silica binding and toxicity in alveolar macrophages. Free Radic. Biol. Med. 2008; 44(7): 1246–58. https://doi.org/10.1016/j.freeradbiomed.2007.12.027

4. Harijith A., Ebenezer D.L., Natarajan V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol. 2014; 5: 352. https://doi.org/10.3389/fphys.2014.00352

5. Kim B.Y., Han M.J., Chung A.S. Effects of reactive oxygen species on proliferation of Chinese hamster lung fibroblast (V79) cells. Free Radic. Biol. Med. 2001; 30(6): 686–98. https://doi.org/10.1016/s0891-5849(00)00514-1

6. Geng F., Xu J., Ren X., Zhao Y., Cai Y., Li Y. et al. Effect of macrophage-to-myofibroblast transition on silicosis. Animal Model Exp. Med. 2025; 8(2): 363–371. https://doi.org/10.1002/ame2.12470

7. Yang B., Liu X., Peng C., Meng X., Jia Q. Silicosis: from pathogenesis to therapeutics. Frontiers in pharmacology. 2025; 16: 1516200. https://doi.org/10.3389/fphar.2025.1516200

8. Joshi G.N., Knecht D.A. Silica phagocytosis causes apoptosis and necrosis by different temporal and molecular pathways in alveolar macrophages. Apoptosis. 2013; 18(3): 271–285. https://doi.org/10.1007/s10495-012-0798-y

9. Handra C.M., Gurzu I.L., Chirila M., Ghita I. Silicosis: new challenges from an old inflammatory and fibrotic disease. Front. Biosci. (Landmark Ed). 2023; 28(5): 96. https://clck.ru/3TqJHg

10. Iles K.E., Forman H.J. Macrophage signaling and respiratory burst. Immunol. Res. 2002; 26(1–3): 95–105. https://doi.org/10.1385/IR:26:1-3:095

11. Shen H.M., Zhang Z., Zhang Q.F., Ong C.N. Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 280(1): L10–L17. https://doi.org/10.1152/ajplung.2001.280.1.L10

12. Zhang B., Pan C., Feng C. et al. Role of mitochondrial reactive oxygen species in homeostasis regulation. Redox Rep. 2022; 27(1): 45–52. https://doi.org/10.1080/13510002.2022.2046423

13. Fubini B., Hubbard A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free radical Biology and medicine. 2003; 34(12): 1507–1516. https://doi.org/10.1016/s0891-5849(03)00149-7

14. Sun J., Song P., Wang Y., Chen Y. Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum IL-6 and TNF-α. Exp Ther Med. 2019; 18(5): 3383-3388. https://doi.org/10.3892/etm.2019.7966

15. Zhang J., Wang Y., Zhang S., Li J., Fang H. Effects of tetrandrine combined with acetylcysteine on exercise tolerance, pulmonary function and serum TNF-β1 and MMP-7 in silicosis patients. Experimental and Therapeutic Medicine. 2020; 19(3): 2195–2201. https://doi.org/10.3892/etm.2020.8431

16. Shi X., Mao Y., Saffiotti U., Wang L., Rojanasakul Y., Leonard S.S., et al. Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation. J. Toxicol. Environ Health. 1995; 46(2): 233–248. https://doi.org/10.1080/15287399509532031

17. Bhagya N., Chandrashekar K.R. Tetrandrine–A molecule of wide bioactivity. Phytochemistry. 2016; 125: 5–13. https://doi.org/10.1016/j.phytochem.2016.02.005

18. Raghu G., Berk M., Campochiaro P.A., Jaeschke H., Marenzi G., Richeldi L. et al. The multifaceted therapeutic role of N-acetylcysteine (NAC) in disorders characterized by oxidative stress. Current neuropharmacology. 2021; 19(8): 1202–1224. https://doi.org/10.2174/1570159X19666201230144109

19. Voronina T.A. Mexidol: the spectrum of pharmacological effects. S.S. Korsakov Journal of Neurology and Psychiatry. 2012; 112(12): 86–90. https://clck.ru/3TqEqC (in Russian).

20. Tsishba Е.А., Maksimov M.L. Dimethyloxobutylphosphonyl dimethylate (dimephosphone). Pharmacological effects. Neurotropic and cerebroprotective properties. Farmatsevticheskoe delo i tekhnologiya lekarstv. 2022; 4. https://doi.org/10.33920/med-13-2208-18 (in Russian).

21. Shekunova E.V., Kovaleva M.A., Makarova M.N., Makarov V.G. Dose Selection in Preclinical Studies: Cross-Species Dose Conversion. Vedomosti Nauchnogo tsentra ehkspertizy sredstv meditsinskogo primeneniya. 2020; 10(1): 19–28. https://doi.org/10.30895/1991-2919-2020-10-1-19-28 (in Russian).

22. Tonshin A.A., Makarov A.F., Krikunov O.V., Muravskaya M.P., Tkachuk Yu.V., Nikolaev I.M., Bonitenko E.U. Bronchoalveolar lavage as a method for removing aerosol particles with predominantly fibrogenic action. Russian Journal of Occupational Health and Industrial Ecology [Med. truda i prom. ekol.]. 2026; 66(3): 208–214. https://doi.org/10.31089/1026-9428-2026-66-3-208-214 (in Russian).

23. Bezrukavnikova L.M., Yaglov V.V., Kuz'mina L.P. Babok A.A. Fedosova N.F., Krasnyuk E.K. et al. Experimental study of the effectiveness of terrilitin in silicosis. Russian Journal of Occupational Health and Industrial Ecology [Med. truda i prom. ekol.]. 1993; 33(4): 20–22 (in Russian).

24. Maksimenko A.V., Bezrukavnikova L.M., Grigor'eva E.L., Tishchenko E.G., Arkhipova V.V., Yaglov V.V. et al. Antifibrotic effect of modified forms of catalase and superoxide dismutase in experimental silicosis. Voprosy meditsinskoy khimii. 1992; 38(3): 4–8. https://elibrary.ru/scxizx (in Russian).

25. Gusev V.A., Danilovskaya E.V. The effect of superoxide dismutase and catalase on the course of the pathological process in the lungs in experimental silicosis. Russian Journal of Occupational Health and Industrial Ecology [Med. truda i prom. ekol.]. 1998; 38(10): 17–21. https://elibrary.ru/mpaumz (in Russian).

26. Reiser K.M., Hesterberg T.W., Haschek W.M., Last J.A. Experimental silicosis. I. Acute effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs. Am. J. Pathol. 1982; 107(2): 176–185. https://clck.ru/3TqJEg

27. Fu N.F., Luo C.H., Wu J.C., Zheng Y.Y., Gan Y.J., Ling J.A., et al. Clearance of free silica in rat lungs by spraying with chinese herbal kombucha. Evidence‐Based Complementary and Alternative Medicine. 2013; 2013(1): 790792. https://doi.org/10.1155/2013/790792

28. Voronina T.A. Antioxidant mexidol. The main neuropsychotropic effects and mechanism of action. Psikhofarmakologiya i biologicheskaya narkologiya. 2001; 1(1): 2–12. https://clck.ru/3TqEuU (in Russian).

29. Belova Yu.A., Kotov S.V. Antioxidant therapy in the complex treatment of patients with ischemic stroke in the acute and recovery period. Nevrologiya, neyropsikhiatriya, psikhosomatika. 2023; 15(2): 120–125. https://clck.ru/3TqEvP (in Russian).

30. Valko M., Leibfritz D., Moncol J. et al. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell. Biol. 2007; 39(1): 44–84. https://doi.org/10.1016/j.biocel.2006.07.001

31. Arkhipova O.G., Ivanova A.S., Velichkovskiy B.T., Kupina L.M. Pavlovskaya L.V. et al. Basic principles of the search and experimental testing of pathogenetic prophylaxis and therapy of pneumoconiosis. Metodicheskie rekomendatsii. Moscow; 1979 (in Russian).