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Ascorbigen — Rifabutin Toxicity Modifier

https://doi.org/10.37489/0235-2990-2020-65-9-10-13-20

Abstract

Relevance. Indications for rifabutin use are constantly expanding. It is used in the treatment of extremely complex nosological forms of infectious diseases. However, side effects of the medication, such as gastrointestinal toxicity and myelosuppression, in many cases do not allow the completion of treatment and weaken the patient-s adherence to therapy. This determines the need to find means to reduce the toxic properties of rifabutin.

Objective. The aim of the study was to investigate the possibility of correction of gastrointestinal and hematological toxicity of rifabutin with ascorbigen.

Material and Methods. The study was performed in male Wistar rats. The drugs were administered per os at therapeutic doses (50 mg/kg daily for 15 days). Ascorbigen was administered 30 minutes before rifabutin. Body weight dynamics, hematological parameters, blood biochemical parameters, electrocardiography, and urinalysis were performed for all animals during the study. Five animals in each group were euthanized on the 1st and 30th days after the end of the treatment course. The internal organs were subjected to histological evaluation.

Results. It has been shown that combined treatment with rifabutin and ascorbigen leads to a weakening of the damaging effect of the antibiotic on the mucous membrane of the gastrointestinal tract and accelerates the processes of restoration of its structure. Clinically, this is expressed in the normalization of body weight gain of animals. The combined use of rifabutin with ascorbigen reduces the depth of cytopenia. The number of leukocytes in the peripheral blood of the rats was restored faster. There were no signs of atrophy of spleen-s lymphoid tissue. The administration of ascorbigen before rifabutin has a protective effect on the tissues of the kidneys and testes.

Conclusion. Oral administration of ascorbigen 30 minutes before rifabutin significantly reduces the gastrointestinal toxicity and hematotoxicity of rifabutin and prevents the development of spermatogenesis disorders. This allows us to recommend it for combined use in order to improve tolerance to anti-TB treatment.

About the Authors

E. R. Pereverzeva
Gause Institute of New Antibiotics
Russian Federation
Moscow


M. I. Treshchalin
Gause Institute of New Antibiotics
Russian Federation
Moscow


I. D. Treshchalin
Gause Institute of New Antibiotics
Russian Federation
Moscow


References

1. Global tuberculosis report 2018. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1

2. Zdravookhranenie v Rossii. 2019: Stat.sb./Rosstat. M.: 2019; 170. [in Russian]

3. Global tuberculosis report 2019. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1

4. Tuberkulez organov dykhaniya u vzroslykh. Klinicheskie rekomendatsii. Ministerstvo zdravookhraneniya RF. MKB 10: A15/A16, 2018. [in Russian] http://obltub.ru/assets/files/2019/05.2019/klinicheskierekomendacii-tod-u-vzroslyh-2018.pdf

5. Crabol Y., Catherinot E., Veziris N., Jullien V., Lortholary O. Rifabutin: where do we stand in 2016? J Antimicrob Chemother 2016; 71: 1759–1771. doi:10.1093/jac/dkw024

6. Azis L., Jones-Lo´pez E.C., Ellner J.J. Chapter 26-HIV-associated tuberculosis, in Sande-s HIV/AIDS Medicine (Second Edition). 2012; 325–347. https://doi.org/10.1016/B978-1-4557-0695-2.00026-2

7. Datri 001 Study Group. Clarithromycin (CL) plus rifabutin (RFB) for VFC prophylaxis: evidence for a drug interaction. In: Abstracts of the 1st Nat Conf Human Retroviruses Related Infec. Washington 1993; Abstr 106

8. Treatment of tuberculosis: guidelines — 4th ed. WHO/HTM/TB/2009.420 https://apps.who.int/iris/bitstream/handle/10665/44165/9789244547830_rus.pdf?sequence=2

9. Tsybanev A.A., Sokolova G.B. Protivotuberkuleznyi antibiotik prolongirovannogo deistviya — rifabutin. Antimikrobnyi spektr, osobennosti farmakodinamiki i farmakokinetiki. Antibiotiki i khimioter 1999; 8: 30–36. [in Russian]

10. Wallace R.J., Philley J.V., Griffith D.E. Antimycobacterial Agents. Mandell, Douglas, and Bennett-s Principles and Practice of Infectious Diseases (Eighth Edition), V. 1, 2015; 463–478. e3 https://doi.org/10.1016/B978-1-4557-4801-3.00038-2

11. WHO consolidated guidelines on drug-resistant tuberculosis treatment. Geneva: World Health Organization; 2019. Consolidated-guidelines-drugresistant-TB-treatment/en/, accessed 17 July 2019. https://www.who.int/tb/publications2019

12. Dobbs T.E., Webb R.M. Chemotherapy of tuberculosis. Microbiol Spectr 2017; 5 (2): 1–16. doi:10.1128/microbiolspec.TNMI7-0040-2017

13. Kravchenko L.V., Avren-eva L.I., Guseva G.V., Posdnyakov A.L., Tutel-yan V.A. Effect of nutritional indoles on activity of xenobiotic metabolism enzymes and T-2 toxicity in rats. Bull Exp Biol Med 2001; 131 (6): 544–547. doi: 10.1023/a:1012346401315.

14. Mukhanov V.I., Yartseva I.V., Kikot- B.S., Volodin Yu.Yu., Kustova I.L., Lesnaya N.A. i dr. Izuchenie askorbigena i ego proizvodnykh. Bioorganicheskaya Khimiya 1984; 10: 4: 554–559. [in Russian]

15. Pereverzeva E.R., Treschalin I.D., Bodyagin D.A., Treschalin M.I., Preobrazhenskaya M.N., Bukhman V.M. Oral administration of ascorbigen accelerates the regeneration of small intestine and lymphoid organs of mice after injury caused by cyclophosphamide. Russian biotherapeutic journal 2005; 4 (4): 129–133. [in Russian]

16. European Convention for the protection of vertebrate animals used for experimental and other scientific purposes (Council of Europe, ETS No. 123). 1986.

17. Freireich E.J., Gehan E.A., Rall D.P., Schmidt L.H., Skipper H.E. Quantitative Comparison of Toxicity of Anticancer Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man. Cancer Chemother Rep 1966; 50 (4): 219–244. PMID: 4957125.

18. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Pod red. A.N. Mironova, M.: Grif i K. 2012; 1: 13–24. [in Russian]

19. Padmapriyadarsini C., Jawahar M.S. A worldwide yearly survey of new data in adverse drug reactions and interactions. Rifabutin. In: Side Effects of Drugs Annual 2014; 35: 551–563. https://doi.org/10.1016/B978-0-444-62635-6.00030-9

20. Verburg M., Renes I.B., Meijer H.P., Taminiau J.A., Büller H.A., Einerhand A.W. et. al. Selective Sparing of Goblet Cells and Paneth Cells in the Intestine of Methotrexate-Treated Rats. Am J Physiol Gastrointest Liver Physiol. 2000; 279 (5): G1037-47. doi: 10.1152/ajpgi.2000.279.5.G1037.

21. Verburg M., Renes I.B., Van Nispen D.J.P.M., Ferdinandusse S., Jorritsma M., Büller H.A. et. al. Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration. J Histochem Cytochem 2002; 50 (11): 1525–1536. doi: 10.1177/002215540205001113.

22. Seno H., Sawada M., Fukuzawa H., Morita-Fujisawa Y., Takaishi S., Hiai H. et al. Involvement of tumour necrosis factor alpha in the intestinal epithelial cell proliferation following Paneth cell destruction. Scand Gastroenterol 2002; 37 (2): 154–160. https://doi.org/10.1080/003655202753416803

23. Möller P., Walczak H., Reidl S., Sträter J., Krammer P.H. Paneth Cells Express High Levels of CD95 Ligand Transcripts: A Unique Property Among Gastrointestinal Epithelia. Am J Pathol 1996;49 (1): 9-13. PMID: 8686766

24. Ariza A., López D., Castellà E.M., Muñoz C., Zújar M.J., Mate J.L. Expression of CD15 in normal and metaplastic Paneth cells of the digestive tract. J Clin Pathol 1996; 49 (6): 474–477. doi:10.1136/jcp.49.6.474.

25. Hooper L.V., Stappenbeck T.S., Hong C.V., Gordon J.I. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003; 4 (3): 269–273. doi:10.1038/ni888

26. Brughera M., Scampini G., Newman A.J., Castellino S., Samantini U., Mazue G. Overview of toxicological data on rifabutin. Exp Toxic Patol 1995; 47: 1–9.


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For citations:


Pereverzeva E.R., Treshchalin M.I., Treshchalin I.D. Ascorbigen — Rifabutin Toxicity Modifier. Antibiot Khimioter = Antibiotics and Chemotherapy. 2020;65(9-10):13-20. (In Russ.) https://doi.org/10.37489/0235-2990-2020-65-9-10-13-20

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