Effects of favipiravir on hematologic parameters and bone marrow in the rats

Year 2022, Volume: 39 Issue: 1, 156 - 159, 01.01.2022

Tuğçe Atçalı Seda Yakut Cüneyt Çağlayan Aykut Ulucan Adem Kara

Abstract

Favipiravir, a selective RNA polymerase inhibitor agent, is an antiviral drug currently used effectively in treating pandemic diseases such as Covid-19. The present study aims to determine the effects of favipiravir use on bone marrow and blood cells. Twelve male Wistar rats were divided into two groups, namely control and favipiravir groups. Physiological saline at a dose of 1 ml/kg was administered to the rats in the control group by oral gavage for 10 days. Rats in the favipiravir group were administered favipiravir by oral gavage at a dose of 200 mg/kg for 10 days. At the end of the study, the blood tissue was collected from the heart, and bone marrow samples were collected from the femur bone of the rats sacrificed under anesthesia. The hematologic parameters in the blood samples obtained were measured using an auto-analyzer device with the help of rat compatible kits. Bone marrow cell counts were performed by examining structural changes and myeloid and erythroid cell series in the smear samples. The results obtained in the study revealed that favipiravir use caused a decrease in the counts of some hematologic parameters containing erythrocytes, lymphocytes, and monocytes. In addition, it was determined that the ratio of myeloid and erythroid cells in bone marrow smears changed significantly with the use of favipiravir. It was concluded that treatment with favipiravir caused suppression of erythrocyte and some leukocyte series. The suppressor effects were also determined in bone marrow cell series in the rats.

Keywords

Bone marrow, Favipiravir, rats, RBC, WBC.

References

• Arai K, Kuramitsu K, Fukumoto T, Kido M, Takebe A, Tanaka M, et al. A case report of drug-induced thrombocytopenia after living donor liver transplantation. Kobe J Med Sci. 2016; 62(1): E9.
• Bolliger AP. Cytologic evaluation of bone marrow in rats: indications, methods, and normal morphology. Vet Clin Pathol. 2004; 33(2): 58-67.
• Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013; 100(2): 446-54.
• Goldhill DH, Te Velthuis AJ, Fletcher RA, Langat P, Zambon M, Lackenby A, et al. The mechanism of resistance to favipiravir in influenza. PNAS. 2018; 115(45): 11613-11618.
• Gowen BB, Juelich TL, Sefing EJ, Brasel T, Smith JK, Zhang L, et al. Favipiravir (T-705) inhibits Junin virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever, Plos Neglect Trop D.2013; 7(12): e2614.
• John MAA, Rhemtula YA, Menezes CN, Grobusch MP. Lamivudine-induced red cell aplasia. J Med Microbiol. 2008; 57(8): 1032-1035.
• McHutchison JG, Manns MP, Brown RS, Reddy KR, Shiffman ML, et al. Strategies for managing anemia in hepatitis C patients undergoing antiviral therapy. Am J Gastroenterol. 2007; 102(4): 880-889.
• Mendenhall M, Russell A, Juelich T, Messina EL, Smee DF, Freiberg AN, et al. T-705 (favipiravir) inhibition of arenavirus replication in cell culture. J Antimicrobial agents Nunberg, and chemotherapy. 2011; 55(2): 782-787.
• Millar JL, Blackett NM. The effect of various cytotoxic agents on the erythroid precursors in rat bone marrow. Br J Haematol. 1974; 26(4): 535-541.
• Mintzer DM, Billet SN, Chmielewski L. Drug-induced hematologic syndromes. Adv Hematol. 2009.
• Musa S. Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now? Arab J Gastroenterol. 2020; 21(1): 3-8.
• Schomaker SJ, Clemo FA, Amacher DE. Analysis of rat bone marrow by flow cytometry following in vivo exposure to cyclohexanone oxime or daunomycin HCl. Toxicol Appl Pharmacol. 2002; 185: 48-54.
• Tanaka N, Ishida F, Tanaka E. Ribavirin-induced pure red-cell aplasia during treatment of chronic hepatitis C. NEJM. 2004; 350(12): 1264-1265.
• Ulich TR, Del Castillo J. The hematopoietic and mature blood cells of the rat: their morphology and the kinetics of circulating leukocytes in control rats. Experimental hematology. 1991; 19(7), 639-648.
• Yaylaci S, Dheir H, Şenocak D, Genc AB, Kocayigit H, Çekiç D, et al. The effects of favipiravir on hematological parameters of covıd-19 patients. RAMB. 2020; 66: 65-70.
• Zhu W, Zhang Z, He S, Wong G, Banadyga L, Qiu X. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral research, 2018; 151: 39-49.