Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.
Toxicidad pulmonar asociada a altas dosis de favipiravir y opciones de tratamiento: Evaluación bioquímica e histopatológica.
Palabras clave:
Favipiravir, lacidipino, pirofosfato de tiamina, trifosfato de adenosina, estrés oxidativo
Resumen
El Favipiravir es un fármaco antiviral de amplio espectro que es un
inhibidor de la ARN polimerasa viral dependiente de ARN. El Favipiravir se usa en do-
sis altas para tratar el COVID-19, pero tiene efectos secundarios en humanos a estas
dosis. Los efectos secundarios del favipiravir se han asociado con el estrés oxidativo
en la literatura. En este trabajo experimental, investigamos los efectos bioquímicos
e histopatológicos de lacidipina, pirofosfato de tiamina (TTP) y trifosfato de adeno-
sina (ATP), fármacos con propiedades antioxidantes, sobre la toxicidad pulmonar
causada por altas dosis de favipiravir en ratas. Las ratas se clasificaron en cinco gru-
pos: sanas (HG), favipiravir solo (Fav), lacidipina+favipiravir (LFav), TPP+favipiravir
(TFav) y ATP+favipiravir (AFav). Se administró favipiravir (800 mg/kg) dos veces al
día durante siete días. Se administraron lacidipina (4 mg/kg), TPP (20 mg/kg) y
ATP (25 mg/kg) una vez al día durante siete días. Se midieron los niveles de antioxi-
dantes oxidantes (malondialdehído), no enzimáticos (glutatión total) y enzimáticos
(superóxido dismutasa y catalasa) en los tejidos pulmonares disecados. Además, los
tejidos fueron examinados histopatológicamente. La administración sistémica de
altas dosis de favipiravir aumentó los niveles de oxidantes y disminuyó los niveles
de antioxidantes en el tejido pulmonar de ratas. Paralelamente, el examen histopa-
tológico del tejido pulmonar reveló la presencia de graves infiltraciones de células
mononucleares en las zonas intersticiales y una pronunciada hiperplasia linfoide.
Lacidipina mostró una eficacia superior para mitigar el estrés oxidativo y prevenir
la disminución de antioxidantes inducida por favipiravir en comparación con TPP y
ATP. Histopatológicamente, la administración de lacidipina redujo significativamen-
te el daño oxidativo pulmonar. La TTP redujo moderadamente la lesión pulmonar
grave asociada al favipiravir. Sin embargo, el ATP fue ineficaz contra la lesión pul-
monar asociada al favipiravir. Lacidipina ofrece más beneficios terapéuticos que el
TPP en el tratamiento de la lesión pulmonar oxidativa causada por altas dosis de
favipiravir.
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Yamazaki S, Suzuki T, Sayama M, Nakada T-a, Igari H, Ishii I. Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19. J Infect Chemother 2021; 27(2): 390-392. https://doi. org/10.1016/j.jiac.2020.12.021
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Dogan E, Alkan-Çeviker S, Vurucu S, Sener A, Yüksel B, Gönlügür U, Simsek T, Hakan Ulusoy M. Investigation of the frequency of adverse effects in patients treated with favipiravir as SARS-CoV-2 treatment. Klimik Dergisi/Klimik J 2021; 34(2): 95-98. https://doi.org/10.36519/kd.2021.3563
Hayden FG, Shindo N. Influenza virus polymerase inhibitors in clinical development. Curr Opin Infect Dis 2019; 32(2): 176-186. https://doi.org/10.1097/qco.0000000000000532
Kara A, Yakut S, Caglayan C, Atçalı T, Ulucan A, Kandemir FM. Evaluation of the toxicological effects of favipiravir (T-705) on liver and kidney in rats: biochemical and histopathological approach. Drug Chem Toxicol 2022; 46(3): 546-556. https://doi. org/10.1080/01480545.2022.2066116
McCormack PL, Wagstaff AJ. Lacidipine. Drugs 2003; 63(21): 2327-2356. https://doi.org/10.2165/00003495-200363210-00008
Sai Chebrolu T, Kumar L, Verma R. Lacidipine: review of analytical methods developed for pharmaceutical dosage forms and biological fluids. Bioanalysis 2021; 13(12):1011-1024. https://doi.org/10.4155/bio-2021-0024
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Publicado
2024-02-15
Cómo citar
Elma, B., Suleyman, B., Mammadov, R., Yavuzer, B., Unver, E., Altuner , D., Coban, T. A., Mokhtare, B., & Suleyman , H. (2024). Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.: Toxicidad pulmonar asociada a altas dosis de favipiravir y opciones de tratamiento: Evaluación bioquímica e histopatológica. Investigación Clínica, 65(1), 83-98. https://doi.org/10.54817/IC.v65n1a08
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