Abstract

ELMA, Bekir et al. Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation. Invest. clín [online]. 2024, vol.65, n.1, pp.83-98.  Epub Mar 12, 2024. ISSN 0535-5133.  https://doi.org/10.54817/ic.v65n1a08.

Favipiravir is a broad-spectrum antiviral drug that is a viral RNA- dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidipine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Lacidipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathione), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopathologically examined. The systemic administration of high doses of favipiravir increased oxidant levels and decreased antioxidant levels in the lung tissue of rats.

In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mitigating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine administration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against favipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.

Keywords : Favipiravir; lacidipine; thiamine pyrophosphate; adenosine triphosphate; oxidative stress.

        · abstract in Spanish     · text in English     · English ( pdf )