Biochemical and histopathological evaluation of systemic and ocular toxicity of favipiravir in rats

Abstract

Purpose: Favipiravir (FAV) used against COVID-19 is an antiviral drug that causes adverse reactions, such as hyperuricaemia, liver damage, and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of FAV in rats, for the first time.Materials and methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/d favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs. 4.82 ± 1.40 µmol/mL), IL-1β (2.52 ± 1.14 vs. 6.67 ± 1.99 pg/mL), and TNF-α levels (3.28 ± 1.42 vs. 8.53 ± 3.06 pg/mL) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs. 2.50 ± 0.98 nmol/mL) and SOD (13.63 ± 3.43 vs. 3.81 ± 1.43 U/mL) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusions: FAV can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose.

Keywords:

• Conjunctival and scleral toxicity
• favipiravir
• IL-1β
• MDA
• tGSH
• TNF-α

Acknowledgments

None.

Disclosure statement

The authors have no conflicts of interest to declare.

Authorship contribution

Conceptualization (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Data Curation (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Formal Analysis (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Funding Acquisition (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Investigation (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Methodology (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Project Administration (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Resource (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Supervision (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Writing (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS); Review & Editing (DÖ, FÖ, RM, MA, FA, AAA, MK, DA, HS).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.