Effects of Remdesivir on liver enzymes, oxidative stress and Liver histopathology in rats

Abstract Background & Aims: Remdesivir (REM) has been widely used to treat subjects affected by COVID-19 due to its broad-spectrum activity. The aim was to assess the REM effect on liver histopathology, enzymes, and alterations in oxidative stress markers.Methods Forty-eight Wistar rats were separated into eight groups as follows: Group A (Control) received normal saline intraperitoneally (IP) for 10 days; Group B (Low-dose REM) received REM (2.8 mg/kg for the first day and 1.4 mg/kg for days 2 to 10, IP); Group C (High-dose REM) received REM (8.5 mg/kg IP for the first 17 days and days 2 to 10); Group D (High-dose REM + DEX (Dexamethasone) + HEP (Heparin) received DEX (7 mg/kg intramuscularly for 10 days) and HEP (333 IU/kg subcutaneously on the first day and 250 IU/kg subcutaneously every 12 hours from day 2 to day 10); Group E (High-dose REM + DEX); Group F (High-dose REM + HEP); Group G (DEX); Group H (HEP). For statistical analysis, non-parametric tests (Kruskal-Wallis H and Mann-Whitney U) were used for pathological lesions (semi-quantitative data) between the different groups, and a p < 0.05 was considered significant.Results There were mild to severe pathological changes in the treated groups, including cell swelling, vascular congestion. Also, the D and G groups showed similar pathological lesions, which were more severe than in other treated groups with a significant difference (p < 0.05).Conclusions Remdesivir causes hepatic toxicity and alterations in oxidative stress markers, and therefore monitoring is required during treatment.