Effects of Remdesivir on Liver Enzymes, Oxidative Stress and Liver Histopathology in Rats

Abstract

<i>Background & Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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: This study identified Remdesivir-induced liver toxicity and oxidative stress alterations in rats, underscoring the need for careful liver function monitoring, especially in patients with hepatic dysfunction. The findings recommend caution in using Remdesivir as a first-line treatment in such cases, and further studies are required to validate these effects and explore broader clinical implications.