Dose-dependent Oxidative Damage of Molnupiravir (Antiviral Drug for Treatment of COVID-19) in Lung, Liver, Heart, and Kidney Tissues in Rats

Abstract

Molnupiravir (MOL) is an orally absorbed prodrug of the ribonucleoside analogue N-hydroxycytidine, which has in vitro activity against several coronaviruses, including SARS-CoV-1 and 2. It remains to be seen whether long term MOL has serious side effects. The side effects of MOL, which was the first to be allowed for oral use during the pandemic process, are not yet fully known. In this study, it was aimed to investigate the the mechanisms of possible dose-dependent damage on liver, lung, heart, and kidney tissues. Fourty male Wistar albino rats were separated into four groups as Control, MOL10, MOL100, MOL1000. For five days, MOL (10-100-1000 mg/kg/day) was administered by oral gavaj. At the end of the five days rats were sacrificed and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels in serum were measured. Collected tissues (liver, lung, heart, and kidney) were evaluated to the malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant state (TAS), and total oxidant state (TOS), and oxidative stress indexes (OSI) were calculated. MOL administration showed significant improvement in liver, heart, and kidney in rats (p<0.05). SOD activities which were decreased in the MOL group, while MDA level increased in the MOL groups compared to the control group in all tissue (p<0.05). ALT was increased in the MOL group compared to the control group (p<0.05). Increase of TOS and OSI is statistically significant, but TAS was decreased in the MOL group compared to the control group (p<0.05). MOL used in virus treatment is dose-dependently effective on the oxidant/antioxidant system in tissues. For this reason, the use of antioxidants may be beneficial to reduce tissue damage that may occur in the use of MOL.