The Effect of Remdesivir on Renal Sirt-1 Expression, Histopathology, and Renal Function-Related Biochemical Factors in male rats

Abstract

Remdesivir is a nucleoside analog and a viral RNA-dependent RNA polymerase inhibitor approved for the treatment of COVID-19 under emergency use authorization. On the other hand, since corticosteroid drugs such as dexamethasone and anticoagulants such as heparin are a constant part of the treatment protocol for patients with covid-19, Therefore, in the current study, the effect of remdesivir along with heparin and dexamethasone was investigated in order to investigate their individual and combined effects on kidney damage and the expression of one of the most important cellular protective proteins, renal sirtuin-1. The main aim of this study is to investigate the effect of remdesivir on biochemical factors related to kidney function, histopathological changes of kidney tissue and the expression level of sirtuin-1 protein in rat kidney tissue. Materials and Methods: 48 male rats were randomly divided into 8 groups of 6 (control, Remlow,Remhigh Rem+Dexa+Hep,Rem+Dex,Rem+Hep, Dexa,Hep) based on the administration of Rem or Dexa or hep. The duration of the prescriptions was for 10 days. The amount of kidney Sirt-1 gene expression was measured by real-time PCR method and the amount of serum urea and creatinin was done using an autoanalyzer. At the end of the course, biochemical factors were measured from the serum sample and molecular studies and Histopathology was performed on kidney tissues. Results: The renal expression of sirtuin-1 in the (Rem+Dex+Hep), (Rem+Dex), Rem+Hep, (Rem) groups was significantly lower than the control group (p<0.05). The amount of serum urea in the group (Rem+Dex+Hep) compared to the, (Dex), (Hep), (Rem) and also the amount of serum urea in the group (Rem + Hep) and the group (Rem+Dex) increased significantly compared to the control and Dex groups (p<0.05). The amount of serum creatinine in the groups (Rem+Dex+Hep), (Rem+Dex), (Rem+Hep), (Rem) showed a significant increase compared to the control group (p<0.05). The amount of renal tissue damage (TID) in the groups receiving (Rem+Dex+Hep) compared to the (Dex), (Rem), (Rem+Hep); Also, the amount of tissue damage in the (Rem+Dex) group compared to the (Rem) group; and in the (Rem+Hep) group compared to the (Rem) and (Hep) groups are significantly (p<0.05) higher than the ( control). Also, no significant difference (p<0.05) was found between the evaluated factors in terms of high and low doses of remdesivir.