Impact of Remdesivir on the kidney and potential protective capacity of Granulocyte-Colony Stimulating Factor versus Bone Marrow Mesenchymal Stem Cells in adult male albino rats

Abstract

Background: Remdesivir is a novel broad spectrum antiviral drug previously used to treat Ebola. It is a pro-drug nucleoside with antiviral activity that is opposed to SARS-CoV-2 and coronavirus. Aim: Current research was planned to evaluate and compare the potential ameliorative impact of the hematopoietic-stem-cell mobilized by the granulocyte colony-stimulating factor (G-CSF) versus BM-MSC on the effect of novel antiviral remdesivir on the kidney. Materials and Methods: Rats divided into four groups: control group, Remdesivir treated group (20 mg/kg/day IV on the first day followed by 10 mg/kg/day for 6 days), Remdesivir + BM-MSCs group (3x10⁶ cells/ml of PKH26 labelled MSC) and Remedesivir+ Filgrastim group (70 μg/kg/day/5 days). At the end of the experiment, animals were anaesthetized and sacrificed. Both animal kidneys were excised for histological, immunohistochemistry, and electron microscopy studies. Biochemical and morphometric assessments had been performed. Results: Remdesivir caused distortion and degeneration of both the glomeruli and the renal tubules associated with Bowman's space widening. It greatly increased the deposition of collagen and enhanced the expression of caspase 3, IL-6, and TGF-β1. Ultrastructure changes were observed in the form of thickening of glomerular basement membrane, dilated basal plasma membrane infoldings of tubular epithelium and mitochondrial degeneration. Biochemically, decreased antioxidant enzymes, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) with increased serum urea and creatinine were also recorded. Both BM-MSCs and G-CSF improved histological structure and function of the kidney. Conclusion:Prescribing drugs such as remdesivir should be carried out with severe care. BM-MSCs and G-CSF are an efficient and ideal option to protect patients from irreversible kidney damage.

Histological Assessment of Remdesivir On kidney and Liver of Albino Rats in Different Doses And their Withdrawal

“…Also, a significant widening of Bowman's space with dilated renal tubules and an acidophilic cast in their lumen, combined with degeneration of the renal interstitium, left wide spaces in between renal tubules. These observations conform with the changes that are dose-related (26). Another investigation in rhesus monkeys found remdesivir-induced renal impairment at dosages of 5, 10, and 20 mg/kg per day for 7 days (27).…”