AUTHOR=Alhusaini Ahlam M. , Fadda Laila M. , Alanazi Abeer M. , Sarawi Wedad S. , Alomar Hatun A. , Ali Hanaa M. , Hasan Iman H. , Ali Rehab Ahmed 

TITLE=Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.826908

DOI=10.3389/fphar.2022.826908

ISSN=1663-9812

ABSTRACT=Background: Although doxorubicin (DXR) is one of the most used anticancer drug, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now. Aim: This work aims to examine the potential impact of Nano-resveratrol (N-Resv), native resveratrol (Resv) and their combination with carvedilol (Card) against DXR-induced renal toxicity in rats, and to investigate the mechanisms through which these antioxidants act to ameliorate DXR-nephrotoxicity. Method: DXR was administered to rats (2 mg/kg, i.p.) twice weekly over 5-weeks. The antioxidants in question were taken one week before DXR dose for 6 weeks. Results: DXR exhibited an elevation in serum urea, creatinine, renal lipid peroxide levels, endoglin expression, kidney injury molecule-1 (KIM-1) and beclin-1. On the other hand, renal podocin and mTOR expression and GSH levels were declined. In addition, DNA fragmentation was markedly increased in DXR administered group. Treatment with either Resv or N-Resv alone or in combination with Card ameliorated the previously measured parameters. Conclusion: N-Resv showed superior effectiveness relative to Resv in most of the measured parameters. Histopathological examination revealed amelioration of renal structural and cellular changes after DXR by Card and N-Resv, thus validating the previous biochemical and molecular results.