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

• DOI: 10.3389/fphar.2022.826908
• Publication Date: 2022-02-25T05:22:36Z
• Authors: Ahlam M. Alhusaini; Laila M. Fadda; Abeer M. Alanazi; Wedad S. Sarawi; Hatun A. Alomar; Hanaa M. Ali; Iman H. Hasan; Rehab Ahmed Ali
• Keywords: Clinical Biochemistry; renal damage; RM1-950; nano-resveratrol; Kidney; doxorubicin; Pathology and Forensic Medicine; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Health Sciences; Chemotherapy; Mechanisms and Renoprotective Strategies for Cisplatin Nephrotoxicity; Nephrotoxicity; Internal medicine; Pharmacology; 0303 health sciences; Toxicity; Role of Paraoxonase Enzymes in Atherosclerosis and Oxidative Stress; Life Sciences; Cardiotoxicity of Cancer Treatments; 3. Good health; Chemistry; Blood urea nitrogen; beclin-1; Doxorubicin; Resveratrol; Creatinine; mTOR; Medicine; Therapeutics. Pharmacology; Cardiology and Cardiovascular Medicine

Background: Although doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now.Aim: This work aims at examining 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 1 week before the 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 the 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.