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

Abstract

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.

Bibliometric and visual analysis of nephrotoxicity research worldwide

“…Studies have reported that a combination of vancomycin and piperacillin-tazobactam could induce additive nephrotoxicity through routine creatinine evaluation, but it does not worsen the level of kidney injury molecular-1 biomarker, suggesting that kidney function should be considered by integrative evaluation ( Chang et al, 2022 ). Doxorubicin nephrotoxicity could be mitigated by nano-resveratrol through modulation of Beclin-1 and mammalian TOR ( Alhusaini et al, 2022 ). It could also be protected by pirfenidone and vitamin D through inhibition of c-Jun N-terminal kinase-1 and monocyte chemoattractant protein-1 pathways ( Hazem et al, 2022 ).…”

Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury

“…RES and L-RES groups: rats were treated with either RES or L-RES (20 mg/kg/day, p.o.) dissolved in 1% CMC ( Alhusaini et al 2022 ). for 14 days along with ISO.…”

Recent progress in nanotechnology-based drug carriers for resveratrol delivery

“…For example, the encapsulation of free RES into liposomes (Lip-RES) at 37 °C under light conditions improved its chemical stability and bioavailability, while also increasing RES uptake by white adipocytes by 25% (Zu et al., 2018 ). Lip-RES showed superior effectiveness relative to free RES in against DXR-induced renal toxicity in rats (Alhusaini et al., 2022 ). In addition, Lip-RES increased the uptake of RES by cardiomyocytes and thus significantly activated the maximum cellular respiratory capacity (Tsujioka et al., 2022 ).…”