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.
Highlights
Doxorubicin (DXR) is widely used as an efficient chemotherapeutic agent for different cancers (Minotti et al, 2004; An et al, 2017)
MO, USA), DXR was purchased from a local pharmacy in Riyadh (KSA), and the marketed N-Resv was purchased from Lipolife (Drakes Lane Industrial Estate, Drakes Lane, (UNited Kingdom), which was characterized as (Resv encapsulated in liposomes with particle size = 200 nm) by the manufacturer company
Oxidative stress markers were measured to evaluate the antioxidant properties of Card, Resv, N-Resv, and their combinations against DXR nephrotoxicity
Summary
Doxorubicin (DXR) is widely used as an efficient chemotherapeutic agent for different cancers (Minotti et al, 2004; An et al, 2017). DXR exerts its pharmacological anticancer actions by targeting and Renoprotective Effect of Nano-Resveratrol intercalating DNA of rapidly dividing tumor cells, causing cellcycle blockage in the G2 phase (Attia and Bakheet 2013). The exact molecular mechanisms of DXR-induced toxicity are not fully described; the most acceptable theory attributed to its toxicity is the initiation of oxidative stress (Korga et al, 2012). EL-Sheikh and others investigated the mechanisms underlying DXR nephrotoxicity, focusing on the role of oxidative stress and apoptosis (El-Sheikh et al, 2012). Doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXRinduced renal damage until now
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