Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity

Darwish, Mostafa A.; Abo-Youssef, Amira M.; Khalaf, Marwa M.; Abo-Saif, Ali A.; Saleh, Ibrahim G.; Abdelghany, Tamer M.

doi:10.1016/j.toxlet.2018.03.023

Cited by 22 publications

(13 citation statements)

References 55 publications

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“…Similar to erastin, depletion of GSH along with the inactivation of GPxs was the underlying mechanism of action for cisplatin. In recent years, several studies [49][50][51][52][53][54][55] found the nephroprotective effects of PD and its aglycone and resveratrol, against cisplatin-induced oxidative stress and inflammation. However, their effects on inhibiting ferroptosis have only recently been reported in myocardial ischemia-reperfusion injury and intracerebral hemorrhage models [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Zhou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 μM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc− inhibitor erastin (10 μM), and the effect of the 40 μM dose of PD was more obvious than that of ferrostatin-1 (1 μM) and deferoxamine (DFO, 100 μM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc−-GSH-GPx4 axis and iron metabolism.

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Section: Discussionmentioning

confidence: 99%

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Zhou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Most of the GE effects are attributed to its rich composition of polyphenols, from which resveratrol is the most abundant and of high importance [48]. Resveratrol was previously linked to a better outcome in CIS-treated animals and is a potent antioxidant [15]. Besides its beneficial effects, resveratrol has also been reported as having pro-oxidant and cytotoxic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Of the numerous compounds with theorized nephroprotective effects, resveratrol and polyphenols such as phenolic acids present the most promise [15]. In vivo experimental studies have provided evidence of the nephroprotective effect of resveratrol (a major component in grape juice) on the toxicity induced by drugs or toxins (gentamicin, cyclosporine, cisplatin, arsenic trioxide).…”

Section: Introductionmentioning

confidence: 99%

Paradoxical Effect of Grape Pomace Extract on Cisplatin-Induced Acute Kidney Injury in Rats

Neag

Mitre

et al. 2019

Pharmaceutics

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Cisplatin is one of the most used drugs in the therapy of different types of cancer. However, its use is limited by nephrotoxicity. This study investigated the effects of a commercially available grape pomace extract (GE) from Vitis vinifera on cisplatin-induced kidney toxicity in rats. Sixty-four male Wistar albino rats were randomly divided into eight groups. Groups 1–3 were controls, receiving 0.9% saline and doses 1 and 2 of GE respectively. Cisplatin was given to groups 4–8. Two groups received pretreatment with GE, while another two groups received pre- and post-treatment with GE. Blood samples were collected and all animals sacrificed. Kidneys were harvested for histopathological analysis. GE significantly increased blood creatinine and urea levels, the severity of kidney histopathological damage, and mortality in all cisplatin groups, except for group 7 which received pre- and post-treatment with a low dose of GE. Renal toxicity was determined by mortality and severe histopathological renal lesions. Additionally, the serum total antioxidant capacity (TAC) was not significantly modified in the treated groups compared to the control. These results indicate that the GE did not have a protective effect on cisplatin-induced nephrotoxicity; on the contrary, GE accentuated the toxic effect of cisplatin.

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“…However, resveratrol has been shown to protect against cisplatin-induced nephrotoxicity [137,138,139], gonadotoxicity [140,141,142], and ototoxicity [143,144,145]. Pretreatment with resveratrol did not significantly alter the plasma level of cisplatin; however, it lowered its urinary concentration and its accumulation in the kidneys, which may explain its protective effects [146].…”

Section: Other Cardiotoxic Cancer Treatmentsmentioning

confidence: 99%

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

2019

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Cardio-oncology is a clinical/scientific discipline which aims to prevent and/or treat cardiovascular diseases in cancer patients. Although a large number of cancer treatments are known to cause cardiovascular toxicity, they are still widely used because they are highly effective. Unfortunately, therapeutic interventions to prevent and/or treat cancer treatment-induced cardiovascular toxicity have not been established yet. A major challenge for such interventions is to protect the cardiovascular system without compromising the therapeutic benefit of anticancer medications. Intriguingly, the polyphenolic natural compound resveratrol and its analogs have been shown in preclinical studies to protect against cancer treatment-induced cardiovascular toxicity. They have also been shown to possess significant anticancer properties on their own, and to enhance the anticancer effect of other cancer treatments. Thus, they hold significant promise to protect the cardiovascular system and fight the cancer at the same time. In this review, we will discuss the current knowledge regarding the cardio-protective and the anticancer properties of resveratrol and its analogs. Thereafter, we will discuss the challenges that face the clinical application of these agents. To conclude, we will highlight important gaps of knowledge and future research directions to accelerate the translation of these exciting preclinical findings to cancer patient care.

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Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity

Cited by 22 publications

References 55 publications

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Paradoxical Effect of Grape Pomace Extract on Cisplatin-Induced Acute Kidney Injury in Rats

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

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