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The pseudoginsenoside F11 ameliorates cisplatin-induced nephrotoxicity without compromising its anti-tumor activity in vivo.

ABSTRACT: The clinical use of cisplatin was severely limited by its associated nephrotoxicity. In this study, we investigated whether the pseudoginsenoside F11 had protective effects against cisplatin-induced nephrotoxicity. To clarify it, one in vivo model of cisplatin-induced acute renal failure was performed. The results showed that pretreatment with F11 reduced cisplatin-elevated blood urea nitrogen and creatinine levels, as well as ameliorated the histophathological damage. Further studies showed that F11 could suppress P53 activation, inverse the ratio of Bax/Bcl2 and the anti-oxidative and free radical levels induced by cisplatin, which in turn inhibited tubular cell apoptosis. Importantly, F11 enhanced rather than inhibited the anti-tumor activity of cispaltin in murine melanoma and Lewis lung cancer xenograft tumor models. Our findings suggested that administering F11 with cisplatin might alleviate the associated nephrotoxicity without compromising its therapeutic efficiency. This finding provides a novel potential strategy in the clinical treatment of cancer.

SUBMITTER: Wang H

PROVIDER: S-EPMC4023132 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties.

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Dichloroacetate (DCA) prevents cisplatin-induced nephrotoxicity without compromising its anti-cancer properties.

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Dichloroacetate (DCA) prevents cisplatin-induced nephrotoxicity without compromising its anti-cancer properties.

Project description:The aim of this study was to compare the transcriptional changes that occur in the kidneys of mice administered cisplatin or DCA, or both, by RNA-seq.

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Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity.

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5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

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| S-EPMC3855642 | biostudies-literature

Catalpol-Induced AMPK Activation Alleviates Cisplatin-Induced Nephrotoxicity through the Mitochondrial-Dependent Pathway without Compromising Its Anticancer Properties.

Project description:Nephrotoxicity is a common complication of cisplatin chemotherapy and, thus, limits the clinical application of cisplatin. In this work, the effects of catalpol (CAT), a bioactive ingredient extracted from Rehmannia glutinosa, on cisplatin-induced nephrotoxicity and antitumor efficacy were comprehensively investigated. Specifically, the protective effect of CAT on cisplatin-induced injury was explored in mice and HK-2 cells. In vivo, CAT administration strikingly suppressed cisplatin-induced renal dysfunction, morphology damage, apoptosis, and inflammation. In vitro, CAT induced activation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), improved mitochondrial function, and decreased generation of cellular reactive oxygen species (ROS), leading to a reduction in inflammation and apoptosis, which ultimately protected from cisplatin-induced injury. However, the beneficial effects of CAT were mostly blocked by coincubation with compound C. Furthermore, molecular docking results indicated that CAT had a higher affinity for AMPK than other AMPK activators such as danthron, phenformin, and metformin. Importantly, CAT possessed the ability to reverse drug resistance without compromising the antitumor properties of cisplatin. These findings suggest that CAT exerts positive effects against cisplatin-induced renal injury through reversing drug resistance via the mitochondrial-dependent pathway without affecting the anticancer activity of cisplatin.

| S-EPMC7826214 | biostudies-literature

Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-09 | GSE179247 | GEO

Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney_Tumor]

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Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney]

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Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity.

Project description:BackgroundTraditional Siddha Medicine advises using metal-based formulations to treat cancers. In the case of any toxicities during the therapy, Siddha physicians use Vernonia cinerea (VC) whole plant kashayam (crude aqueous extract-CAE) to reverse the toxic effects.AimTo evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin.Materials and methodsCisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated.ResultCAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin.ConclusionCAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.

| S-EPMC8116717 | biostudies-literature

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