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Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin

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TLDR
The data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells, and the exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.
Abstract
Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100–400 μM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10–25 μM and reaching a plateau between 50 and 100 μM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100–500 μM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 μM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

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The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells.

TL;DR: The modulation of iNOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in Chang Liver cells, via mechanisms likely to involve blockade of NF-kappaB activation and the resultant up-regulation of the pro-inflammatory genes.
Journal ArticleDOI

Silybin and silymarin - new effects and applications

TL;DR: This article aims to review critically literature published mainly within this millennium on the new and emerging applications of silymarin, the polyphenolic fraction from the seeds of Silybum marianum and its main component silybin, to suggest new mechanisms of its action.
Journal ArticleDOI

Chemotherapy and dietary phytochemical agents.

TL;DR: Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics.
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Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages

TL;DR: Results indicated that combinatorial treatment of L‐arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS‐induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX‐2 genes.
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The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy

TL;DR: Results suggest that nitric oxide and peroxynitrite are also involved in the neurotoxic effect of oxaliplatin and that rutin and quercetin can inhibit their effect in the spinal cord.
References
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Journal ArticleDOI

Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays

TL;DR: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation and is used to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
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Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.

TL;DR: Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men and showed an inverse relation with incidence of myocardial infarction.
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Hydroxyl radical scavenging activity of flavonoids

TL;DR: The scavenging activity of flavonoids decreases in the order: myricetin > quercetin> rhamnetin > morin > diosmetin > naringenin > apigenin > catechin > 5,7- dihydroxy -3′,4′,5′-trimethoxyflavone > robinin > kaempferol > flavone as discussed by the authors.
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Flavonoids as antioxidant agents: Importance of their interaction with biomembranes

TL;DR: The hypothesis will be discussed that flavonoid capacity to modify membrane-dependent processes, such as free-radical-induced membrane lipoperoxidation, is related not only to their structural characteristics but also to their ability to interact with and penetrate the lipid bilayers.
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