Bioflavonoid Quercetin Inhibits Mitosis and Apoptosis of Glomerular Cells in Vitro and in Vivo

doi:10.1006/bbrc.2000.4016

Biochemical and Biophysical Research Communications

Volume 279, Issue 2, 20 December 2000, Pages 629-634

https://doi.org/10.1006/bbrc.2000.4016 Get rights and content

Abstract

Bioflavonoids have been regarded as therapeutic agents for a wide range of disease including inflammation. In this report, we investigated effects of bioflavonoid quercetin on mitosis and apoptosis of glomerular cells in vitro and in vivo. Serum-stimulated rat mesangial cells were treated with or without quercetin, and total cell number, percentages of mitotic cells, and incorporation of [³H]-thymidine were evaluated. All three assays showed that mitogenic activity of mesangial cells was markedly attenuated by quercetin. To examine the effect of quercetin on apoptosis, mesangial cells were pretreated with or without quercetin and stimulated by hydrogen peroxide or tumor necrosis factor-α. Hoechst staining and DNA ladder assay showed that both apoptotic responses were dramatically inhibited by quercetin. We further investigated effects of quercetin on in vivo mitosis and apoptosis of glomerular cells. Rats were administered with or without quercetin intraperitoneally, and nephrotoxic serum nephritis was induced. Immunohistochemical analyses showed that treatment with quercetin significantly reduced the number of proliferating cell nuclear antigen (+) cells and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (+) cells in the glomerulus. These data suggested that quercetin has the potential for inhibiting mitosis and apoptosis of glomerular cells both in vitro and in vivo.

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Oxidative stress has been implicated in tumorigenic, cardiovascular, neuro-, and age-related degenerative changes. Antioxidants minimize the oxidative damage through neutralization of reactive oxygen species (ROS) and other causative agents. Ever since the emergence of COVID-19, plant-derived antioxidants have received enormous attention, particularly in the Indian subcontinent. Quercetin (QCT), a bio-flavonoid, exists in the glycosylated form in fruits, berries and vegetables. The antioxidant potential of QCT analogs relates to the number of free hydroxyl groups in their structure. Despite presence of these groups, QCT exhibits substantial hydrophobicity. Formulation scientists have tested nanotechnology-based approaches for its improved solubilization and delivery to the intended site of action. By the virtue of its hydrophobicity, QCT gets encapsulated in nanocarriers carrying hydrophobic domains. Apart from passive accumulation, active uptake of such formulations into the target cells can be facilitated through well-studied functionalization strategies. In this review, we have discussed the approaches of improving solubilization and bioavailability of QCT with the use of nanoformulations.
Beneficial roles of honey polyphenols against some human degenerative diseases: A review
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Honey contains many active constituents and antioxidants such as polyphenols. Polyphenols are phytochemicals, a generic term for the several thousand plant-based molecules with antioxidant properties. Many in vitro studies in human cell cultures as well as many animal studies confirm the protective effect of polyphenols on a number of diseases such as cardiovascular diseases (CVD), diabetes, cancer, neurodegenerative diseases, pulmonary diseases, liver diseases and so on. Nevertheless, it is challenging to identify the specific biological mechanism underlying individual polyphenols and to determine how polyphenols impact human health. To date, several studies have attempted to elucidate the molecular pathway for specific polyphenols acting against particular diseases. In this review, we report on the various polyphenols present in different types of honey according to their classification, source, and specific functions and discuss several of the honey polyphenols with the most therapeutic potential to exert an effect on the various pathologies of some major diseases including CVD, diabetes, cancer, and neurodegenerative diseases.
The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats
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QUE is a natural flavonoid in many fruits and vegetables. Several epidemiological and experimental have studies reported that these molecules are effective antioxidants, anti-inflammatories, anti-apaptotic, anti-thrombotics, and anti-ischemics, and are anti-mutagenic, anti-cancer, anti-angiogenic, anti-proliferative, and anti-viral [6–11]. In experimental studies performed in several models of cancer toxicity caused by anticancer agents, QEU was reported to prevent this toxicity [12].
Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP’s side effects. This study aimed to investigate the protective effect of quercetin (QUE) on CYP-induced lung toxicity in rats using histologic and biochemical methods.
In the study, 50 male Sprague-Dawley rats weighing 220–250 g were used. There were 4 experimental groups and 1 control group. Group I is the control group, which was given only intragastric (i.g.) solvent (corn oil) for 7 days. Group II was given i.g. corn oil for 7 days as a placebo, and a single dose of intraperitoneal (i.p.) CYP (200 mg/kg) was given on day 7. Groups III and IV, respectively, were given QUE in doses of 50 and 100 mg/kg, dissolved in corn oil, and administered i.g. for 7 days. In addition, a single dose of CYP (200 mg/kg, i.p.) was administered on the 7th day of study. In Group V, a 100 mg/kg dose of QUE was given to rats i.g. for 7 days. On the 8th day of the experiment, all groups of rats’ blood and lung tissue samples were collected for analysis of oxidative stress parameters and histopathological examinations.
In the biochemical result (although oxidative parameters were increased in favor of tissue damage) QUE administration revealed attenuated CYP toxicity in the rats ‘lungs. In histologic analysis, QUE prevented the CYP-mediated tissue damage and the increase in mast-cell densities in the rats’ lung tissues.
The results of the present study have revealed that QUE provides a possible protective effect by inhibiting ROS and mast cell degranulation in induced lung damage.
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The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function
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Citation Excerpt :
One group was treated with the control vehicle and the other group with 50 mg/kg/day quercetin i.p, for 14 days. The choice of the experimental model and conditions were based on the following elements: the in vitro experiments were performed on a rat-derived cell line; and the Sprague–Dawley breed has been commonly used to study quercetin effects and pharmacokinetics (Ishikawa and Kitamura, 2000; Kinaci et al., 2012; Park et al., 2010; Piantelli et al., 2006). On the last day of treatment, each rat received 185 kBq [125I]-NaI i.p., and thyroid radioiodine uptake was evaluated after 24 h.
Quercetin is the most abundant flavonoid present in a broad range of fruit and vegetables. Furthermore, quercetin is available as dietary supplements that are based on its antioxidant, antiproliferative and anti-inflammatory properties. However, concerns have been raised about the potential toxic effects of excessive intake of quercetin, and several studies have demonstrated that flavonoids, included quercetin, can interfere with thyroid function. In a previous report, we showed that quercetin inhibits thyroid-cell growth and iodide uptake. The latter effect was associated with down-regulation of sodium/iodide symporter gene expression. In the present study, we have evaluated the effects of quercetin on the expression of other thyroid-restricted genes, and we show that quercetin decreases the expression of the thyrotropin receptor, thyroid peroxidase and thyroglobulin genes. We further investigated the inhibitory effects of quercetin on thyroid function in vivo through evaluation of radioiodine uptake in the Sprague–Dawley rat, which was significantly decreased after 14 days of quercetin treatment. These data confirm that quercetin can act as a thyroid disruptor, and they suggest that caution is needed in its supplemental and therapeutic use.
Evidence of apoptosis in some cell types due to pentachlorophenol (PCP) in Heteropneustes fossilis
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The study aimed to clarify the role of apoptosis in pentachlorophenol (PCP) induced testicular, ovarian and renal cell genotoxicity of Heteropneustes fossilis. It was further intended to find the target germ cell type and assess the cellular and nuclear damage. Treatment of PCP was used for multiduration on the germinal tissues and they were processed to detect structural changes by light and electron microscopic evaluation and kidney cells for subsequent detection of DNA fragmentation by agarose gel electrophoresis. Findings suggest functional and morphological changes in the tissues are due to apoptosis, as evidenced by some biochemical and cytological signs. Histological observation on germinal epithelium reveals cell suicidal symptoms such as vacuolization, liquefied regions in the cytoplasm of oocytes, margination of nuclei, clumping of chromatin, and compaction of cytoplasmic organelle. Biochemical manifestation concurrent to this, is; cleavage of kidney cell DNA into low molecular weight fragments confirming apoptosis. Subsequently, it is further cleaved into nucleosome size fragments or its multiples. Ultra-structural histopathology and DNA studies conclusively lead to the PCP induced apoptosis in the exposed cell types. Results further support the usefulness of this assay in the related studies and its feasibility in generating a base line data.

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¹: To whom correspondence should be addressed at Department of Medicine, University College Medical School, University College London, Jules Thorn Institute (7th Floor), Middlesex Hospital, Mortimer Street, London W1T 3AA, United Kingdom. Fax: +44-20-7636-9941. E-mail: [email protected].

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Regular ArticleBioflavonoid Quercetin Inhibits Mitosis and Apoptosis of Glomerular Cells in Vitro and in Vivo

Abstract

Fd. Chem. Toxic.

J. Biol. Chem.

Kidney Int.

Kidney Int. (Suppl.)

J. Biol. Chem.

Kidney Int.

Kidney Int.

J. Biol. Chem.

Kidney Int. (Suppl.)

Cancer Res.

Regular Article
Bioflavonoid Quercetin Inhibits Mitosis and Apoptosis of Glomerular Cells in Vitro and in Vivo