Pycnogenol Cytotoxicity in Pancreatic INS‐1E β cells Induced by Calcium Dysregulation

Viskupičová, Jana; Zizkova, Petronela; Račková, Lucia; Horáková, Ľubica

doi:10.1002/ptr.5894

Cited by 4 publications

(4 citation statements)

References 31 publications

(45 reference statements)

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“…Rat INS-1E insulinoma pancreatic β-cells were kindly provided by Prof. Claes Wollheim, University of Geneva) and were cultured in RPMI 1640 (11 mM glucose, Sigma Aldrich) supplemented with 100 U/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine, 1 mM Na pyruvate, 55 µM 2-mercaptoethanol, 10 mM HEPES, 1% non-essential amino acids, and 10% fetal bovine serum, pH 7.0-7.4. The cells were grown in a humidified incubator containing 5% CO 2 at 37 °C as described previously (Viskupicova et al, 2017).…”

Section: Cell Linesmentioning

confidence: 99%

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General toxicity assessment of the novel aldose reductase inhibitor cemtirestat

Prnová

Račková

Kovacikova

et al. 2019

Interdisciplinary Toxicology

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Cemtirestat, 3-mercapto-5H-[1,2,4]-triazino[5,6-b]indole-5-acetic acid was recently designed and patented as a highly selective and efficient aldose reductase inhibitor endowed with antioxidant activity. The aim of the present study was to assess the general toxicity of cemtirestat using in silico predictions, in vitro and in vivo assays. ProTox-II toxicity prediction software gave 17 “Inactive” outputs, a mild hepatotoxicity score (0.52 probability) along with a predicted LD50 of 1000 mg/kg. Five different cell lines were used including the immortalized mouse microglia BV-2, the primary human fibroblasts VH10, the insulinoma pancreatic β-cells INS-1E, the human colon cancer cells HCT116 and the human immortalized epithelial endometrial cell lines HIEEC. In contrast to the clinically used epalrestat, cemtirestat showed remarkably low cytotoxicity in several different cell culture viability tests such as MTT proliferation assay, neutral red uptake, BrdU incorporation, WST-1 proliferation assay and propidium iodide staining followed by flow cytometry. In a yeast spotting assay, the presence of cemtirestat in incubation of Saccaromyces cerevisiae at concentrations as high as 1000 µM did not affect cell growth rate significantly. In the 120-day repeated oral toxicity study in male Wistar rats with daily cemtirestat dose of 6.4 mg/kg, no significant behavioral alterations or toxicological manifestations were observed in clinical and pathological examinations or in hematological parameters. In summary, these results suggest that cemtirestat is a safe drug that can proceed beyond preclinical studies.

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Section: Cell Linesmentioning

confidence: 99%

“…Subsequently, 100 μl of 10% sodium dodecyl sulfate in HCl (0.01 M) was added and the cells were incubated at 37 °C overnight for complete dissolution of generated formazan. The absorbance was spectrophotometrically recorded at 570 nm using the reference 690 nm (Mrvova et al, 2015;Viskupicova et al, 2017).…”

Section: Mtt Viability Testmentioning

confidence: 99%

General toxicity assessment of the novel aldose reductase inhibitor cemtirestat

Prnová

Račková

Kovacikova

et al. 2019

Interdisciplinary Toxicology

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“…Pycnogenol ® (Pyc), or French maritime pine bark extract, is an extract from a plant bark known as Pinus pinaster (from class Pinopsida, order Pinales and family Pinaceae) 1 that has been studied for different purposes, such as the treatment of osteoarthritis, neuropsychiatric conditions, cardiovascular diseases, and dermato-cosmetic therapies. 2 Some of the most significant biological effects are: the protein-binding capacity, high structural mutability and function diversity. Also, the role of Pyc in the cellular antioxidant network, mediated by generegulated redox status, has been demonstrated.…”

Section: Overviewmentioning

confidence: 99%

Pycnogenol® (bark extract from pinus pinaster) uses in prevention and treatment of cardiopathies

et al. 2019

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Pycnogenol® (Pyc) is an extract from a plant bark known as Pinus pinaster. Some studies have shown that Pyc can prevent oxidative damage, inhibit inflammatory cytokines and be used in the treatment of metabolic syndrome. This study aimed to review the state of the art of Pyc in the treatment of cardiovascular disease. The keywords “pycnogenol” and “cardiopathy” were searched on the PubMed, Scopus, The Cochrane Library, Scielo and Bireme databases. Studies involving animals or with no relation to cardiological conditions were excluded. The findings in the literature point Pycnogenol® as a promising substance in the treatment of cardiovascular conditions, as well as in other medical situations. Some studies have showed benefits in reduction of antihypertensive drugs dose and collateral effects, better control of diabetes, and reduction of cardiovascular risk factors. However, these results were obtained from studies with small sample of patients, limited follow-up and important biases. Further studies such as larger clinical trials are needed to elucidate the real risk-benefit of Pycnogenol® on treatment of cardiovascular diseases.

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“…Recently, the natural extract Pycnogenol 1 , obtained from the outer bark of Pinus pinaster Ait. has gained attention for its antidiabetic properties (Viskupicova et al, 2017). Pycnogenol 1 is rich in polyphenolic compounds (standardized to 70 AE 5% procyanidins) and contains catechin, taxifolin, and cinnamic/ benzoic acid derivatives (Devaraj et al, 2002) that confer a digestive enzyme inhibitory activity, especially against aglucosidase and a-amylases.…”

Section: Discovery and Characterization Of Antidiabetic Agents Fromentioning

confidence: 99%

The role of mass spectrometry in studies of glycation processes and diabetes management

DaRonco

Crotti

Agostini

et al. 2018

Mass Spectrometry Reviews

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In the last decade, mass spectrometry has been widely employed in the study of diabetes. This was mainly due to the development of new, highly sensitive, and specific methods representing powerful tools to go deep into the biochemical and pathogenetic processes typical of the disease. The aim of this review is to give a panorama of the scientifically valid results obtained in this contest. The recent studies on glycation processes, in particular those devoted to the mechanism of production and to the reactivity of advanced glycation end products (AGEs, AGE peptides, glyoxal, methylglyoxal, dicarbonyl compounds) allowed to obtain a different view on short and long term complications of diabetes. These results have been employed in the research of effective markers and mass spectrometry represented a precious tool allowing the monitoring of diabetic nephropathy, cardiovascular complications, and gestational diabetes. The same approaches have been employed to monitor the non‐insulinic diabetes pharmacological treatments, as well as in the discovery and characterization of antidiabetic agents from natural products. © 2018 Wiley Periodicals, Inc. Mass Spec Rev 38:112–146, 2019.

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Pycnogenol Cytotoxicity in Pancreatic INS‐1E β cells Induced by Calcium Dysregulation

Cited by 4 publications

References 31 publications

General toxicity assessment of the novel aldose reductase inhibitor cemtirestat

General toxicity assessment of the novel aldose reductase inhibitor cemtirestat

Pycnogenol® (bark extract from pinus pinaster) uses in prevention and treatment of cardiopathies

The role of mass spectrometry in studies of glycation processes and diabetes management

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