Use of Cell Culture for Optimisation of Direct Antiatherogenic Therapy with Verapamil

Orekhov, Alexander N.; Pivovarova, E.M.; Sobenin, Igor A.; Yakushkin, V. V.; Tertov, V.V.

doi:10.2165/00003495-199200441-00020

Cited by 9 publications

(11 citation statements)

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“…Anti-atherogenic actions of different drugs and substances of plant origin were measured in the cell cultures [42][43][44][45]: if an agent induced lipid accumulation by the cultured cells it was deemed atherogenic and vice versa. As discussed previously however [38], if a pharmacological agent lowers the uptake of lipids by cells in a culture, it should be expected to increase the blood cholesterol level in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the endothelial dysfunction, one of the central events in the atherogenesis, is not reproduced in the cell monocultures. Nonetheless the cell cultures have been used in Russia since about 25 years [42,43,45,54] for testing of supposedly anti-atherogenic drugs and dietary supplements including phytoestrogens in support for their official registration.Acknowledgment …”

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confidence: 99%

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Concerns about Soy Cultivation: What is Known and What is not Known

Sv¹

2014

Journal of Nutrition and Health Sciences

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There is abundant literature suggesting medical use for phytoestrogen-containing products. There is also published evidence suggesting potentially negative consequences of phytoestrogens use for humans. Substantiation of both concepts appears questionable. Meanwhile, soy products are used liberally in the food also for infants and children. The concept discussed here is that it is not consistent to support soy use for estrogenic effects without concern for its impact on routine use as a foodstuff and livestock fodder. It is important for thorough independent studies to be done to answer these questions. Phytoestrogens are substances of plant origin that are structurally and functionally similar to estrogens. Among them, isoflavones and coumestans are the most extensively studied groups. Isoflavones are present in different edible plants, but are most abundant in soy [1][2][3]. Consumption of soy products has been associated with favorable health effects, but potentially adverse effects are underacknowledged [4]. Phytoestrogens are advertised as a natural alternative to estrogens for hormone replacement therapy during menopause [1]. Preclinical trials have demonstrated both genomic and non-genomic action of phytoestrogens including selective but weak binding to the estrogen receptors [5]. Some epidemiological studies suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal cardiovascular disease [6] and that phytoestrogens are significantly more effective than placebo in reducing the frequency of hot flashes [7]. Evidence in support of clinically relevant biological effects has been generally rated as insufficient or absent [5,[8][9][10][11][12][13][14]. A recent review concluded that in spite of increasing preclinical and clinical studies over the past decade, "appealing evidence is still lacking to support the overall positive risk-benefit profile of phytoestrogens" [15]. Then as now, the conventional menopausal hormone replacement therapy remains the only treatment that has consistently had a greater effect than placebo in controlled trials [16]. As evaluation of earlier works on enrichment the diet with soy products has failed to confirm favorable effects related to the cardiovascular system [17], doubts concerning phytoestrogens have recently increased. There is little evidence to support the hypothesis that phytoestrogens protect against menopausal osteoporosis, with published studies having no controls for confounding factors, the observations generally being of short duration [18,19]. In regard to osteoporosis, the latest review concluded that "evidence points to a lack of a protective role of soy isoflavones in the prevention of postmenopausal bone loss" [20], although in vitro and animal studies show some positive effect of isoflavones on bone which has not been clearly confirmed by long-term human trials [21]. There might be genetic differences in this regard, as equol producers seem to present a more positive response to isoflavone intervention ...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Concerns about Soy Cultivation: What is Known and What is not Known

Sv¹

2014

Journal of Nutrition and Health Sciences

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“…By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in vulnerable sites with the endothelial barrier damaged by hemodynamic forces or otherwise, within pre-existent vulnerable plaques -so as it happens in vivo in conditions of progressive atherosclerosis. This is the philosophical paradox apparently disregarded by the authors of [1][2][3][4][5][6][7][8][9][10][11][12][13]: the agents supposedly having an "anti-atherogenic" potency in a cell culture might reduce cholesterol uptake diffusely by entire cell populations contributing thereby to hypercholesterolemia. On the contrary, atherosclerosis is a focal disease, affecting primarily damaged sites of the vascular lining, which would be favored by hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

“…The large research series has become internationally known in the 1980s and continues until today [1][2][3][4][5][6][7][8][9][10][11][12][13]. In brief, cultures of smooth muscle or monocyte-derived cells have been used for evaluation of the ability of different substances to enhance or diminish cholesterol deposition in the cells, incubated with the serum from patients with atherosclerosis, which has been interpreted as anti-or pro-atherogenic action.…”

Section: Introductionmentioning

confidence: 99%

Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment

Jargin

2015

IJPPE

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The large research series has become internationally known in the 1980s and continues until today. Cultures of cultured or incubated smooth muscle cells or monocytes/macrophages were used for the measurement of capacities of substances to enhance or lower intracellular cholesterol deposition, which was interpreted as anti-or pro-atherogenic action. The LDL from patients with coronary atherosclerosis caused a 2-4 times elevation of cholesterol contents within the cultured cells. Incubation with sera or LDL from healthy subjects did not induce cholesterol accumulation. Various drugs and natural substances were found to possess pro-or anti-atherogenic potencies. Anti-atherogenic effect of different preparations of plant origin was reported: if an agent induced intracellular lipid accumulation it was regarded atherogenic and vice versa. However, if a pharmacological agent lowers the uptake of lipids by cells in a culture, it should be expected to increase the blood cholesterol level in vivo. It can be reasonably assumed that a drug, inhibiting cholesterol uptake by cultured cells, would elevate the blood cholesterol level in vivo. By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in sites with damaged endothelial barrier and vulnerable plaques. The agents supposedly having an anti-atherogenic potency in a cell culture might reduce cholesterol uptake diffusely by entire cell populations contributing thereby to hypercholesterolemia. On the contrary, atherosclerosis is a focal disease, affecting primarily damaged sites of the vascular lining, which would be favored by hypercholesterolemia.

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“…Furthermore, recommendations for practice were formulated on the basis of cell culture experiments [13], including drug dosage: “To decrease atherogenic potential of serum and to maintain it at a low level, verapamil should be administered at a dose of 40 mg 5 times daily with a 4- to 5-hour interval between doses.” [13] This recommendation should be seen within the scope of a broader question, whether data from cellular models may be used directly for clinical recommendations without clinical trials. Cellular systems in pharmacological research are essential for initial evaluation of drugs.…”

Section: Letter To the Editormentioning

confidence: 99%

Testing of serum atherogenicity in cell cultures: questionable data published

Jargin¹

2012

GMS German Medical Science; 10:Doc02; ISSN 1612-3174

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Use of Cell Culture for Optimisation of Direct Antiatherogenic Therapy with Verapamil

Cited by 9 publications

References 16 publications

Concerns about Soy Cultivation: What is Known and What is not Known

Concerns about Soy Cultivation: What is Known and What is not Known

Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment

Testing of serum atherogenicity in cell cultures: questionable data published

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