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

Abstract

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.

Scientific Papers and Patents on Substances with Unproven Effects. Part 2

“…It has become a usual practice to disregard published criticism in spite of personal communications and debates at conferences. Apparently, certain scientists make use of critical comments without citing them, or just continue publications disregarding the criticism [61,204]. The same scientists continue working sometimes in cooperation with renowned researchers, while it is possible that some later reports are more reliable than earlier ones.…”

“…In these experiments, the ability of serum to induce accumulation of cholesterol in cultured cells was interpreted as an indicator of atherogenicity [1,58,59]. The reliability of these experiments has been questioned; however, the publication series has been continued without references to the published criticism [60,61]. In the Russianlanguage literature, PhE are promoted by misquoting of foreign literature; examples are shown in a study [60].…”

Soy phytoestrogens: hormonal activity and impact on the reproductive system

“…The results and conclusions of these experiments have been questioned; however, the publication series has been continued without references to comments [56,57]. PhE were sometimes promoted by means of misquoting [56].…”

“…The results and conclusions of these experiments have been questioned; however, the publication series has been continued without references to comments [56,57]. PhE were sometimes promoted by means of misquoting [56]. For example, in the original: "These compounds seem to be cancer protective… With regard to prostate and colon cancer… Mìžnarodnij endokrinologìčnij žurnal, ISSN 2224-0721 (print), ISSN 2307-1427 (online) Огляд літератури /Literature Review/ the epidemiological data related to phytoestrogens are still very limited" [58] and in another cited source: "Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers" [59].…”

On the use of carnosine and antioxidants: a letter from Russia

“…Some generalizations regarding the oxidants/antioxidants balance, attempting to present it as universal biological concept, seem to be oversimplifications. The problem consists of several partly interrelated topics: Antioxidants and cancer [ 23 ], wine, ethanol and cardiovascular risk [ 28 , 32 ], radiation protection [ 33 ], lens transparency and cataract [ 5 , 11 ], flavonoids, healthy aging, menopause, atherosclerosis prevention [ 34 ], antioxidants, carnosine and diseases of the nervous system [ 22 , 35 - 37 ], etc. Indications to the use of particular substances are questionable.…”