[The effect of dimethyl-(imidazol-1-yl) methanesulfonic acid on experimental atherogenesis in rabbits].

Abstract

The hypocholesterolemic and antiatherosclerotic activities of the new imidazole derivative dimethyl-(imidazole-1-yl) methanesulfonic acid (1273) were investigated in rabbits fed through a probe either cholesterol, 200 mg/kg body weight, suspended in sunflower seed oil or that supplemented by imidazole, 15 mg/kg body weight, or its derivative 1273, 30 mg/kg body weight. Total cholesterol showed an 8-fold increase in all rabbit groups as compared to that in the animals fed a routine laboratory chow. In the agent 1273-given animals, the aortic atherosclerotic lesion index (ALI) was 7.8%, which was 2.4 times lower that in hypercholesterolemic animals untreated with this agent or treated with imidazole. Concurrently with a decrease in the aortic ALI, the agent 1273 lowered the rabbit hepatic levels of free and esterified cholesterol. The experimental findings of cultured rabbit hepatocytes suggest that the agent 1273 reduces hepatic cholesterol levels by inhibiting the de novo cholesterol synthesis. In vitro studies on murine J774 macrophages have demonstrated that inhibition of cholesterol esterification in the vascular wall macrophages is one of the possible mechanisms responsible for the antiatherosclerotic activity of this derivative of imidazole.

• Authors: G S Dautova, V A Kosykh, V S Repin, R A Kamburg
• Journal: Eksperimental'naia i klinicheskaia farmakologiia (Eksp Klin Farmakol) 1994 Sep-Oct Vol. 57 Issue 5 Pg. 21-4 ISSN: 0869-2092 [Print] Russia (Federation)
• Vernacular Title: Vliianie dimetil-(imidazol-1-il) metansul'fonovoĭ kisloty na éksperimental'nyĭ aterogenez u krolikov.
• PMID: 7696897 (Publication Type: Comparative Study, English Abstract, Journal Article)

Chemical References

• Anticholesteremic Agents
• Imidazoles
• Mesylates

Topics

• Animals
• Anticholesteremic Agents (pharmacology, therapeutic use, toxicity)
• Arteriosclerosis (blood, drug therapy)
• Cell Line
• Cells, Cultured
• Diet, Atherogenic
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Hypercholesterolemia (blood, drug therapy)
• Imidazoles (pharmacology, therapeutic use, toxicity)
• Lethal Dose 50
• Liver (cytology, drug effects, metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Mesylates (pharmacology, therapeutic use, toxicity)
• Mice
• Rabbits
• Rats