ABSTRACT
The administration of the antilipolytic agents sodium nicotinate (1 mmole/kg i.p.) or sodium 5-methylpyrazole-3-carboxylate (0.5 or 1.0 mmole/kg i.p.) to alloxan-diabetic rats produced a significant reduction in the plasma concentration of free fatty acids and a slight reduction in blood glucose concentration. The concentrations in the freeze-clamped heart of citrate , acetyl CoA, Glucose-6-phosphate and fructose-6-phosphate were increased in untreated alloxan-diabetic rats relative to normoglycaemic controls. Treatment of alloxan-diabetic rats with the antilipolytic agents or insulin (60 U/kg i.p.) lowered these increased concentrations of metabolites in the heart. Treatment of the diabetic rats with the antilipolytic agents also produced an increase in the activity of pyruvate dehydrogenase in heart, but only treatment with 5-methylpyrazole-3-carboxylate had a significant effect on the activity of the enzyme in freeze-clamped soleus muscle.
Subject(s)
Carbohydrate Metabolism , Diabetes Mellitus, Experimental/metabolism , Muscles/metabolism , Nicotinic Acids/pharmacology , Pyrazoles/pharmacology , Alloxan , Animals , Male , Myocardium/metabolism , Pyruvate Dehydrogenase Complex/metabolism , Rats , Rats, Inbred StrainsABSTRACT
A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.
