Lack of Effect of Glibenclamide, Chlorpropamide and Metformin on Plasma Cholesterol and HDL-Cholesterol in Non-Diabetic Rats

Abstract

Considerable evidence suggests that the incidence of arteriosclerotic coronary heart disease is positively related to plasma concentrations of total cholesterol and Low Density Lipoprotein cholesterol, but inversely related to High Density Lipoprotein (HDL)-cholesterol {Miller and Miller 1978). Non-insulin dependent maturity-onset diabetics show an increased incidence of coronary heart disease and reduced plasma HDL-cholesterol concentrations (Kennedy, Lappin, Lavery, Hadden, Weaver and Montgomery 1978;Reckless, Betteridge, Payne and Galton 1978). Treatment with tolbutamide or phenformin has been reported to aggravate cardiovascular lesions in some (Klimt 1977) but not all (CarlStrom 1977) studies, and it has been suggested that tolbutamide and glibenclamide may constitute an additional risk for these lesions by further lowering HDL-cholesterol concentrations (Calvert, Graham, Mannik, Wise and Yeates 1978). The present study investigates whether oral hypoglycaemic agents affect plasma cholesterol and HDL-cholesterol concentrations in non-diabetic rats. Materials and MethodsAdult male Sprague-Dawley rats were treated for 8 weeks with daily intraperitoneal injections of either glibenclamide (0.4 mg/kg), chlorpropamide (10 mg/kg) or metformin hydrochloride (60 mg/kg). These doses correspond to the maximum recommended clinical doses on a weight for weight basis. Controls received vehicle only (buffered saline). Blood samples (200 >i\) were taken from the cut tip of the tail at intervals throughout the study after an 18 h fast and 4 h after the last injection. Supernatants for HDL-cholesterol analysis were prepared by modification of the heparin-manganese technique (final concentrations 2 g/1 and 92 mmol/1 respectively). This modification produces values similar to the ultracentrifugal method (Ishikawa, McNeely, Steiner, Glueck, Mellies, Gartside and McMillin 1978). Total plasma cholesterol and HDL-cholesterol of the supernatant were measured by a fully enzymatic CHOD/PAP colorimetric method (Boehringer, Mannheim), incorporating EDTA (final concentration 10 mmol/1) into the reaction mixture for HDL-cholesterol (Steel, Koehler, Azar, Blaszkowski, Kuba and Dempsey 1976). Results and DiscussionStudies at the beginning and end of the 8 week period showed that glibenclamide and chlorpropamide significantly lowered plasma glucose concentrations for 4 to 5 h after injection. Metformin did not significantly alter plasma glucose. Body weight and food consumption were not significantly affected by the treatments. Plasma cholesterol, HDL-cholesterol and the total cholesterol: HDL-cholesterol ratio were not significantly altered by any of the treatments throughout the 8 week period of study (Fig. 1). These observations do not preclude the possibility that inordinately high doses or very long term therapy might influence these parameters, or that diabetic individuals may respond differently. 5 » O "of 1.5-O r-l .CO*. O £ (4 3 Jl I OS Fig. 1 Plasma concentrations of total cholesterol, HDLcholesterol and the total cholesterol: HDL...

Changes in Butyrylcholinesterase Activity and Serum Lipids after Oxprenolol and Glibenclamide Treatments in Non-diabetic Rats

“…According to George and Augusti, prolonged administration of GL (50 µg/kg daily, during 2 months) in normal rats, significantly decreased blood sugar, liver glycogen and protein, and significantly increased liver and serum lipids (e.g. triglyceride glycerol, total and free cholesterol) [33]. The triglyceride was more increased in the serum (35%) than in the liver (23%).…”