Normocholesterolemic Rats Research Articles

Effect of lipoprotein on 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity in rat liver cell culture: Special suppressant effect of a lipoprotein isolated from hypercholesterolemic rat plasma

A significant advance in cell culture methodology has permitted an analysis of the regulation of liver cell cholesterol metabolism by lipoproteins. The effect of rat lipoproteins on the activity of the rate limiting enzyme in cholesterol biosynthesis, HMG CoA reductase, was studied in monolayer cultures of adult rat hepatic parenchymal cells. Lipoproteins isolated from normocholesterolemic rat plasma, including low density lipoprotein, did not suppress HMG CoA reductase activity. However, enzyme activity was profoundly suppressed by a cholesterol rich d < 1.063 lipoprotein(s) isolated from hyperlipemic rat plasma. This lipoprotein may regulate the suppression of endogenous hepatic cholesterol biosynthesis which occurs after cholesterol feeding.

Triparanol-induced desmosterol accumulation in clofibrate-effected hypocholesterolemia

Clofibrate-induced hypocholesterolemic rats accumulate triparanol-effected desmosterol (24-dehydrocholesterol) no differently than do triparanol-treated normocholesterolemic rats. Accordingly, these findings indicate that hepatic cholesterol biosynthesis proceeds essentially normally in clofibrate-induced hypocholesterolemic rats. Thus, clofibrate-induced hypocholesterolemia is not primarily due to a shutdown of hepatic cholesterol biosynthesis. This conclusion does not exclude the possibility that inhibition of hepatic cholesterol biosynthesis by clofibrate may contribute to some degree to the clofibrate-induced hypocholesterolemia.

Pharmacological Study of Hydroxy Bis-[2-(P-Chlorophenoxy)-Isobutyric Acid] Aluminium [I] the Effect of Hydroxy Bis-[2-(P-Chlorophenoxy)-Isobutyric Acid] Aluminium on Lipid Metabolism in Normal Rats

The hypolipidemic effect of alfibrate has been studied in normocholes-terolemic rats with clofibrate as a reference. At the dosage of 150 mg/kg, 29 % increase of liver weight was observed in the alfibrate group and 87 % increase in the clofibrate group. Daily administration of alfibrate (150 mg/kg) produced a significant decrease in serum cholesterol (5%) and triglycerides (15%), and liver cholesterol (12%) and triglycerides (23%) with no change in phospholipids and free fatty acids. Like clofibrate, alfibrate exerted a greater effect on lowering the triglyceride level than cholesterol in normocholesterolemic rats. The liver glycogen concentration and glucose tolerance in the alfibrate group were similar to that of control.

Studies on anti-hypercholesterolemic activity of Indanyl tetrazoles

Introduction: Clinically useful non-steroidal antihyperlipidemic drugs are now in the market for the treatment of patients suffering from hypercholesterolemia. Indan acids, which belong to non-steroidal aryl alkanoic acids class acids have been reported to possess varying degrees of cholesterol lowering activity. Keeping the above points in view exploration for better anti-hypercholesterolemic activity of indanyl tetrazole derivatives was undertaken. Methods: Five-week-old male albino Charles Foster rats (120± 10 g) for normocholesterolemic and seven-week-old rats (130±10g) for hypercholesterolemic studies were used. On the 0-day and 14th day, tail vein blood was drawn from the overnight fasted animals respectively. Biochemical measurements were carried out using biochemical kits (Span, India) and an automated biochemical analyzer (Vitros-250, Johnson and Johnson Co. USA). Results: The compound - V and VI exhibited almost same significant level of cholesterol lowering (p&lt;0.01) activity. On closer look its reveal that the compound-VI exhibit triglyceride lowering (p&lt;0.01) activity among the groups around 14 days of treatment on normocholesterolemic rats. Test compound- V (p&lt;0.05) and compound-VI (p&lt;0.001) have significant anti-hyper-cholesterolemic activity while clofibrate has no such activity on hypercholesterolemic rats. Conclusions: Indanyl tetrazole derivatives, 5-(62 -methoxyindan-12 -yl) methyltetrazole (V) and 5- (52 , 62 -dimethoxyindan-12 -yl) methyltetrazole (VI) were more promising than their analogs in respect to their anti-hypercholesterolemic activity. DOI: http://dx.doi.org/10.3126/joim.v32i3.4956 Journal of Institute of Medicine, December, 2010; 32:3 24-29

Effects of oestrone and 2-methoxymethyl-17α-methyl-oestradiol-3-methyl ether (P-5780) on cholesterol metabolism in normo- and hypercholesterolaemic rats

In vivo studies have been made on the effects of oestrone and 2-methoxymethyl-17α-methyloestradiol-3-methyl ether (P-5780) on cholesterol metabolism in normo-and hypercholesterolaemic rats. Oestrone and P-5780 significantly increased both the incorporation of sodium [l-14C]acetate into hepatic cholesterol and the specific activity of hepatic cholesterol in normocholesterolaemic rats. Both steroid drugs significantly lowered the plasma cholesterol/phospholipid (C/P) ratio without affecting plasma and hepatic cholesterol levels. In hypercholesterolaemic rats, P-5780 restored the inhibited [14C]-acetate incorporation into hepatic cholesterol to above the normal level, and significantly decreased both the cholesterol level and C/P ratio in plasma without any effect on the hepatic cholesterol level. In parallel with the increased incorporation of [14C]acetate into hepatic cholesterol, oestrone and P-5780 stimulated biliary excretion of [14C]bile acid in normocholesterolaemic rats but not in the hypercholesterolaemic ones. Oestrone and P-5780 seemed significantly to decrease deposition of [4-14C]-cholesterol in tissues such as liver, heart, intestine, kidney and adrenal in both normo-and hypercholesterolaemic rats, except for the increased hepatic cholesterol in hypercholesterolaemic rats. Oestrone and P-5780 did not affect faecal excretion of total 14C, neutral [14C]steroid and [14C]bile acid after oral administration of [4-14C]cholesterol to normo- and hypercholesterolaemic rats. Urinary excretion of total 14C was significantly increased in oestrone-treated animals but not in those treated with P-5780. However, urinary excretion was very low in comparison with faecal excretion. Oestrone and P-5780 seemed not to affect hepatic function, as revealed by serum alkaline phosphatase and GOT activities. However, GPT but not GOT was increased in oestrone-treated animals.