scholarly journals Triacylglycerol metabolism in the phenobarbital-treated rat

1981 ◽  
Vol 196 (1) ◽  
pp. 337-346 ◽  
Author(s):  
David M. Goldberg ◽  
M. Waheed Roomi ◽  
Alexander Yu ◽  
Daniel A. K. Roncari
Keyword(s):  
Enzyme Induction ◽  
Diacylglycerol Acyltransferase ◽  
Female Rats ◽  
Male Rats ◽  
Microsomal Enzyme ◽  
Triacylglycerol Metabolism ◽  
Triacylglycerol Content ◽  
Hepatic Triacylglycerol ◽  
Microsomal Enzyme Induction

1. Various aspects of triacylglycerol metabolism were compared in rats given phenobarbital at a dose of 100mg/kg body wt. per day by intraperitoneal injection; controls were injected with an equal volume of 0.15m-NaCl by the same route. Animals were killed after 5 days of treatment. 2. Rats injected with phenobarbital demonstrated increased liver weight, and increased microsomal protein per g of liver. Other evidence of microsomal enzyme induction was provided by increased activity of aminopyrine N-demethylase and cytochrome P-450 content. Increased hepatic activity of γ-glutamyltransferase (EC 2.3.2.2) occurred in male rats, but not in females, and was not accompanied by any detectable change in the activity of this enzyme in serum. 3. Phenobarbital treatment increased the hepatic content of triacylglycerol after 5 days in starved male and female rats, as well as in non-starved male rats; non-starved females were not tested in this regard. At 5 days after withdrawal of the drug, there was no difference in hepatic triacylglycerol content or in hepatic functions of microsomal enzyme induction between the treated and control rats. 4. After 5 days, phenobarbital increased the synthesis in vitro of glycerolipids in cell-free liver fractions fortified with optimal concentrations of substrates and co-substrates when results were expressed per whole liver. The drug caused a significant increment in the activity of hepatic diacylglycerol acyltransferase (EC 2.3.1.20), but did not affect the activity per liver of phosphatidate phosphohydrolase (EC 3.1.3.4) in cytosolic or washed microsomal fractions. A remarkable sex-dependent difference was observed for this latter enzyme. In female rats, the activity of the microsomal enzyme per liver was 10-fold greater than that of the cytosolic enzyme, whereas in males, the activities of phosphohydrolases per liver from both subcellular fractions were similar. 5. The phenobarbital-mediated increase in hepatic triacylglycerol content could not be explained by a decrease in the hepatic triacylglycerol secretion rate as measured by the Triton WR1339 technique. Since the hepatic triacylglycerol showed significant correlation with microsomal enzyme induction functions, with hepatic glycerolipid synthesis in vitro and with diacylglycerol acyltransferase activity, it is likely to be due to enhanced triacylglycerol synthesis consequent on hepatic microsomal enzyme induction. 6. In contrast with rabbits and guinea pigs, rats injected with phenobarbital showed a decrease in serum triacylglycerol concentration in the starved state; this decrease persisted for up to 5 days after drug administration stopped, and did not occur in non-starved animals. It seems to be independent of the microsomal enzyme-inducing properties of the drug, and may be due to the action of phenobarbital at an extrahepatic site.

scholarly journals Effects of phenobarbital upon triacylglycerol metabolism in the rabbit

1980 ◽  
Vol 192 (1) ◽  
pp. 165-175 ◽  
Author(s):  
D M Goldberg ◽  
M W Roomi ◽  
A Yu ◽  
D A K Roncari
Keyword(s):  
Enzyme Induction ◽  
Microsomal Enzyme ◽  
Gamma Glutamyltransferase ◽  
Triacylglycerol Metabolism ◽  
Triacylglycerol Synthesis ◽  
Triacylglycerol Content ◽  
Phosphatidate Phosphohydrolase ◽  
Hepatic Triacylglycerol ◽  
Microsomal Enzyme Induction

1. The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male rabbits (2kg body wt.) injected intra-peritoneally with 50 mg of phenobarbital per kg for 10 days. 2. Occurrence of enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity and cytochrome P-450 content, as well as a doubling of microsomal protein per g of liver and a 54% increase in liver weight. Parallel increments in hepatic gamma-glutamyltransferase (EC 2.3.2.2) activity occurred; these were more pronounced in the whole homogenate than in the microsomes, which only accounted for 12.5% of the total enzyme activity in the controls and 17.0% in the animals given phenobarbital. Increased activity of gamma-glutamyltransferase activity was also observed in the blood serum of the test animals. 3. The rabbits given phenobarbital manifested increased hepatic triacylglycerol content and the triacylglycerol concentration of blood serum was also elevated. These changes were accompanied by a significantly enhanced ability of cell-free fractions of liver from the test animals (postmitochondrial supernatant and microsomal fractions) to synthesize glycerolipids in vitro from sn-[14C] glycerol 3-phosphate and fatty acids, when expressed per whole liver. Relative to the protein content of the fraction, glycerolipid synthesis in vitro was significantly decreased in the microsomes, presumably consequent upon the dramatic increase in their total protein content, whereas no change occurred in the postmitochondrial supernatant, possibly due to the protective effect of cytosolic factors present in this fraction and known to enhance glycerolipid synthesis. 4. Microsomal phosphatidate phosphohydrolase accounted for 85% of the total liver activity of this enzyme and its specific activity was 20-fold higher than that of the cytosolic phosphatidate phosphohydrolase (EC 3.1.3.4), when each was measured under optimal conditions. A significant increase in the activity of both enzymes per whole liver occurred in the rabbits given phenobarbital. A closer correlation between hepatic triacylglycerol content and and microsomal phosphatidate phosphohydrolase, as well as the above observation, suggest that this, rather than the cytosolic enzyme, may be rate-limiting for triacylglycerol synthesis in rabbit liver. 5. Significant correlations were observed between the various factors of hepatic microsomal-enzyme induction (aminopyrine N-demethylase and gamma-glutamyltransferase activity as well as cytochrome P-450 content) and hepatic triacylglycerol content, suggesting that that microsomal enzyme induction may promote hepatic triacylglycerol synthesis and consequently hypertriglyceridaemia in the rabbit.

Effects of phenobarbital upon triacylglycerol metabolism in the guinea pig

1981 ◽  
Vol 59 (1) ◽  
pp. 48-53 ◽  
Author(s):  
David M. Goldberg ◽  
Alexander Yu ◽  
M. Waheed Roomi ◽  
Daniel A. K. Roncari
Keyword(s):  
Guinea Pig ◽  
Enzyme Induction ◽  
Guinea Pigs ◽  
Microsomal Enzyme ◽  
Triacylglycerol Metabolism ◽  
Triacylglycerol Synthesis ◽  
Hepatic Microsomal Enzyme ◽  
Triacylglycerol Content ◽  
Hepatic Triacylglycerol ◽  
Microsomal Enzyme Induction

The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male guinea pigs injected intraperitoneally with 50 mg phenobarbital∙kg−1 for 7 days. Enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity, cytochrome P450 content, and hepatic γ-glutamyltransferase activity. Increased activity of γ-glutamyltransferase was also observed in the blood serum of treated animals. The phenobarbital-treated guinea pigs manifested increased hepatic triacylglycerol content and serum triacylglycerol concentration, accompanied by enhanced ability of cell-free fractions of liver to synthesize glycerolipids in vitro from sn-[14C]glycerol 3-phosphate and fatty acids. Microsomal phosphatidate phosphohydrolase accounted for 97% of the total liver activity of this enzyme, and its specific activity was 50-fold higher than that of the cytosolic enzyme when each was measured under optimal conditions. Activity of the cytosolic phosphohydrolase per liver doubled and that of the microsomal phosphohydrolase increased by 40% in the phenobarbital-treated guinea pigs. The microsomal, but not the cytosolic enzyme, showed a significant correlation with hepatic triacylglycerol content. Significant correlation was observed between the various parameters of hepatic microsomal enzyme induction and hepatic triacylglycerol content, suggesting that enzyme induction may promote triacylglycerol synthesis and consequent hypertriglyceridaemia in the guinea pig.

Enzyme induction and hepatic glycerolipid synthesis in rats treated with 3-methlcholanthrene

1981 ◽  
Vol 59 (9) ◽  
pp. 793-798 ◽  
Author(s):  
D. M. Goldberg ◽  
M. W. Roomi ◽  
A. Yu ◽  
D. A. K. Roncari
Keyword(s):  
Enzyme Induction ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Male Rats ◽  
Microsomal Enzyme ◽  
Aryl Hydrocarbon ◽  
Triacylglycerol Content ◽  
Glycerolipid Synthesis ◽  
Hepatic Triacylglycerol

Fasting male rats fed 3-methylcholanthrene in a daily dose of 40 mg∙kg body weight−1 gave evidence of hepatic microsomal enzyme induction after 3 days through significantly increased hepatic aryl hydrocarbon hydroxylase activity, cytochrome P448 content, and characteristic changes in microsomal proteins analysed by sodium dodecyl sulfate – polyacrylamide gel electrophoresis. Concomitantly, activities of aminopyrine N-demethylase and microsomal γ-glutamyltransferase, which are increased in phenobarbital-treated rats, significantly declined. In contrast to phenobarbital, which has been previously shown to increase hepatic triacylglycerol content and in vitro glycerolipid synthesis, 3-methylcholanthrene did not affect hepatic triacylglycerol content, but did inhibit glycerolipid synthesis by cell-free preparations of rat liver and significantly reduced serum triacylgiycerol concentration. Thus, the two prototypical drugs inducing characteristically different changes in microsomal enzyme and hemoprotein response also seem to differ in their effect upon another important microsomal function, hepatic glycerolipid synthesis.

Actions of prednisolone acetate, pregnenolone-16α-carbonitrile, and triamcinolone upon drug resistance and metabolism: a comparative study

1977 ◽  
Vol 55 (3) ◽  
pp. 363-366 ◽  
Author(s):  
P. Kourounakis ◽  
H. Selye
Keyword(s):  
Plasma Concentrations ◽  
The Body ◽  
Female Rats ◽  
Prednisolone Acetate ◽  
Microsomal Enzyme ◽  
Enzyme Inducer ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Microsomal Enzyme Induction

In female rats, pretreatment with prednisolone acetate diminished the duration of zoxazolamine-induced paralysis as well as its plasma concentrations and increased significantly the in vitro metabolism of zoxazolamine and ethylmorphine. These actions of prednisolone were compared with those of equimolar amounts of pregnenolone-16α-carbonitrile (PCN) (a known microsomal enzyme inducer) and of triamcinolone (an agent that reduces the sensitivity of the body to drugs although not via microsomal enzyme induction). Prednisolone proved to be a strong drug-metabolizing enzyme inducer but it was less potent than PCN.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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