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Results for “Triparanol”

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At least 19 recordsLinked to original sources

PubMed1975

Absorption of morphine, butylscopolamine, mecamylamine and phenobarbitone from the small intestine of the triparanol-treated rat in situ.

The absorption of three basic drugs (morphine, butylscopolamine and mecamylamine) and an acidic drug (phenobarbitone) from the rat small intestine in situ was investigated by using a single perfusion technique. The effect of intestinal damage on absorption was studied by treating rats with triparanol 25-50 mg/kg every 24 h for three weeks. Treatment with triparanol decreased the cholesterol concentration in the intestinal wall. The absorption of morphine and mecamylamine was increased by treatment with triparanol, whereas the absorption of butylscopolamine was decreased and that of phenobarbitone remained unaltered. Treatment with triparanol decreased the concentration of mecamylamine in the intestinal wall, but the concentrations of other drugs were unchanged. When comparing the present in situ and previous in vitro results the decreased absorption of butylscopolamine after triparanol in situ was opposite to the finding in vitro. The increased absorption of morphine and unaltered absorption of phenobarbitone were in accordance with the finding in vitro. In situ the absorption of mecamylamine was increased, although in vitro it was unchanged. The structural damage, differences in composition of the intestinal wall and intestinal blood flow are supposed to be the reasons for changes in absorption.

Animals↗

PubMed1976

Functional and biochemical evidence of damage to enterocytes induced by triparanol: role of lysosomes and the effect of gluten-free diet.

1. Functional and biochemical studies were performed on the small intestine of control rats, and the results were compared with similar studies on animals given triparanol at a dosage of 0.114 mmol/kg daily for 10 days. The animals given triparanol were fed with either standard rat food or a gluten-free diet. 2. By using a recirculating-perfusion technique in vivo, it was shown that absorption of galactose from an 8 mmol/l solution was impaired in the ileum but not in the jejunum of the triparanol-treated rats. 3. Assays of marker enzymes for the principal subcellular organelles were performed on isolated jejunal and ileal enterocytes. In the ileum there was a striking decrease in lysosomal enzyme activities and a smaller but significant decrease of lactate dehydrogenase, catalase and malate dehydrogenase activities. In the jejunum there was no significant change in the activities of these enzymes. 4. Measurements of lysosomal integrity indicated that ileal lysosomal fragility was markedly increased and that jejunal lysosomes were affected to a much smaller extent. 5. These effects of triparanol could not be ameliorated by feeding with a gluten-free diet.

Acetylglucosaminidase↗

PubMed1981

Lipid composition and (Na+ + K+)-ATPase activity in rat lens during triparanol-induced cataract formation.

The development of triparanol cataracts in rats is accompanied by the loss of lens (Na+ + K+)-ATPase activity and by alteration in the lens content and composition of phospholipids, sterols and phospholipid acyl groups. The lipid changes occur along the same time course as the loss of (NA+ + K+)-ATPase activity. Triparanol feeding produces a decrease in lens phospholipid content. The percentage contents of phosphatidylcholine and phosphatidyl-serine decrease while the content of sphingomyelin substantially increases. The amounts of oleic acid in lens phospholipids decrease while stearic and palmitic acids increase; however, these changes are relatively small. Sterol content is also decreased while the percentage content of desmosterol increases markedly. Feeding of the cataractogenic agents galactose and diazacholesterol also alters the lens lipid compositions and (Na+ + K+)-ATPase activity. A loss of phosphatidylserine is the only change in lipid properties which always accompanies a loss of the enzyme activity. The possible relationships between the lens content of phosphatidylserine, (Na+ + K+)-ATPase activity and the mechanism of triparanol-induced cataract formation are discussed.

Animals↗

PubMed1984

Fatty acid metabolism in Paramecium. Oleic acid metabolism and inhibition of polyunsaturated fatty acid synthesis by triparanol.

Paramecium requires oleic acid for growth and can grow in media containing no other fatty acids. In the present study, we have shown that this ciliate utilized oleate mainly as a carbon and energy source, even though this fatty acid was the only substrate available for synthesis of polyunsaturated fatty acids. Culture growth was inhibited by the addition of the drug triparanol. Triparanol decreased the formation of polyunsaturated fatty acids from oleate by preventing desaturation to form the dienoic acid, linoleate. Triparanol inhibition resulted in an altered phospholipid fatty acyl composition, an increased fragility and an altered behavioral response of the cells to a depolarizing stimulation solution. Therefore, although most of the dietary oleate was not used by the cells for polyunsaturated fatty acid synthesis, the desaturation of oleic acid was critical for normal culture growth, cell integrity and swimming behavior, all of which are expected to be dependent on normal membrane lipid composition.

Animals↗

PubMedDate not supplied

Effect of triparanol on cholesterol absorption in rhesus monkeys.

The drug, triparanol, a known inhibitor of cholesterol biosynthesis, was found to interfere with absorption of cholesterol in rhesus monkeys. The percent luminal cholesterol absorbed decreased by 13 and 21%, respectively, in the high- and low-responding monkeys when the drug was fed along with the low-cholesterol, low-plant sterol diet. When the diet contained large amounts of plant sterols, feeding of the drug also reduced the percent cholesterol absorption by the same order of magnitude. The results showed that triparanol decreased the absorption of endogenous cholesterol in rhesus monkeys. The effect of the drug on cholesterol absorption was independent of that of plant sterols. The mechanism(s) of the observed inhibitory effect of triparanol on cholesterol absorption is not clearly understood.

Animals↗

PubMed1984

Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by tamoxifen and other triparanol analogues.

The effects of the triparanol analogues chlorotrianisene, clomiphene, tamoxifen, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (MDL 10393), MDL 8917v, nafoxidine, 2-[p-(6-methoxy-2-phenylinden-3-yl)phenoxy]triethylamine (U-11555A), 2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]triethylamine (U-10520A), and nitromifene, as well as triparanol itself, were studied in the P388 murine leukemia cell line and in a doxorubicin-resistant subline (P388/ADR). At noninhibitory concentrations, all the analogues increased the sensitivity of P388/ADR cells to doxorubicin but did not have such an effect on the doxorubicin-sensitive cells. Diethylstilbestrol, deacetylated cyclofenil (F6060), hexestrol, and 17 beta-estradiol did not have such an activity. The effects of tamoxifen on doxorubicin sensitivity of P388/ADR cells could not be reversed by 17 beta-estradiol. Estrogen receptors could not be demonstrated in either cell line. It is therefore suggested that the reversal of the doxorubicin-acquired resistance by the triparanol analogues is unrelated to their estrogenic or antiestrogenic activities. The possible clinical implications of these findings are discussed.

Animals↗

PubMed1980

Selective biliary secretion of basal and glucagon-inhibited neutral sterol after triparanol administration.

Biliary cholesterol secretion was studied in dogs with chronic bile fistulas, using glucagon, an inhibitor of biliary cholesterol secretion, and triparanol, an inhibitor of cholesterol synthesis. Glucagon inhibited neutral sterol secretion before and after triparanol administration. Triparanol caused a significant accumulation in bile of the cholesterol precursor desmosterol which comprised a significant portion of the neutral sterol in bile but not in blood. Glucagon inhibited both biliary desmosterol and cholesterol secretions to a similar degree. These findings suggest that biliary cholesterol is derived from newly synthesized hepatic sterol as well as from equilibrated sources. Furthermore, glucagon suppressed biliary secretion of both equilibrated as well as newly synthesized neutral sterol, suggesting that glucagon inhibits the movement of neutral sterol to or through the canalicular membrane.

Animals↗

PubMed1999

Calcium increase in mouse skeletal muscles by triparanol: a drug to induce myotonic dystrophy-like clinical manifestations.

Triparanol (Trp) is known to cause clinical features similar to those seen in myotonic dystrophy, including myotonia, cataract and baldness. To explore the pathophysiological mechanism of myotonic dystrophy, we examined the effect of Trp on intracellular calcium in cultured skeletal myoblasts and myotubes as well as cardiac myocytes by using a fluorescent indicator. Trp preferentially induced increase of intracellular calcium in myotubes of skeletal muscles. Since the increase of calcium was inhibited by thapsigargin pretreatment but not by extracellular calcium elimination, it appears that triparanol might act mostly on intracellular calcium stores. Trp also inhibited the increase of calcium in myotubes induced by acetylcholine. Trp might cause myotonia possibly through the increase of intracellular calcium from intracellular stores.

Acetylcholine↗

PubMed1989

Inhibition of cholesterol synthesis and cell growth by 24(R,S),25-iminolanosterol and triparanol in cultured rat hepatoma cells.

24(R,S),25-Iminolanosterol (IL) and triparanol added to cultures of rat hepatoma cells, H4-II-C3 (H4), interrupt the conversion of lanosterol to cholesterol and, depending on their concentrations, cause the accumulation in the cells of intermediates in the lanosterol to cholesterol conversion. At 45 microM, both substances cause the accumulation of 5 alpha-cholesta-8(9),24-dien-3 beta-ol (zymosterol), and at the low concentration of 4.5 microM, they cause the accumulation of cholesta-5.24-dien-3 beta-ol (desmosterol). The effect of intermediate concentrations of 9 or 22.5 microM of either substance is to cause the accumulation in the cells of three sterols: cholesta-5,7,24-trien-3 beta-ol, zymosterol, and desmosterol. The synthesis of these intermediary sterols, not found normally in H4 cells, is particularly pronounced in cultures kept in lipid-depleted media that contain the inhibitors and proceeds by the use of endogenous substrates at the expense of cholesterol. The synthesis of cholesterol from [14C]acetate or [2-14C]mevalonate is completely blocked by either inhibitor even at 4.5 microM. IL or triparanol inhibits the growth of H4 cells. Cells seeded into either full growth or lipid-depleted medium containing 22.5 microM IL will not grow unless the media are supplemented with low density lipoproteins (60 micrograms/ml). Supplementation of the media with 4.6 mM mevalonate does not counteract the inhibitory effect of IL on cell growth.

Animals↗

PubMed1977

Effects of zuclomiphene in combination with triparanol and ay-9944 on developing rat CNS morphology and biochemistry.

Developing rats were injected intraperitoneally twice weekly with a combination of three hypocholesterolemic agents: Zuclomiphene (formerly called trans-clomiphene; dosage, 30 mg/kg body weight), Triparanol (30 mg/kg body weight) and AY-9944 (3 mg/kg body weight). Treatment was initiated at 4 days of age. Biochemical and electron microscopic examination was conducted on animals sacrificed at 20 days of age. Cytoplasmic inclusion bodies were not seen in the CNS. Isolated edematous changes were seen in myelinated axons. Analysis of the sterol content of the brain and spinal cords of drug-treated animals indicated the presence of abnormal concentrations of five sterols, desmosterol, 5alpha-cholesta-7,24-dien-3beta-ol, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). Zymosterol and 5alpha-cholesta 7,24-dien-3beta-ol were minor constituents (5--7% and 1--1.5% of total sterol, respectively). The 7-dehydrosterols represented approximately one-half (44--52%) of the total CNS sterol.

Animals↗

PubMed1975

Myeloid bodies formation in triparanol treated cultured cells.

Cultured cells (chicken embryo liver cells and rat embryo fibroblasts) were treated with triparanol (MER-29) for various lengths of time. Both types of cells have developed numerous membranous whorls-myeloid bodies in the cytoplasm. Various stages in myeloid bodies development are described. Acid phosphatase activity was cytochemically demonstrated within the myeloid bodies, indicating their lysosmal nature. This activity appeared only at a late stage of the myeloid bodies formation.

Acid Phosphatase↗

PubMed1982

Fungal transformations of triparanol.

Fungal transformations of triparanol, a hypercholesterolemic drug, were studied in Lagenidium giganteum and Lagenidium callinectes. The products were identified by combined gas chromatography-mass spectrometry. Two metabolites were observed from each organism; only one of the metabolites was found in both organisms.

Biotransformation↗

PubMed1979

Effects of diazacholesterol, triparanol, and beta-sitosterol on egg cholesterol deposition in coturnix quail.

Studies were undertaken to determine the effect of inhibitors of cholesterol synthesis on deposition of cholesterol in eggs of Japanese quail. Results indicate that this bird responds similarly to the laying hen, making it a useful screening device for these types of compounds. Administration of either triparanol or 20,25 diazacholesterol resulted in a decreased cholesterol content of the yolk. Concomitant with this decrease was an increase in desmosterol deposition. Beta sitosterol (2%) fed either alone or with lecithin (2%) did not result in a decrease in egg yolk cholesterol. No beta-sitosterol was found in the egg yolk. Diazacholesterol fed either with sitosterol, or sitosterol plus lecithin, was not effective in reducing the total sterol content of egg.

Administration, Oral↗

PubMed1963