Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained unchanged. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxycholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and alpha, beta- and omega-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged. Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7 alpha-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40%. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats.
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PMID:Altered bile acid metabolism in alloxan diabetic rats. 53 73

The ability of sodium metavanadate to reverse the effects of streptozotocin-induced diabetes on hepatic cytochrome P-450 isozymes was examined in male rats. Streptozotocin caused P-450h levels to fall 95%, and P-450j and P-450b levels to rise 8- and 40-fold, respectively, after 1 week. When diabetic rats were administered metavanadate in the drinking water for 7 days, P-450h apoprotein and mRNA levels remained no different from those of untreated diabetic rats, whereas levels of P-450b and P-450j decreased toward those of control rats. Metavanadate also lowered serum triglyceride and 3-hydroxybutyrate levels without lowering serum glucose in the diabetic rats. Furthermore, P-450h mRNA levels correlated well with levels of P-450h apoprotein for all treatment groups, indicating that P-450h suppression in diabetic rats is under pretranslational control and is independent of the increased expressions of P-450j and P-450b, and of the hyperlipidemia and ketosis that occurs in diabetes. Vanadate is capable of separating the effects of diabetes on expression of individual P-450 isozymes.
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PMID:Effects of vanadate on hepatic cytochrome P-450 expression in streptozotocin-diabetic rats. 169 38

The effects of oral contraceptives (OCs) on drug therapy are related mainly to the inhibition of microsomal oxidation as well as the induction of enzymes involved in conjugation reactions. Since many drugs share these catabolic pathways, their pharmacodynamics will be affected by OCs. Notable interactions include an increased bioavailability of analgesics, tranquilizers, and tricyclic antidepressants. OCs increase the risk for hypertension, and pharmacokinetic interactions are to be expected when OCs are administered with antihypertensive drugs. Likewise, OCs affect lipid metabolism and thus modify the effects of atherogenic drugs; however, the different forms of hyperlipidemia show a heterogeneous response to OCs. Another particular concern is that the gestagen components of OCs may cause peripheral insulin resistance and may require dose adaption with antidiabetic treatments. Two common nonprescription drugs, theophylline and caffeine, show decreased clearance rates due to OCs. All share a common oxidation pathway involving cytochrome P-450 and P-448. However, cigarette smoking stimulates these enzymes, and the decreased clearance of theophylline and caffeine is usually not observed in smokers. The reports of effects of OCs and alcohol taken together are mixed, and no clinically relevant conclusions can be drawn. Most vitamin and mineral levels are influenced by OCs, but this is a concern only under conditions of deprived diet, when normal dietary adjustments are impossible. An important caveat of the many documented effects of OCs on the pharmacodynamics of other drugs is that, in most instances, these effects will be counterbalanced with kinetic changes and result in no clinical manifestation. Nevertheless, clinicians must be aware of possible adverse reactions, particularly in predisposed patients.
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PMID:Influence of oral contraceptives on drug therapy. 225 28

Advances in our knowledge of the microsomal metabolism of ethanol enable us to understand a number of complications that develop in the alcoholic. After chronic ethanol consumption, microsomal ethanol-oxidizing system (MEOS) activity increases with an associated rise in microsomal cytochrome P-450, including a form different from that induced by phenobarbital and methylcholanthrene and which has a high affinity for ethanol, as shown in reconstituted systems. The role of this MEOS in vivo and its increase after chronic ethanol consumption was most conclusively shown in alcohol dehydrogenase-negative deer mice. Microsomal induction is also associated with enhanced metabolism of other drugs, resulting in metabolic drug tolerance. Furthermore, there is increased conversion to toxic metabolites of known hepatotoxic agents (such as CCl4), which may explain the enhanced susceptibility of alcoholics to the toxicity of industrial solvents. Furthermore, the ethanol-induced form of cytochrome P-450 has a high capacity for the conversion to toxic metabolites of some commonly used drugs, such as acetaminophen, and also carcinogens, such as dimethylnitrosamine which is activated at concentrations much lower than those required for other microsomal inducers. Moreover, catabolism of retinol is accelerated through a newly discovered microsomal pathway, thereby contributing to hepatic vitamin A depletion and possibly vitamin A toxicity. There is also induction of microsomal enzymes involved in lipoprotein production, resulting in hyperlipemia. Contrasting with the chronic effects of ethanol consumption, acutely, ethanol inhibits the metabolism of other drugs through competition for an at least partially shared microsomal detoxification pathway.
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PMID:Microsomal ethanol-oxidizing system. 310 31

The hypolipidemic activity of tiadenol-disulfoxide, the major metabolite of 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) in man and in the rat was assessed in various experimental models versus the corresponding activity of tiadenol. Tiadenol-disulfoxide in the normolipidemic rats lowers total serum cholesterol and serum and liver triglycerides in an extent comparable to that of the reference compound. Likewise, it is equally effective as tiadenol in preventing Triton-induced hyperlipidemia and Nath diet induced hypercholesterolemia; in addition tiadenol-disulfoxide is slightly more effective than tiadenol in increasing HDL-cholesterol in hypercholesterolemic rats. At hypolipidemic doses the compound causes no hepatomegaly, no induction of peroxisomal catalase and palmitoyl-CoA oxidase activities, no smooth endoplasmic reticulum proliferation and no induction of microsomal cytochrome P-450 and of cytochrome P-450 dependent enzyme activities: aminopyrine (aminophenazone) N-demethylase, aniline hydroxylase, zoxazolamine hydroxylase and hexobarbital oxidase. At the suprapharmacological dose of 300 mg/kg tiadenol-disulfoxide, if compared to the reference compound, shows a generally lower order of toxicity on these hepatic parameters. Orally administered tiadenol-disulfoxide is well absorbed by the gastrointestinal tract and is eliminated in urine at 45% of the dose in unchanged form, and the remaining being: glucuron-conjugated tiadenol-disulfoxide (10%), S-oxidized metabolites (15%) and sulfoxidized carboxylic metabolites (15%). The compound is well tolerated both in mice and rats. The results of this comparative study demonstrate that: 1. tiadenol-disulfoxide is a substance with promising hypolipidemic properties; 2. tiadenol-disulfoxide is largely responsible for the hypolipidemic activity of tiadenol; 3. hepatomegaly consequent to tiadenol administration is the consequence of the response of the liver cell to the increased functional demand of the mixed function oxidase (MFO) system involved in the metabolism of the drug; 4. peroxisomal enzyme activities induction observed with both drugs at non-pharmacological doses does not play any role in their hypolipidemic action and is not associated with hepatomegaly.
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PMID:Experimental studies on pharmacology, metabolism and toxicology with tiadenol-disulfoxide. Dissociation of lipid lowering effects and the induction of peroxisomal and microsomal drug-metabolizing enzymes. 366 66

Over the years, a variety of uses has been found of organic tin compounds as fungicides, as stabilizers in plastics and for other industrial uses. The purpose of this article is to summarize and review the results so far obtained as to the analytical method for organotins in biological samples, the toxicity, metabolism, and biochemical and health effects of organotin compounds. 1) Many methods have been developed for analysis of organotin compounds by spectrophotometry, polarography, gas- or liquid-chromatography, etc. These methods, however, are mainly for analysis of organotins in standard solutions or in water, and are not suitable for organotin compounds in biological samples. Recently, we have developed several methods for analysis of various kinds of organotin compounds in biological samples. These methods are able simultaneously to separate and determine trace amounts (at nanogram order) of organotin compounds and their metabolites in the same biological samples. 2) Acute toxicity of organotin compounds which appeared on the literature are summarized. Trialkyl and triaryl compounds seem to be more toxic than the tetra-, di-, or mono-compounds of the same chain length. With an increase in the number of C atoms the toxicity of alkyl compounds decreases. Aryltin compounds are less toxic than alkyltin compounds. 3) Intestinal absorption sites for tetra-alkyltins are jejunum and duodenum, and those for trialkyltins are ileum and jejunum. A considerable amount of orally administered tetra- and trialkyltins of low molecular weights are absorbed, but only very little of the other organotin compounds seems to be absorbed from the gastrointestinal tract. Absorbed organotin compounds rapidly undergo dealkylation by the microsomal mono-oxygenase system dependent on cytochrome P-450 in the liver, brain or other organs, and the compounds and their metabolites distribute to the whole body, ultimately being excreted into urine, bile and faeces. The biological half life of organotin compounds in mammals is usually short, a half of the amount of tributyl- and triphenyl-tins deposited in the body disappearing in several days. A part of organotin compounds excreted into bile is demonstrated to have been absorbed from the intestine and to circulate in the body via enterohepatic circulation. 4) Specific effects of organotin compounds on the biological systems and health include disturbance of the structure and function of the central nervous system (interstitial edema of white matter), inhibited oxidative phosphorylation in mitochondria of cells, atrophy of the thymus and thymus dependent lymphoid tissues resulting in the dysfunction of T cells for immunity, inhibited enzyme activity, lesions in the liver and bile ducts etc., although some specificity is observed among species of animals and organotin compounds. Recently we found that a single oral administration of triphenyltin fluoride to rabbits induces transient diabetes and diabetic lipemia by inhibiting insulin secretion from morphologically normal pancreatic B-cells...
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PMID:[Recent progress in the study of analytical methods, toxicity, metabolism and health effects of organotin compounds]. 675 93

The effects of ascorbic acid (AA) or vitamin C in atherosclerosis has attracted considerable attention; however results of clinical studies are conflicting. Several studies indicate an increase in plasma triglyceride (TG) and cholesterol (CH) levels in guinea pigs (GP) that have been fed a diet containing a minimal amount of AA. Previous studies carried out in GP fed a diet devoid of AA showed a significant decrease in cytochrome P-450 level compared to GP fed high and adequate amounts; however, the level of cytochrome P-450 in the two groups were not significantly different. The enzymes that synthesize TG and CH are located in endoplasmic reticulum which is also the site for cytochrome P-450 synthesis. It is of interest to determine whether there is an association between TG and CH synthesis and cytochrome P-450 induction. Adult male Hartley GP weighing 350-400 g were fed a diet containing 2.5% (Group I), 0.1% (Group II) and 0% (Group III) AA. The food consumption and weight gain were not significantly different in different groups. After feeding the diet for four weeks, half of the animals in each group were starved. Blood was withdrawn and TG and CH were determined in the serum. TG and CH were markedly elevated in both starved and nonstarved Group III GP; however, these levels were not altered in Group 1 and Group II GP. Plasma AA showed significant differences in all three nonstarved and starved groups. Plasma alpha-lipoprotein was decreased and beta-lipoprotein was increased in Group III GP. Hepatic CH and TG were also significantly elevated in Group III GP, and Groups I and II showed no changes. TG and CH showed a negative correlation with cytochrome P-450, whereas CH and TG showed a positive correlation. We conclude that AA deficiency causes extensive hyperlipidemia, feeding high level of AA does not alter the lipid metabolism and induction ofcytochrome P-450 is inversely related to TG and CH synthesis.
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PMID:Association between hyperlipidemia and hepatic cytochrome P-450 in guinea pigs. 934 27

The treatment of hyperlipidemia in patients infected with HIV is discussed. Hyperlipidemia is common in HIV-infected patients receiving antiretroviral therapy, especially protease inhibitors and stavudine. The recommendations of the National Cholesterol Education Program (NCEP) may not entirely apply to HIV-infected patients. The pathogenesis of hyperlipidemia in these patients may make them refractory to traditional pharmacotherapy, and NCEP's emphasis on diet and exercise may be unrealistic. Other factors that may complicate treatment of hyperlipidemia include metabolism of many antiretroviral drugs by the cytochrome P-450 isoenzyme system, polypharmacy, and drug-food interactions. A patient's cardiac risk should first be assessed. Nonpharmacologic measures, such as a low-fat diet, weight reduction, and exercise, should be considered. Drug therapy is indicated for patients with familial combined hyperlipidemia that is associated with atherogenesis and for patients with triglyceride concentrations exceeding 1000 mg/dL. Drug therapy for hyperlipidemia involves niacin and statins, in addition to fibric acid derivatives and probucol. Switching among antiretroviral agents when one is found to cause hyperlipidemia should be done cautiously because of the risk for viral rebound and disease progression. NCEP guidelines recommend monitoring low-density-lipoprotein cholesterol levels four to six weeks after the start of lipid-lowering therapy and then at three months; more frequent monitoring may be necessary in HIV-infected patients. The treatment of hyperlipidemia in HIV-infected patients is complicated by their need for antiretroviral drugs, which can themselves contribute to lipid disorders.
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PMID:Treatment of hyperlipidemia in HIV-infected patients. 1129 12

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

The existence of interactions between different drugs or between drugs and the diet is becoming better and better known. Statins are medicines currently in widespread use for the treatment of hyperlipidaemias. Diet has a great influence on the prevention and/or treatment of these pathologies as the therapeutic strategy used comprises appropriate diet and, if this does not succeed, pharmacological therapy is begun in combination with dietary advice. For this reason it is necessary to be aware of the potential interactions between this kind of medication and foodstuffs in order to avoid alterations in the therapeutic benefits and even the onset of adverse side effects. All of the statins are absorbed orally, so the impact of food intake on administration is extremely important to achieve an appropriate therapeutic effect. Many of the interactions of statins lie in their metabolism through cytochrome P-450 (except for pravastatin), thus making them candidates for interaction with certain foodstuffs or compounds contained in them, such as in the case of grapefruit juice. This paper reviews the drug-nutrient interactions with special attention to the interactions specific to statins and the mechanism of these interactions is described so as to contribute to their avoidance and thus improve this form of treatment in individuals with hyperlipidaemia.
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PMID:[Interactions between foodstuffs and statins]. 1531 10


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