PubMed Health⌕ Search

Biomedical subjects

M Laitinen

Publications and source records attributed to M Laitinen.

At least 73 records · Page 4Linked to original sources
PubMed1982

Dietary cholesterol-induced changes of xenobiotic metabolism in liver. I. Influence of xenobiotic administration on hepatic membrane structure.

We have studied the effects of dietary lipids on the structure and function of hepatic endoplasmic reticulum by feeding rats either with a 2% cholesterol or cholesterol-free diet. Rats were further administered either phenobarbitone, carbon tetrachloride, or both in combination to reveal possible differences in the response of the microsomal membranes to xenobiotics. Cholesterol feeding increased the membrane cholesterol contents and also carbon tetrachloride increased microsomal cholesterol contents in those rats fed a cholesterol-free diet. Also the microsomal phospholipid contents were higher in those rats fed 2% cholesterol diet than in those fed cholesterol-free diet and in the 2% cholesterol group also phenobarbitone increased the phospholipid contents. In addition, there were changes in the phospholipid-fatty acid proportions between rats fed 2% cholesterol and cholesterol-free diets. When 1,8-ANS was used as a fluorescence probe, phenobarbitone increased the fluorescence in both the dietary groups, while carbon tetrachloride decreased it; less change was present using PNA as a substrate. When Scatchard plots were constructed phenobarbitone changed the turning point more in the cholesterol-free group than in the 2% cholesterol group, while reversed orders of changes were found with carbon tetrachloride. The results demonstrated that dietary cholesterol has profound effects on the structure of microsomal membranes far beyond changes in their cholesterol content. The membrane fluidity also changes owing to alterations in the phospholipid contents and in their fatty acid composition.

1-Naphthylamine↗
PubMed1981

Tricaine (MS-222) induced modification on the metabolism of foreign compounds in the liver and duodenal mucosa of the splake (Salvelinus fontinalis X Salvelinus namaycush).

The splake, a popular game fish, is a crossbreed which must be reared in nurseries. The fish are marked under anesthesia for later study. We analyze the effect of a common anesthetic, tricaine (MS-222), on the metabolism of foreign compounds in the liver and duodenum of the splake. In the liver and to some extent in the duodenum, aryl hydrocarbon hydroxylase and epoxide hydrase activities were reduced during treatments. The ethoxycoumarin O-deethylase activities were not affected in either the liver or duodenum. Tricaine significantly decreased the hepatic UDP-glucuronosyltransferase activity. The decrease was greater when the aglycone used was p-nitrophenol than with methylumbelliferone. A similar effect was also found after trypsin treatment of the microsomes. No significant decrease in the UDP-glucuronosyltransferase activity was detected in the duodenal mucosa. This was the case when both p-nitrophenol and methylumbelliferone were used as aglycones.

Aminobenzoates↗
PubMed1980

Hepatic drug metabolism during ethanol ingestion in riboflavin deficient rats.

Riboflavin deficiency was induced by feeding rats a riboflavin-deficient diet for 1 month. In order to find out if there are any combined effects of ethanol and riboflavin deficiency on drug metabolism, a group of riboflavin-deficient rats were also given ethanol in their drinking water. At the end of the feeding period, hepatic drug-metabolizing enzyme activities were determined. The hepatic phospholipid and protein contents were the same in rats receiving a standard diet and in those on a riboflavin-deficient diet. However, ethanol ingestion in both groups enhanced significantly the phospholipid content. Ethanol ingestion also markedly enhanced the hepatic cytochrome P-450 concentration in rats fed either a standard or riboflavin-deficient diet. Ethoxycoumarin O-deethylase activity was significantly lower in riboflavin-deficient rat livers than in those of the controls. In both groups ethanol ingestion nearly doubled the activities. Aryl hydrocarbon hydroxylase activity was also significantly decreased during riboflavin deficiency. However, ethanol administration did not change the activities of this enzyme. UDP glucuronosyltransferase activity was slightly lower in riboflavin-deficient rat livers than in those fed a standard diet. No significant decrease was found in the epoxide hydrase activity in the riboflavin-deficient rats. However, the riboflavin-deficient rats had enhanced activity after the ethanol ingestion.

Animals↗
PubMed1980

On the effects of nutrition on the metabolism of foreign compounds in the liver of reindeer (Rangifer tarandus tarandus L).

The effects of seasonal feeding on the structure and function of the hepatic microsomes of the reindeer were studied. In native microsomes the protein content did not vary depending on seasonal feeding, but there was a slight modification of the lipid moiety. The sensitivity of microsomes to membrane treatments changed from season to season. Seasonal feeding did not affect the hepatic cytochrome c reductase activity. However, the poor winter food depressed UDPglucuronosyltransferase activity to one third of that after summer feeding. The UDPglucuronosyltransferase activity was lower in both native and treated microsomes. No differences were found in serum activities of aspartate or alanine aminotransferase although there were changes in the structure and function of hepatocytes. The poor winter feeding of the reindeer decreases their capacity to glucuronate foreign compounds and this is mediated by structural modification on the hepatic endoplasmic reticulum.

Alanine Transaminase↗
PubMed1980

Effect of administration route of 3-methylcholanthrene on the inducibility of intestinal drug-metabolizing enzymes.

The inducibility of the mucosal drug-metabolizing enzymes of rat small intestine was studied by administering 3-methylcholanthrene either intragastrically or intraperitoneally. The aryl hydrocarbon hydroxylase activity was 4.1 times higher after intragastric than after intraperitoneal administration of methylcholanthrene. The ethoxycoumarin-O-diethylase activity was 11 times and UDP-glucuronosyltransferase (with p-nitrophenol as substrate) activity was 3 times higher after intragastric administration than after intraperitoneal administration. The epoxide hydratase activity was, on the other hand, 38% lower after intragastric administration of 3-methylcholanthrene than after intraperitoneal administration. The results suggest that compounds entering the body intragastrically, e.e. in the diet, might have profound enzyme-specific effects on the intestinal metabolic rates of drugs.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1978

The copper induced modification of duodenal biotransformation reactions in rats during fat deficiency.

The effect of ingested copper on the composition of duodenal postmitochondrial supernatnat fraction (PMS), the aryl hydrocarbon hydroxylase (AHH) and UDPglucuronosyltransferase (GT) activities was analyzed in rats given normal or fat free diets. There were only minor changes in the composition of PMS or in the activities of the measured enzymes when rats received a normal diet. During fat deficiency the phospholipid-protein ratio and the GT activity were markedly increased following 10 mM copper concentration in the drinking water. It is concluded that during fat deficiency copper modifies the structure of the microsomes, as analyzed in the PMS, and that this is reflected in the membrane bound GT activity.

Animals↗
PubMed1978

Dietary cholesterol-induced enhancement of hepatic biotransformation rate in male rats.

Male rats were fed a cholesterol-free diet for 5 weeks, followed by a 2% cholesterol diet for 4 weeks. Another group of rats was continuously fed a cholesterol-free diet. A third group was fed standard pelllets during the whole experiment. Hepatic microsomal protein and cholesterol contents and drug-metabolizing enzyme activities were measured. The cholesterol-rich diet increased microsomal protein content and this increase disappeared after trypsin digestion of microsomal membranes. Microsomal cholesterol content was enhanced three-fold by cholesterol feeding. Cytochrome P-450 concentration, NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities showed only minor changes following cholesterol feeding. The p-nitroanisole O-demethylase and ethoxycoumarin deethylase activities were doubled by cholesterol in comparison to cholesterol-free diet. Trypsin digestion activated the UDP-glucuronosyltransferase enzyme eight- to ten-fold on a protein basis. Trypsin treatment increased the cholesterol activation of UDP-glucuronosyltransferase when compared to the activity in native microsomes. The data suggest that dietary cholesterol regulates the cholesterol content of microsomal membranes. The activities of drug-metabolizing enzymes are also altered, possibly due to the compositional changes of the membranes.

Animals↗
PubMed1978

Regulation of hepatic drug metabolism by elaidic and linoleic acids in rats.

Elaidic and linoleic acids were administered at doses of 40 and 200 mg/kg i.p. every second day for 4 weeks to rats fed a fat-free diet. The fatty acids had only a slight effect on the weight gain of the animals. The amount of microsomal protein was slightly decreased with the higher dose of linoleic acid. The higher dose level of both fatty acids decreased the microsomal phospholipid content. The relative amounts of microsomal phospholipid fatty acids were also altered due to fatty acid administration. The activity of microsomal NADPH cytochrome c reductase and microsomal cytochrome P-450 contents were decreased by the higher dose of linoleic acid. The hepatic aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities decreased in fatty acid-treated rats. The UDP-glucuronosyltransferase activity was also lowered after the fatty acid administration. The results suggest that fatty acid-induced changes in the activities of drug-metabolizing enzymes may be due to the microenvironmental changes of membrane-bound enzymes.

Animals↗
PubMed1976

Hepatic and duodenal drug metabolism in the rat during fat deficiency.

1. The effect of dietary fat deficiency on the composition of hepatic microsomes and postmitochondrial supernatant fraction of duodenal mucosa and on the activities of drug-metabolizing enzymes was studied in the rat. 2. There were only little changes in the measured protein, cholesterol and phospholipid fractions in the liver microsomes. In the postmitochondrial supernatant fraction of the duodenal mucosa, however, protein content was increased during fat deficiency. 3. In the fatty acid composition of hepatic microsomal phospholipids marked differences took place during fat deficiency. The amount of palmitoleic and eicosatrienoic acids increased from undetectable level to the amount of 6.9 and 9.5%. Also the amount of oleic acid was almost doubled and the content of linoleic and arachidonic acid was markedly decreased. 4. Fat deficiency was found to affect the drug metabolism both in the liver and small intestine. Only minor changes took place in the measured hydroxylative enzyme activities but the activity of UDPglucuronosyltransferase was highly depressed during fat deficiency both in the liver microsomes and in the postmitochondrial supernatant of duodenal mucosa. The changes in the UDPglucuronosyltransferase activity are concluded to be mediated via changes in the lipoidal environment of the enzyme in the membranes.

Animals↗
PubMed1975

Dietary fats and properties of endoplasmic reticulum: I. Dietary lipid induced changes in composition of microsomal membranes in liver and gastroduodenal mucosa of rat.

Rats were fed for four weeks with different lipid diets to determine the effects on the endoplasmic reticulum membranes of the liver and on the postmitochondrial supernatant fraction of the gastroduodenal mucosa. The diets contained cholesterol, cacao butter, olive oil, and these in combination. The results showed that dietary lipids were able to modify the composition of the hepatic endoplasmic reticulum and, to a lesser extent, that of postmitochondrial fraction of gastroduodenal mucosa. Cacao butter in the diet decreased the relative proportion of protein in hepatic microsomes. Cholesterol and olive oil were able to increase the cholesterol content of microsomes. The trypsin digestion of membranes revealed that cholesterol increased the solubility of microsomal protein and decreased the trypsin sensitive protein-lipid binding. The neutral fat diets increased the binding of proteins to the membrane, and cholesterol had no effect when it was given in combination. The low power photomicrographs revealed vacuolization of the cytoplasm of the hepatocytes when rats were fed on lipid rich diets. Also fatty degeneration was present. Cholesterol in combination with olive oil, however, did normalize the structure of the hepatocytes to a marked extent.

Animals↗
PubMed1975

Dietary fats and properties of endoplasmic reticulum: II. Dietary lipid induced changes in activities of drug metabolizing enzymes in liver and duodenum of rat.

Rats were fed cholesterol, cacao butter, or olive oil diets to determine the effect of dietary lipids on the rate of drug biotransformation in the liver and duodenum. The cholesterol rich diet maintained the hepatic aryl hydrocarbon hydroxylase activity at the same level as did the standard diet. Rats fed olive oil and cacao butter diets showed lower hepatic aryl hydrocarbon hydrorylase activity. The p-nitroanisole O-demethylase activity was doubled in hepatic microsomes of rats fed the high cholesterol diet when compared to rats fed the standard diet. The hepatic uridine diphosphate glucuronosyltransferase activity showed different patterns depending on the in vitro treatment of the microsomal membranes. If the enzyme activity was assayed from the native, untreated microsomes, an increase in the measurable uridine diphosphate glucuronosyl transferase activity was found in rats having cholesterol rich diet. After the in vitro activation of membrane-bound uridine diphosphate glucuronosyltransferase by trypsin, the increase in measurable activity was 10 fold in the group fed the standard diet, 6 fold in group fed cholesterol, 4 fold in group fed cacao butter, and 3 fold in group fed olive oil. Trypsin digestion of microsomes increased the measurable uridine diphosphate glucuronosyltransferase activity less in rats fed diets rich in neutral fats than those fed the standard diet. In the duodenal mucosa, lipid diets decreased the activities of drug hydroxylation and glucuronidation.

Animals↗
PubMed1975

Enhancement of hepatic drug biotransformation rate by polychlorinated biphenyls in rats fed cholesterol-rich diet.

A combined effect of cholesterol and polychlorinated biphenyls (PCBs) on the microsomal drug hydroxylation and glucuronidation in the liver of the rat was studied. PCBs, Clophen A-50 and A-60, having an average chlorination degree of 50 and 60% affect the structure of microsomal membranes. It was found that Clophen A-60 increased the binding of trypsin- and digitonin-sensitive proteins to the membranes. Also it was found that PCBs enhanced the phsopholipid content of microsomes. PCBs increased the activity of hepatic NADPH cytochrome c reductase about 1.5-fold. Aryl hydrocarbon hydroxylase activity doubled with Clophen A-50 and quadrupled with Clophen A-60. Hepatic UDPglucuronosyltransferase activity was doubled with both PCBs. The enhancement in hepatic aryl hydrocarbon hydroxylase and in UDPglucuronosyltransferase was found to be lower in the presence of high cholesterol level in the diet when compared to earlier results. This is supposed to be due to the membraneous effects of cholesterol.

Animals↗
PubMed1975

Inducibility of mucosal drug-metabolizing enzymes of rats fed on a cholesterol-rich diet by polychlorinated biphenyl, 3-methylcholanthrene and phenobarbitone.

The results show that a cholesterol-rich diet changes the composition of mucosal membranes. A high cholesterol diet increases mucosal cholesterol and phospholipid contents. Cholesterol enhanced mucosal NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities as well as mucosal UDP glucuronosyltransferase activity. When phenobarbitone or Clophen A 50 or 60 were administered intraperitoneally to cholesterol-fed rats, the hydroxylation and glucuronidation activities decreased to a lower level. 3-Methylcholanthrene was, however, able to maintain or increase mucosal hydroxylative enzymes and UDP glucuronosyltransferase. These results indicate that the drug-metabolizing enzymes of the intestinal mucosa behave very differently from those in the liver. Diet apparently has a regulatory effect on the induction of drug-metabolizing enzymes because only a very potent inducer, 3-methylcholanthrene, was able to maintain and even induce mucosal drug-metabolizing enzymes in rats fed on a high cholesterol diet, possibly through changes in the microenvironment of enzymes caused by cholesterol.

Animals↗