Differential action of progesterones on hepatic microsomal activities in the rat.

A significant reduction was found in the activity of drug-metabolizing enzymes (aminopyrine N-demethylase and coumarin 3-hydroxylase) and glucose 6-phosphatase in hepatic microsomes after the administration of reduced derivatives of progesterone (5α-pregnane-3β,-ol-20-one, 5β-pregnane-3α-ol-20-one, 5α-pregnane-3β,20β-diol and 5β-pregnane-3α,20α-diol) to rats. These steroids slightly raised inosine diphosphatase activity. On the other hand, 16α-hydroxyprogesterone and pregnenolone-16α-carbonitrile significantly increased drug metabolism and slightly elevated glucose 6-phosphatase. The contrasting action of the different progesterone derivatives was associated with changes in microsomal phospholipid synthesis. Pregnanolone and pregnanediol significantly decreased the de novo incorporation of [¹⁴C-Me]-l-methionine into microsomal phospholipids, mainly manifesting in phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine fractions; reduced the activity of S-adenosyl-l-methionine:microsomal-phosphatidylethanolamine methyl transferase; and caused a reduction of total microsomal phosphatidylcholine:phosphatidylethanolamine ratio. In contrast, 16α-hydroxy-progesterone and pregnenolone-16α-carbonitrile increased the de novo synthesis of microsomal phospholipids, methyl transferase activity and the ratio of total microsomal phosphatidylcholine: phosphatidylethanolamine. Treatment of rats with reduced progesterone derivatives diminished microsomal progesterone hydroxylation in the 16α- and 6β-position and raised progesterone Δ⁴-5α-dehydrogenase activity measured in vitro. On the other hand, 16α-hydroxyprogesterone and pregnenolone-16α-carbonitrile elevated progesterone hydroxylation. Considering these opposite effects it can be postulated that in the rat the induction of drug-metabolizing activity of the hepatic endoplasmic reticulum might be controlled by a balance displayed in the synthesis and metabolism of various progesterone derivatives.     

The effect of phenobarbital and carbon tetrachloride on fatty acid content and composition of phospholipids from the endoplasmic reticulum of rat liver

The fatty acid content and composition of hepatic microsomes of separated smooth and rough components and of isolated phosphatidylcholine and phosphatidylethanolamine fractions were studied in male albino rats treated with phenobarbital or carbon tetrachloride. Both test compounds significantly altered the fatty acid composition of the endoplasmic reticulum. The total amount was significantly raised by phenobarbital and reduced by carbon tetrachloride. Phenobarbital enhanced palmitic, stearic, arachidic, palmitoleic, linoleic, eicosenoic, eicosadienoic, eicosatrienoic, eicosapentenoic, docosatrienoic, and docosahexenoic acids. Carbon tetrachloride diminished all these, excluding palmitic and palmitoleic acids. The fatty acid content of rough microsomes was significantly increased by phenobarbital and decreased by carbon tetrachloride, while in smooth microsomes fatty acids were raised by phenobarbital but mainly unaffected by carbon tetrachloride. In microsomal phosphatidylcholine fractions, phenobarbital significantly elevated oleic, linoleic, eicosatrienoic, arachidonic, eicosapentenoic, docosapentenoic, and docosahexenoic acids, whereas all these were significantly reduced with carbon tetrachloride. In phosphatidylethanolamine fractions, phenobarbital increased palmitoleic, oleic, linoleic, and arachidonic acids; carbon tetrachloride elicited opposite effects on these acids. Phenobarbital increased and carbon tetrachloride reduced the fatty acid content in the phosphatidylcholine fraction of rough membranes. Opposite effects were seen in oleic, linoleic, arachidonic, and eicosapentenoic acids. Both test compounds brought about similar changes in the fatty acid composition of the phosphatidylethanolamine fractions of rough microsomes. In smooth microsomes, phosphatidylcholine fatty acids were significantly enhanced by phenobarbital and reduced by carbon tetrachloride. The fatty acid content of phosphatidylethanolamine was increased by phenobarbital, mainly manifesting in palmitoleic, oleic, linoleic, arachidonic, docosapentenoic, and docosahexenoic acids. Carbon tetrachloride elicited no major change in this fraction. Phenobarbital increased the production of unsaturated fatty acids, whereas carbon tetrachloride elevated the relative amount of saturated fatty acids. The saturated/unsaturated fatty acids ratio was reduced by phenobarbital and increased by carbon tetrachloride, and thus may indicate a selective difference between an inducer and hepatotoxin on fatty acid synthesis of the hepatic endoplasmic reticulum.     

Phospholipids in the liver of the pregnant rat: changes in fatty acid content and composition

Pregnancy in the rat was associated with changes in hepatic phospholipids. All changes returned to the prepregnancy levels 2 to 3 weeks postpartum. The total phospholipid content was reduced significantly, mainly representing a reduction of phosphatidylcholine, -ethanolamine, and lysophosphatidylcholine fractions. Hepatic fatty acid content was also reduced and the composition was modified since both saturated and unsaturated acyl components were decreased with more pronounced changes in unsaturated acids. Total liver saturated fatty acids with 14 to 16 carbon atoms remained unaltered; stearic acid was reduced and arachidic and lignoceric acids were elevated. Among unsaturated fatty acids, palmitoleic, oleic, eicosatrienoic, arachidonic, eicosapentaenoic, and docosapentaenoic were decreased, docosatrienoic and docosahexaenoic were raised, whereas eicosaenoic and eicosadienoic did not change. In the phosphatidylcholine and -ethanolamine fractions, unsaturated acyl components also showed significant reduction. By and large they reflected the fatty acid changes occurring in total liver with the exception of the docosahexaenoic acid which was diminished in both fractions. The overall effect of pregnancy thus indicated a modification in unsaturated fatty acid content leading to the construction of less fluid membranes which may be responsible for the reduced enzyme activity of the endoplasmic reticulum.     

Fatty acid content and composition of phospholipids bound to the hepatic endoplasmic reticulum of the rat: effect of pregnancy

Phospholipid and fatty acid content were decreased and fatty acid composition of hepatic microsomes was altered in the rat during pregnancy. These changes were reversible 2 to 3 weeks after parturition. Pregnancy-related fatty acid changes were mainly localized in phosphatidylcholine and -ethanolamine fractions. Both saturated and unsaturated fatty acids were altered, but the reduction of the unsaturated fraction was more pronounced. Saturated acyl components, such as palmitic, stearic, and lignoceric acids, and unsaturated ones, including palmitoleic, oleic, linoleic, eicosatrienoic, arachidonic, and eicosapentaenoic acids, were significantly decreased, whereas only docosahexaenoic acid was elevated. Fatty acid changes were greater in the unsaturated components in phosphatidylcholine and -ethanolamine fractions. The largest reduction was in palmitic, palmitoleic, stearic, oleic, linoleic, arachidonic, and eicosahexaenoic acid content. Pregnancy-related changes in fatty acid distribution and content, and in phospholipid fractions reflect a modified organization and disposition of the hepatic endoplasmic reticulum membranes. These membrane changes represent essentially topographical factors influencing the function and enzymatic activity of these membranes.     

The effect of phenobarbital and carbon tetrachloride on fatty acid content and composition of phospholipids from rat liver

The administration of phenobarbital or carbon tetrachloride to rats caused various changes in hepatic fatty acid content and composition. Phenobarbital elicited no effect on the total amount of fatty acids but significantly decreased myristic, pentadecanoic, and arachidonic acids and increased eicosatrienoic, eicosapentenoic, lignoceric, and docosatrienoic acid. In contrast, carbon tetrachloride enhanced significantly the total content and several components such as pentadecanoic, palmitic, palmitoleic, oleic, linoleic, arachidic, eicosenoic, eicosadienoic, eicosatrienoic, docosapentenoic, lignoceric and docosahexenoic acids. It elicited no effect on arachidonic acid. Unsaturated fatty acid moieties participating in the structure of these phosphatides were increased by phenobarbital and diminished by carbon tetrachloride. Phenobarbital caused a reduction in the ratio of saturated/unsaturated fatty acids mainly because of the decreased palmitic and increased oleic, linoleic, eicosatrienoic, arachidonic, docosapentenoic, and docosahexenoic acids. The significant variation brought about by phenobarbital and carbon tetrachloride on tissue fatty acids and in particular on fatty acid composition of phosphatidylcholine and phosphatidylethanolamine fractions reflects the opposing effects of these compounds on the liver cell. The major action of phenobarbital and carbon tetrachloride is associated with changes of the endoplasmic reticulum. Thus, their contrasting effect on fatty acid composition and metabolism may suggest that the disposition of lipid constituents plays a determinant role in the hepatic action of foreign compounds.     

Differential effects of fibrates on the acyl composition of microsomal phospholipids in rats.

1. The time-course and comparative effects of treatment with clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on the acyl composition of the main microsomal phospholipids, i.e. phosphatidylcholine and phosphatidylethanolamine, have been studied in male Sprague-Dawley rats. 2. The administration of the three fibrates caused a strong peroxisomal induction and a hypolipidaemic effect. Concerning the changes in acyl composition, CFB and BFB behaved in a similar way, with differences which could be attributed to their different potency as peroxisome inducers, whereas GFB showed a somewhat distinct profile. 3. The three drugs increased the relative content of palmitic, palmitoleic and oleic acids, whereas the levels of stearic acid and also those of long chain, highly unsaturated fatty acids docosatetraenoic, docosapentaenoic and docosahexaenoic acids were reduced. In general, these effects appeared from the first day of treatment and were highly correlated with peroxisomal proliferation. In addition, they were more evident in the phosphatidylcholine than in the phosphatidylethanolamine fraction. 4. Fibrates increased total monounsaturated fatty acids, whereas a decrease in total polyunsaturated fatty acids in the phosphatidylcholine fraction was observed in CFB- and BFB-, but not in GFB-treated rats. Clear differences appeared between CFB and BFB on the one hand, and GFB on the other when the influence of fibrate treatment on the molar percentages of linoleic, eicosatrienoic, arachidonic and mead acids was analyzed. 5. GFB increased linoleic acid content in phosphatidylethanolamine, whereas CFB and BFB decreased its level in both phospholipid fractions. In contrast, CFB and BFB enhanced eicosatrienoic and mead acids in both fractions and arachidonic acid in phosphatidylethanolamine, whereas GFB had practically no effect.     

Structural and functional changes in liver mitochondria of mice fed palmitoylethanolamide (PEA)

Repeated administration of palmitoylethanolamide (PEA) to mice, at a dose of 50 mg/kg body wt, produced a characteristic change in lipid composition of liver mitochondria. The content of the saturated fatty acids, palmitic (16:0) and stearic (18:0), decreased in the fraction of neutral lipids while the content of the unsaturated acids, palmitoleic (16:1), and oleic (18:1) and of the higher saturated acid arachidonic (20:4) increased. In contrast the amount of palmitoleic (16:1) acid decreased and palmitic (16:0) acid increased in mitochondrial phospholipids. Concomitant with these changes in the lipid composition of mitochondria changes occurred in their biochemical properties. The swelling of liver mitochondria induced by orthophosphate and by crude staphylococcal toxin is delayed in PEA-treated mice. Structural changes in mitochondrial phospholipids were confirmed with the fluorescent hydrophobic probe. The mitochondria isolated from mice pretreated with PEA had a lower fluorescence ratio than mitochondria from control animals.     

双边栝蒌种子油含量及其脂肪酸的测定

目的：测定双边栝蒌种子油的含量及其脂肪酸组成。方法：用重量法和GC-MS法测定。结果：双边栝蒌种子油含量为31.24%，脂肪酸组成以亚油酸和油酸为主，不饱和脂肪酸占脂肪酸总量的90.48%,饱和脂肪酸以棕榈酸和硬脂酸为主。结论：双边栝篓种子油属优质植物油，可作为油脂资源开发利用。     

Comparison of gamma-glutamyl transferase induction by phenobarbital in the rat, guinea pig and rabbit

Serum and hepatic γ-glutamyl transferase (GGT) activities were correlated with the microsomal markers cytochrome P-450 and aminopyrine N-demethylase after i.p. injection of phenobarbital (PB) to rats, guinea pigs and rabbits. The response to PB in the regimen employed was greatest in the rabbit and least in the guinea pig. Great disparities were observed in the microsomal protein contents following PB administration to the three species, masking the responses of the other indices when these were related to protein contents rather than to tissue weights. The increased hepatic GGT activities in PB-treated guinea pigs and rabbits were reflected in increased serum activities of this enzyme; the hepatic and serum GGT activities showed an excellent correlation with cytochrome P-450 and aminopyrine N-demethylase activities, supporting the view that the changes in GGT activity were related to enzyme induction. Although hepatic GGT activity in PB-treated rats also showed good correlation with enzyme induction indices, activity of this enzyme in rat serum was undetectable in control and PB-treated animals. Analysis of ribosome-free microsomal proteins by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis confirmed the marked increase in three bands in the PB-treated rat, but quite different changes were noted in the guinea pig and the rabbit. Our results extend knowledge about the heterogeneous response to PB shown by different animal species. The data provide further evidence that GGT is a PB-inducible enzyme, and suggest that the rabbit is the best model for elucidating the relationship between enzyme induction and GGT activity occurring in several human clinical situations.     

Effect of environmental pollutants on hepatocellular function in rats: 3-methylcholanthrene and Aroclor-1254

Environmental pollutants, Aroclor-1254 (PCB) and 3-methylcholanthrene (MC), were employed in this study to investigate some aspects of the induction of hepatic drug metabolism in rats. PCB and MC treatments increased 7-ethoxyresorufin and 7-ethoxycoumarin O-deethylase activities related to cytochrome P-448. Cytochrome P-450 reductase activity was increased by PCB while no effect was observed by MC treatment. Pretreatment with PCB resulted in approximately 50% increase in the phospholipid content of the microsomes whereas MC caused no change. Liver microsomal cholesterol content was decreased while triglycerides were increased by PCB. The ratio between saturated and unsaturated fatty acids (saturation index) decreased in the total microsomes and phospholipids with PCB treatment, whereas MC did not alter the ratio, except that the major effect of MC was observed in the acyl derivatives of microsomal phosphatidylethanolamine. It is proposed that the uniaxial rotation and mobility of hemoproteins may be restricted by an increase in the saturation index of the membrane, while a decreased index may facilitate contact with reductases for electron transfer by enhanced membrane fluidity. The decreased saturation index after treatment with MC may play a role in carcinogenicity by triggering induction of free radicals.     

Effect of amphetamine on the hepatic endoplasmic reticulum of the pregnant rat

Search for the elucidation of the mode of action of amphetamines has revealed that this drug brought about changes in the activity of some enzymes bound to the hepatic endoplasmic reticulum of the pregnant and non-pregnant rat. Amphetamine administration caused loss of appetite and changes in enzyme activity due to starvation, however, its effects were assessed applying pair-feeding conditions.Drug-metabolizing activity was increased by amphetamine as measured by coumarin 3-hydroxylase and aminopyrine N-demethylase in both pregnant and non-pregnant animals; aniline hydroxylase was elevated only in pregnant rats. These changes were associated with the enhanced synthesis of microsomal phospholipids as indicated by the increased activity of [¹⁴C-Me]S-adenosyl-l-methionine : microsomal phospholipid methyl transferase, de novo synthesis and levels of microsomal phospholipids. These effects were mainly manifest in phosphatidylethanolamine and phosphatidylcholine fractions. Glucose-6-phosphatase activity remained unaltered by amphetamine. Pregnancy alone brought about a reduction of all these microsomal parameters.The rise of hepatic drug metabolism following the administration of amphetamine indicated a compensatory mechanism by means of stimulating enzyme induction processes.     

Synergistic inhibition of DNA synthesis in Ehrlich ascites tumour cells by a combination of unsaturated fatty acids and hyperthermia

Wide attention has been given to hyperthermia as a new measure for cancer treatment. Clinical trials of hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic we examine if fatty acids exert a synergistic effect on Ehrlich ascites tumour cells when combined with hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic acid and linoleic acid (unsaturated fatty acids) at 37 degrees C, the DNA synthesis of cells was significantly inhibited. Palmitic and stearic acids, which are saturated fatty acids, did not suppress DNA synthesis. Hyperthermic treatment without the presence of fatty acids at 42 degrees C for 1 h decreased DNA synthesis to 62% of the control level of 37 degrees C. The combination of an unsaturated fatty acid and hyperthermia synergistically suppressed DNA synthesis. When the cells were incubated in serum-free medium containing 0.1% albumin, unsaturated fatty acids were more effective in inhibiting DNA synthesis. However, saturated fatty acids had little or no effect on DNA synthesis in control or hyperthermia-treated cells. These results indicate that unsaturated fatty acids are useful for enhancing the inhibitory effect of hyperthermia on DNA synthesis, which may increase the in vitro antitumour effects of hyperthermia.     

Toxicity of fatty acids on murine and human melanoma cell lines.

High concentrations of certain fatty acids can cause cell death via apoptosis or necrosis. The aim of this study was to investigate the toxicity of saturated and unsaturated fatty acids on melanoma cell lines, which was evaluated by either loss of membrane integrity and/or DNA fragmentation using flow cytometric analysis. Evidence is presented that saturated and unsaturated fatty acids exert toxic effects on melanoma cells through loss of membrane integrity and/or DNA fragmentation. Arachidonic and linoleic acids were the most effective in decreasing the number of viable S91 murine melanoma cells, causing loss of membrane integrity and DNA fragmentation at 100 microM concentration already after 24 h in culture. In B16F10 murine melanoma cells, palmitic acid was the most toxic, inducing cell death by both apoptosis and necrosis. The human melanoma cell lines were more resistant to the toxic effect of fatty acids. In SK-Mel 23 cells, indications of cytotoxicity were detected only after 48 h treatment with arachidonic, linoleic, palmitic and palmitoleic acids at 200 microM concentration. Linoleic acid was the most toxic for this cell line. In SK-Mel 28 human cells, only palmitic acid caused a significant decrease of the number of viable cells, inducing DNA fragmentation after 24 and 48 h treatments at 200 microM concentration.     

Investigations on changes in ¹³C/¹²C ratios of endogenous urinary steroids after pregnenolone administration

For the detection of possible misuse of naturally occurring anabolic androgenic steroids like testosterone (T), anti-doping laboratories use a combination of two techniques. One is molecular steroid profiling to evaluate urinary steroid concentrations and normal diagnostic ratios. The other is isotope ratio mass spectrometry (IRMS), in which the 13C/12C ratios of target analytes like T are compared to the 13C/12C ratios of endogenous reference compounds (ERCs). The 13C/12C of the most commonly used ERC, pregnanediol (5β-pregnane-3α,20α-diol, PD), can be influenced by administration of pregnenolone (3β-hydroxy-pregn-5-en-20-one, PREG). Therefore PREG administration bears the potential to circumvent IRMS testing for doping control samples. In order to investigate the influence of PREG on PD and on other urinary excreted steroids, administration studies with oral and transdermal application of PREG were carried out. The influence of PREG administration on concentrations and 13C/12C ratios of all investigated target analytes was negligible. Only PD and 5β-pregnan-3α-ol-20-one (3aP) showed significant depletion in both their glucuronidated and sulfated steroids. The results suggest that appropriate alternative ERCs are: 11β-hydroxy-androsterone/etiocholanolone, 5β-pregnane-3α,17,20α-triol, pregn-5-ene-3β,17,20α-triol and cholesterol. Due to its properties to disguise the misuse of anabolic steroids by influencing the 13C/12C ratio of PD, PREG should be considered to be added to the World Anti-Doping Agency (WADA) list of prohibited substances as a masking agent.     

Study on the effect of eicosapentaenoic acid on phospholipids composition in membrane microdomains of tight junctions of epithelial cells by liquid chromatography/electrospray mass spectrometry

Tight junctions of epithelial cells determine epithelial membrane integrity and play an important role in selective paracellular permeability to ions and macromolecules. In this work, we investigated the effect of one of n-3 series polyunsaturated fatty acids, eicosapentaenoic acid (EPA) on the phospholipid composition of membrane microdomains of tight junctions. After treated by EPA, membrane microdomains of tight junctions were isolated by discontinuous sucrose density gradient ultracentrifugation, and raft phospholipids were extracted. The PE, PI, PS, PC and SM were separated and determined by high-performance liquid chromatography/quadrupole-linear ion trap mass spectrometry (HPLC Qtrap-MS), and were further identified by HPLC–MS/MS. It was found that EPA altered the fatty acyl substitution of phospholipids that constituted membrane microdomains of tight junctions by enriching the unsaturated fatty acyl chains of the phospholipids. It provides a new visual angle to explaining the intracellular mechanism involved in n-3 polyunsaturated fatty acids (PUFAs) modulation of intestinal tight junction barrier.     

The effect of coenzyme Q10 against the attack of phospholipase to myocardial membrane

This study was designed to clarify the biochemical and electrophysiological influences of phospholipase (PLase) A2 and PLase C on canine myocardial membrane and to investigate the effect of coenzyme Q10 (CoQ10) against the action of these enzymes. Nine different species of free fatty acids (FFA), i.e., lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, arachidonic and docosahexaenoic acids were detected in myocardial membrane preparations by a high performance liquid chromatography. Incubation of the membrane with PLase A2 increased all of the unsaturated FFA, but not the saturated FFA. Incubation with PLase C increased all of the detected FFA. While PLase A2 and PLase C induced deleterious effects on myocardial membrane potentials, such as decreasing in the resting potential and in the magnitude of action potential, and shortening of the action potential duration. Premedication with CoQ10 significantly prevented all of these biochemical and electrophysiological changes induced by the action of PLases, suggesting that CoQ10 exerts a protective effect on myocardial membrane against the attack of PLases.     

Analysis of sterols and fatty acids in natural and cultured Cordyceps by one-step derivatization followed with gas chromatography–mass spectrometry

Ten free fatty acids namely lauric acid, myristic acid, pentadecanoic acid, palmitoleic acid, palmitic acid, linoleic acid, oleic acid, stearic acid, docosanoic acid and lignoceric acid and four free sterols including ergosterol, cholesterol, campesterol and β-sitosterol in natural (wild) Cordyceps sinensis, Cordyceps liangshanensis and Cordyceps gunnii, as well as cultured C. sinensis and Cordyceps militaris were first determined using pressurized liquid extraction (PLE), trimethylsilyl (TMS) derivatization and GC–MS analysis. The conditions such as the amount of reagent, temperature and time for TMS derivatization of analytes were optimized. Under the optimum conditions, all calibration curves showed good linearity within the tested ranges. The intra- and inter-day variations for 14 investigated compounds were less than 3.4% and 5.2%, respectively. The results showed that palmitic acid, linoleic acid, oleic acid, stearic acid and ergosterol are main components in natural and cultured Cordyceps which could be discriminated by hierarchical clustering analysis based on the contents of 14 investigated compounds or the 4 fatty acids, where the contents of palmitic acid and oleic acid in natural Cordyceps are significantly higher than those in the cultured ones.     

Different effects of fibrates on the microsomal fatty acid chain elongation and the acyl composition of phospholipids in guinea-pigs.

1. The effects in vitro and in vivo of three fibric acid derivatives, clofibrate (CFB), bezafibrate (BFB) and gemfibrozil (GFB) on some enzyme activities related to fatty acid biosynthesis, namely palmitoyl-CoA synthetase and hydrolases (microsomal and cytosolic), NADH and NADPH cytochrome c reductases and acyl-CoA elongases were investigated in guinea-pigs. 2. The three fibrates inhibited acyl-CoA elongation in vitro, irrespective of the substrate of elongation used (saturated, monounsaturated, polyunsaturated) and with an order of potency GFB > BFB > CFB. In the case of GFB, inhibition occurred at concentrations that can be reached in vivo. 3. Microsomal palmitoyl-CoA hydrolase and synthetase were also inhibited in vitro (GFB > or = BFB > CFB), whereas NADH cytochrome c reductase activity was increased by GFB. Nevertheless, the magnitude of changes were lower than those observed in elongation activities. 4. Treatment with fibrates did not produce peroxisomal proliferation in guinea-pigs, as measured by peroxisomal beta-oxidation activity and liver weight/body weight ratio. Nevertheless, fibrates provoked a reduction in plasma cholesterol and triglycerides, at least in GFB- and BFB-treated animals. 5. Fatty acid elongation was significantly modified by GFB treatment in vivo. The remaining enzyme activities studied were only slightly changed by fibrate treatment. 6. Treatment with BFB and to a lesser extent with CFB, increased the relative proportion of MUFA (palmitoleic and oleic acids) in microsomal phospholipids, whereas PUFA (mainly linoleic acid) decreased. GFB behaved differently, increasing palmitic and linoleic acids and decreasing stearic and oleic acids. The latter changes are attributable to an inhibition of elongation activity by GFB. 7. The changes observed after fibrate treatment in both rats and guinea-pigs, as they are not directly related to peroxisome proliferation, could be more reliably extrapolated to man than those observed only in rats.     

Effect of acute nitrogen dioxide exposure on the composition of fatty acids in lung and liver phospholipids

In order to examine the effects of NO₂ on the fatty acid content of the lung and liver phospholipids, the phospholipid fractions of rats exposed to 20 ppm NO₂ for 20 and 40 h were extracted and analyzed using gas chromatography. Among the fatty acid species in the lung, the relative amount of palmitic acid, palmitoleic acid and linoleic acid increased significantly, whereas myristic acid, stearic acid and oleic acid decreased significantly after exposure to NO₂. These changes in the composition of fatty acids are discussed in comparison with the results of acute, subacute and chronic exposure to NO₂ reported by other workers. In the case of the fatty acid species in the liver, a significant increase for stearic acid and arachidonic acid and a decrease in oleic acid were observed.     

Species variation in the ouabain sensitivity of cardiac Na+/K+-ATPase. A possible role for membrane lipids

The role of membrane lipid composition on the modulation of ouabain sensitivity of cardiac Na+/K+-ATPase has been studied in vitro using several animal species. The animals can be grouped as ouabain-sensitive and ouabain-insensitive species. Ouabain-sensitive species (I50; 0.5-2.2 microM) include sheep, marmoset, pig and the guinea pig, whilst rat and mouse form the ouabain-insensitive group (I50; 100-105 microM). Although no species variation in the distribution of major phospholipid classes was observed, significant differences were apparent in the proportions of certain saturated and unsaturated phospholipid fatty acids. Thus, there was a marked increase in the relative proportion of docosahexaenoic (22:6, omega-3) acid in the Na+/K+-ATPase preparations from the rat and mouse compared to ouabain-sensitive species. Despite these differences, all animals had similar proportions of total saturated (sigma SAT) and total unsaturated (sigma Unsat) fatty acids. On the other hand, a good correlation between the unsaturation index of membrane lipids and I50 value for ouabain was observed. It is proposed that acyl chain characteristics (unsaturation and/or chain length) rather than the head group of the phospholipid molecule play a major role in the modulation of Na+/K+-ATPase to inhibition by ouabain.