Liver Phospholipid Content Research Articles

Effect of long term fluoride exposure on lipid composition in rat liver

Chronic fluorosis can severely damage many systems of human body, but its pathogenesis is unclear. Normal composition and structure of cellular membrane lipids are a basic factor to maintain cell function. In this investigation, cellular membrane lipids of the liver were analysed after a long term fluoride treatment for rats and the results are discussed in order to give an explanation for the pathogenesis of this disease. Wistar rats were supplied with drinking water containing either 30 or 100 ppm fluoride (NaF) for seven months. Contents of phospholipid and neutral lipid in rat liver were analyzed by high-performance liquid chromatography, and fatty acid composition from individual phospholipids was measured by gas chromatography. Results showed that the total liver phospholipid content decreased in the rats treated with high dose of fluoride due to a lower content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Among the fatty acid compositions of PE and PC in the livers of fluoride poisoned animals, the proportion of polyunsaturated fatty acids (20:4 and 22:6) decreased, whereas saturated fatty acids (16:0 and 18:0) increased. No changes could be detected in the amounts of liver cholesterol and dolichol. Total ubiquinone contents in rat liver were reduced by 11% in the group treated with 30 ppm fluoride and by 42% in the group treated with 100 ppm fluoride. In the subclasses of ubiquinone, both ubiquinone-9 and ubiquinoine-10 amounts decreased after fluoride treatment. These modifications of membrane lipids might be induced by oxidative stress, which might be an important factor in the pathogenesis of chronic fluorosis.

Modulation of fetal rat brain and liver phospholipid content by intraamniotic ethyl docosahexaenoate administration.

In an attempt to elucidate the role of docosahexaenoic acid (DHA; 22:6n-3) in the developing brain, a method was devised whereby rapid enrichment of fetal brain and liver lipid with DHA was achieved. Fetal rats at 17 days of gestation were injected intraamniotically with ethyl docosahexaenoate (EtDHA). Control fetuses were administered ethyl oleate (EtOle). Brain lipid DHA content increased by almost 21% (p = 0.02) 3 days after EtDHA administration as compared with EtOle-injected fetuses, whereas liver lipid DHA content increased by almost 60% (p = 0.0002). At this time brain phosphatidylinositol content doubled, whereas phosphatidylserine (PS) content increased by > 50% (p = 0.03). Increases in liver PS (+25.8%; p = 0.015) and sphingomyelin (+43.6%; p = 0.01) content were observed. A redistribution of total brain phospholipid (PL) DHA was observed following EtDHA administration, resulting in a 56.4% increase in PS-DHA abundance (p < 0.05) and an 8.8% decrease in phosphatidylethanolamine-DHA abundance (p = 0.05). These results suggest modulation of fetal brain and liver PL and provide a method for enrichment of DHA content in discrete PLs during intrauterine life.

Effects of addition of arginine, cystine, and glycine to the bovine milk-simulated amino acid mixture on the level of plasma and liver cholesterol in rats.

The effects of the addition of varying levels of arginine (Arg), cystine (Cys), and glycine (Gly) to the bovine milk-simulated amino acid mixture on the levels of plasma and liver cholesterol were investigated in rats. The diets containing a high amount of Cys lowered significantly the level of plasma cholesterol as the amount of Cys in diets increased. The serum high density lipoprotein (HDL)-cholesterol level and fecal excretion of acidic steroids were higher in rats fed the Cys diets than in those fed the Arg and Gly diets. No differences, however, was observed in the content of liver cholesterol. Liver triglyceride contents elevated significantly on feeding the Arg and Cys diets. Furthermore, liver phospholipid contents elevated significantly on feeding the Arg diet but lowered on feeding the Cys diet. Therefore, these results indicated that the feeding of a high amount of Cys lowers the plasma cholesterol levels as the result of the enhanced conversion of cholesterol to bile acids.

Chloroquine treatment does not cause phospholipid storage by depleting rat liver lysosomes of acid phospholipase a

Chronic treatment of rats with chloroquine causes phospholipid storage in the lysosomes of liver and other tissues. This could be due to chloroquine-induced depletion of liver lysosomal phospholipase A. Alternatively, it could be caused by chloroquine inhibition of intralysosomal phospholipid catabolism. We treated rats with chloroquine in a dosage schedule sufficient to cause a 35% increase in liver phospholipid content. Acid phospholipase A activity was increased in liver homogenates and in lysosomal preparations obtained from chloroquine-treated animals. Thus, while fibroblasts respond to chloroquine treatment by cellular depletion of certain acid hydrolases as shown by others, the levels of acid phospholipase A increase in liver. Our results provide additional new support for the hypothesis that inhibition of lysosomal phospholipase A activity is the major mechanism of chloroquine-induced phospholipidosis.

Liver Lipid Levels in White Leghorn Hens Fed Diets That Contained Wheat Contaminated by Deoxynivalenol (Vomitoxin)

Three genotypes of White Leghorn hens were fed diets containing either clean wheat (<.02 ppm deoxynivalenol in diet) or deoxynivalenol (vomitoxin) contaminated wheat (.35 or .70 ppm deoxynivalenol in diet) for 86 or 135 days. Lipid analyses indicated that the percent total lipid and the triglyceride content of livers from birds receiving the vomitoxin contaminated diets were significantly higher than for birds receiving the clean diet. However, the livers of birds receiving the .35 ppm diet had the highest percent total lipid and triglycerides. Livers from control birds contained 11.5% total lipid with 420 mg triglyceride per liver; livers from the .35 ppm birds had 16.7% total lipid, 785 mg triglyceride; livers from the .70 ppm birds had 13.4% total lipid, 548 mg triglyceride. Liver phospholipid content did not appear to be affected by the deoxynivalenol content of the diet. Both genotype and level of vomitoxin in the diet significantly affected liver cholesterol levels.

Biochemical changes resulting from the intraperitoneal administration of mercuric chloride and methylmercuric chloride to mice

I.p. administration of mercuric chloride (HgCl 2) and methylmercuric chloride (MeHgCl) at 1 mg/kg body wt./day for 10 consecutive days markedly influenced the phospholipid, DNA, RNA and protein of various tissues of mice. HgCl 2 led to a significant increase (42%) in the liver phospholipid content but to a similar decrease in kidney phospholipid. MeHgCl reduced the phospholipid content of the brain and kidney. Kidney DNA decreased following administration of both HgCl 2 and MeHgCl. MeHgCl resulted in the depleted rates of 32P uptake in the DNA fraction of all tissues studied. Both compounds increased liver and testis RNA and reduced the protein content and the 32P uptake from the protein fraction in all tissues studied.

Studies on drug-induced lipidosis: subcellular localization of phospholipid and cholesterol in the liver of rats treated with chloroquine or 4,4'-bis (diethylaminoethoxy)alpha, beta-diethyldiphenylethane.

Administration of chloroquine or 4,4'-bis(diethylaminoethoxy)alpha, beta-diethyldiphenylethane (DH) to rats in oral doses of 100 mg/kg for 7 days causes phospholipid and cholesteryl ester accumulation in liver. To further characterize this drug-induced lipidosis, we have isolated and characterized the lipids of subcellular fractions from control rats and rats treated with chloroquine, DH, and Triton WR-1339. The phospholipid content of liver is increased 1.5-fold by chloroquine or DH treatment but is unaffected by Triton WR-1339. Acid phosphatase is increased by treatment with these three agents. Chloroquine and DH cause a shift of acid phosphatase from the light mitochondrial fraction (L) to the heavy mitochondrial fraction (M). Multilamellar bodies, an ultrastructural hallmark of chloroquine and DH-induced lipidosis, were isolated in a highly-purified form from the M fraction of chloroquine- or DH-treated rats. They are highly enriched in acid phosphatase indicating their lysosomal origin. In addition, they contain large amounts of phospholipid, cholesterol, and cholesteryl ester and are the sole site of bis(monoacylglycero)phosphate and the enzyme which catalyzes its synthesis from phosphatidylglycerol. Analysis of the phospholipid content of the respective control and drug-treated liver fractions shows that the entire excess phospholipid content of chloroquine- or DH-treated liver can be accounted for by the drug-induced multilamellar bodies. Triton WR-1339-induced lysosomes, which were isolated for comparison, also contain bis(monoacyglycero)phosphate and bis(monoacyglycero)phosphate synthetase. However, they differ from the drug-induced lysosomes in that their sphingomyelin content is much higher and their total phospholipid and phosphatidylinositol content much lower. The multilamellar bodies are the principal intracellular site of accumulation of chloroquine and DH, respectively. Increased delivery of phospholipid to lysosomes and decreased lysosomal catabolism of phospholipid are the factors which are thought to cause this experimental lipidosis. High levels of phosphatidylinositol in the multilamellar body may be in part responsible for the increased content of bis(monoacyglycero)phosphate since it has been identified as an acyl donor in bis(monoacylglycero)phosphate synthesis.

Deleterious effects of subacute carbon disulphide exposure on mouse liver

Female mice, fed ad lib., were exposed to 1.5 mg of carbon disulphide per liter of air for 4 hr a day, 5 days a week, for approximately 3.5 weeks. During the first week of the experiment the liver changes were similar to those found after acute carbon disulphide intoxication, i.e microsomal cytochropie P-450 content was lowered, the activities of NADPH cytochrome c-reductase and 7-ethoxycoumarin deethylase were decreased and the measurable UDP-glucuronosyltransferase activity was increased. The copper and phospholipid contents of the liver were also increased somewhat. Later on the activities of the microsomal enzymes were either partially or totally restored in spite of continuing exposure. The liver phospholipid content was also restored. The activity of UDP-glucuronosyltransferase was decreased significantly below the control level. The diene conjugation of liver phospholipids was increased, and this finding indicates that the exposure was able to damage the membrane lipids of the liver continuously. It is suggested that the partial or total restoration of the enzyme activities resulted either from their decreased sensitivity to the toxic metabolites of carbon disulphide or from their stimulated synthesis. The increased diene conjugation of the liver phospholipids indicates that the lipid environment of membrane bound enzymes changes during subacute exposure to carbon disulphide.

The effect of ethyl α-p. Chlorophenoxyisobutyrate on ethanol-induced hepatic steatosis in the rat

Several mechanisms have been invoked to explain the increased liver triglyceride content induced in the rat by alcohol. It has been stated that alcohol promotes hepatic synthesis of triglyceride and increases hepatic α-glycerophosphate levels. Alcohol has also been shown to promote preferential incorporation of FFA into triglycerides rather than into phospholipids. Following an acute intoxicating dose of alcohol, excessive mobilization of FFA from adipose tissue has been documented by some observers. As it has been demonstrated that the drug CPIB causes an increase in liver phospholipid content and interferes with release of fatty acid and glycerol from adipose tissue, the effect of this drug was observed in the rat on serum and liver lipid changes induced by alcohol. A single oral dose of ethanol, 6 Gm./Kg., resulted in lower serum FFA levels, lower liver triglyceride levels, and higher liver phospholipid levels in rats pretreated for 2 weeks with CPIB as 0.25 per cent by weight of diet than in a matched group of animals receiving a normal diet. The liver triglyceride content was higher and the liver phospholipid content was lower in CPIB-treated rats given alcohol than in CPIB-treated rats fed glucose. Although modification by CPIB of the lipid changes induced by alcohol suggests that the drug may interfere with adipose tissue lipolysis, it is also possible that the effect of alcohol is modified following a direct effect of CPIB on hepatocellular function. No difference in adipose tissue lipoprotein lipase content was found in CPIB-treated and untreated animals 16 hours after glucose ingestion.

Phospholipid content in Novikoff hepatoma, regenerating liver and in liver of fed and fasted normal rats

The phospholipid content of normal liver, Novikoff hepatoma and regenerating liver was investigated. The effect of 6 days fasting on the phospholipid content of normal rat liver was also studied. 1. 1. The phospholipid content of Novikoff hepatoma was decreased to 44 and 73 per cent of that of the normal liver when expressed per wet weight or per mg nitrogen respectively. The phospholipid content in an average cell of the Novikoff hepatoma was only 32 per cent of that of an average normal liver cell. 2. 2. The phospholipid content per unit was increased in the regenerating liver at 1 day after partial hepatectomy. At 3, 8, and 22 days after partial hepatectomy the phospholipid content per unit was the same in the regenerating liver as in the sham-operated controls. 3. 3. The restoration of total liver phospholipid content was more rapid at 1 day after partial hepatectomy than the rate of restoration of liver weight, total liver nitrogen, total liver cell number, and liver/body weight ratio. However, at 3 days the total liver phospholipid restoration rate paralleled the restoration rate of the examined liver constituents and liver/body weight ratio. 4. 4. The 6 days fasting resulted in a decrease of 50 per cent in the phospholipid content (per average cell) of rat liver. 5. 5. The significance of the decrease of phospholipid content in the hepatoma and the changes in the regenerating liver were discussed.

THE PHOSPHOLIPID CONTENT OF LIVER, SKELETAL MUSCLE AND WHOLE BLOOD AS AFFECTED BY THYROXINE INJECTIONS

ArticleTHE PHOSPHOLIPID CONTENT OF LIVER, SKELETAL MUSCLE AND WHOLE BLOOD AS AFFECTED BY THYROXINE INJECTIONSL. H. SchmidtL. H. SchmidtFrom The Christ Hospital Institute of Medical Research, Cincinnati, Ohio and the Department of Biochemistry, University of CincinnatiPublished Online:31 Jan 1935https://doi.org/10.1152/ajplegacy.1935.111.1.138MoreSectionsPDF (863 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 111Issue 1January 1935Pages 138-144 Copyright & PermissionsCopyright © 1935 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1935.111.1.138History Received 12 September 1934 Published online 31 January 1935 Published in print 31 January 1935 Metrics