Effect of hydrophobic surfactant (Pluronic L-81) on lymphatic lipid transport in the rat

1980 ◽  
Vol 239 (5) ◽  
pp. G348-G353 ◽  
Author(s):  
P. Tso ◽  
J. A. Balint ◽  
J. B. Rodgers

The effect of chronic feeding (3-4 wk) of the hydrophobic surfactant, Pluronic L-81, on the lymphatic transport of triglyceride and cholesterol was studied in rats with thoracic duct fistula. A lipid emulsion containing [3H]triolein (13.3 mM), [14C]cholesterol (2.6 mM), phosphatidylcholine (2.9 mM), sodium taurocholate (19 mM), with 0.17 mg/ml (experimental) or without Pluronic L-81 (L-81) added (control) was infused at the rate of 3 ml/h. Lymph triglyceride and cholesterol outputs were greatly impaired in the experimental rats compared to the control rats. The phospholipid output compared to the control was also reduced but to a lesser extent in the experimental rats. Comparable recovery of radioactive 3H-labeled lipid and [14C]cholesterol from the intestinal lumen of control and experimental rats showed that digestion and absorption were not impaired in the experimental rats. The distribution of mucosal 3H radioactivity in various lipid fractions showed no impairment in reesterification. The greatly depressed lymphatic lipid transport was associated with marked accumulation of absorbed lipid in enterocytes, suggesting that Pluronic L-81 interferes with lipoprotein assembly and/or exit of lipoproteins from the mucosal cells. The animals fed chronically for 4-6 wk regained their ability to transport lipid 24 h after termination of L-81 feeding. The effect of this agent, therefore, is readily reversible.

1957 ◽  
Vol 188 (2) ◽  
pp. 342-346 ◽  
Author(s):  
George V. Vahouny ◽  
Isa Fawal ◽  
C. R. Treadwell

The lipid fractions of thoracic duct lymph in unanesthetized rats were determined following intragastric administration of saline-albumin emulsions containing various combinations of cholesterol, taurocholate and oleic acid. Sodium taurocholate or oleic acid alone produced significant increases in the total lipid, neutral fat and phospholipid fractions, but had no effect on the level of free and ester cholesterol. Administration of cholesterol alone was without effect on any of the fractions. The combination of taurocholate and oleic acid gave the same levels of lipid fractions as when they were administered singly except that there was an elevation of ester cholesterol indicating increased absorption of endogenous cholesterol. Cholesterol plus taurocholate or oleic acid produced the same increases in the fractions as the salt or acid alone except that with both combinations there were highly significant increases in the total and ester cholesterol fractions. Administration of the three factors together gave further increases in all fractions except neutral fat and free cholesterol. The amount of free cholesterol was constant throughout all groups, even in those in which there was absorption of exogenous cholesterol. The percentage of ester cholesterol in the total cholesterol of lymph ranged from 66 to 81 with the higher percentages in the groups where cholesterol absorption occurred. The esterification of the ‘extra’ cholesterol in lymph due to cholesterol absorption ranged from 86 to 92%. It is suggested that essentially all of the cholesterol transferred from the intestinal lumen to the lacteals is esterified.


2016 ◽  
Vol 311 (4) ◽  
pp. G648-G654 ◽  
Author(s):  
Alison B. Kohan ◽  
Qing Yang ◽  
Min Xu ◽  
Dana Lee ◽  
Patrick Tso

It is not well understood how monosodium glutamate (MSG) affects gastrointestinal physiology, especially regarding the absorption and the subsequent transport of dietary lipids into lymph. Thus far, there is little information about how the ingestion of MSG affects the lipid lipolysis, uptake, intracellular esterification, and formation and secretion of chylomicrons. Using lymph fistula rats treated with the infusion of a 2% MSG solution before a continuous infusion of triglyceride, we show that MSG causes a significant decrease in both triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished lymphatic transport of triglyceride and cholesterol was not caused by an accumulation of these labeled lipids in the intestinal lumen or in the intestinal mucosa. Rather, it is a result of increased portal transport in the animals fed acutely the lipid plus 2% MSG in the lipid emulsion. This is a first demonstration of MSG on intestinal lymphatic transport of lipids.


1990 ◽  
Vol 259 (3) ◽  
pp. G386-G393 ◽  
Author(s):  
S. E. Bergstedt ◽  
H. Hayashi ◽  
D. Kritchevsky ◽  
P. Tso

Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri[9,10 (n)-3H]oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl [1,3-14C]tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.(ABSTRACT TRUNCATED AT 250 WORDS)


1982 ◽  
Vol 242 (2) ◽  
pp. G147-G155 ◽  
Author(s):  
F. Hartmann ◽  
R. Owen ◽  
D. M. Bissell

Intestinal mucosal cells from the rat have been isolated by a new technique involving intravascular perfusion of an intestinal segment with collagenase. Detached cells were flushed from the intestinal lumen with a second perfusion circuit containing an oxygenated buffered solution with 1% bovine serum. Sequential collection of cells at intervals during the period of perfusion revealed that villus-tip cells are recovered first (after 15 min of collagenase perfusion), followed by midvillus (after 25 min) and lower villus cells (after 35 min). The isolated cells were judged intact and viable by the criteria of trypan blue dye exclusion, ultrastructural appearance, and metabolic activity. They were characterized as villus-tip, midvillus, and lower villus-crypt cells by their alkaline phosphatase and sucrase activity, glycoprotein formation, and [3H]thymidine incorporation. Microsomal monooxygenase activity was four to five times greater in villus-tip than in lower villus cells, whereas heme oxygenase exhibited a reverse gradient. The isolated cells synthesized heme and bilirubin under cell culture conditions.


1998 ◽  
Vol 274 (5) ◽  
pp. G797-G801 ◽  
Author(s):  
Manabu Nishikawa ◽  
Kenta Takeda ◽  
Eisuke F. Sato ◽  
Tetso Kuroki ◽  
Masayasu Inoue

Nitric oxide (NO) inhibits the respiration of mitochondria and enteric bacteria, particularly under low O2concentration, and induces apoptosis of various types of cells. To gain insight into the molecular role of NO in the intestine, we examined its effects on the respiration, Ca2+status, and expression of Bcl-2 in cultured intestinal epithelial cells (IEC-6). NO reversibly inhibited the respiration of IEC-6 cells, especially under physiologically low O2concentration. Although NO elevated cytosolic Ca2+as determined by the fura 2 method, the cells were fairly resistant to NO. Kinetic analysis revealed that prolonged exposure to NO elevated the levels of Bcl-2 and suppressed the NO-induced changes in Ca2+status of the cells. Because Bcl-2 possesses antiapoptotic function, toxic NO effects might appear minimally in enterocytes enriched with Bcl-2. Thus NO might effectively exhibit its antibacterial action in anaerobic intestinal lumen without inducing apoptosis of Bcl-2-enriched mucosal cells.


2015 ◽  
Vol 308 (7) ◽  
pp. G634-G642 ◽  
Author(s):  
Linda S. Zhang ◽  
Min Xu ◽  
Qing Yang ◽  
Robert O. Ryan ◽  
Philip Howles ◽  
...  

Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial plasma TG, an independent predictor for atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but mechanisms focus on increased lipolysis or clearance of remnant particles. Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut. This study examines how apoA-V deficiency affects the steady-state absorption and lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake and lymphatic transport of lipids during a continuous infusion of an emulsion containing [3H]triolein and [14C]cholesterol. ApoA-V KO mice showed a twofold increase in3H ( P < 0.001) and a threefold increase in14C ( P < 0.001) transport into the lymph compared with WT. The increased lymphatic transport was accompanied by a twofold reduction ( P < 0.05) in mucosal3H, suggesting that apoA-V KO mice more rapidly secreted [3H]TG out of the mucosa into the lymph. ApoA-V KO mice also produced chylomicrons more rapidly than WT ( P < 0.05), as measured by the transit time of [14C]oleic acid from the intestinal lumen to lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of chylomicron particles over time, as measured by lymphatic apoB output. The data suggest that apoA-V suppresses the production of chylomicrons, playing a previously unknown role in lipid metabolism that may contribute to the postprandial hypertriglyceridemia associated with apoA-V deficiency.


1984 ◽  
Vol 247 (6) ◽  
pp. G599-G610 ◽  
Author(s):  
P. Tso ◽  
D. S. Drake ◽  
D. D. Black ◽  
S. M. Sabesin

Previously, we demonstrated that the hydrophobic surfactant Pluronic L-81 (L-81) inhibits the intestinal formation and transport of chylomicrons (CM) but not of very low-density lipoprotein-sized (VLDL) particles. The present study was undertaken to determine whether infusion of egg lecithin results mainly in secretion of VLDL by the small intestine and whether L-81 has any effect on their formation and secretion. Intestinal fistula rats were infused intraduodenally at a rate of 3 ml/h with a lipid emulsion containing 20 mM egg lecithin and 19 mM sodium taurocholate for 8 h. This was then followed by another 8 h of infusion of a similar lipid emulsion but with 0.5 mg/h of L-81 added. Lymphatic lipid output was measured, and lymph lipoproteins were sized by use of electron microscopy. Whether L-81 was present or not, no significant difference was detected in the lymphatic triglyceride, phospholipid, or cholesterol outputs. Based on agarose gel electrophoresis, sizing of intestinal lymph lipoproteins, and also the determination of lipid in the intestinal lymph CM and VLDL as separated by ultracentrifugation, VLDL were the major lipoproteins present in lymph during the infusion of egg lecithin. Thus, intraduodenal infusion of egg lecithin in the rat results mainly in the transport of VLDL and is not affected by the administration of L-81. The results suggest that CM and VLDL are assembled separately by the enterocytes and indicate the usefulness of L-81 in further investigating the pathways and regulation of intestinal lipoprotein synthesis, assembly, and secretion.


1957 ◽  
Vol 191 (1) ◽  
pp. 179-184 ◽  
Author(s):  
George V. Vahouny ◽  
C. R. Treadwell

Time studies of the appearance of lipid fractions in the thoracic duct lymph of rats were performed following the administration of emulsions containing cholesterol, oleic acid and sodium taurocholate. The influence of added protein on lipid levels and the total nitrogen of lymph was also studied. Addition of albumin to administered saline was without effect on lymph flow, lipid fractions or total nitrogen. In those animals receiving cholesterol, oleic acid and taurocholate, in addition to albumin, a rapid increase in total lipid was evident during the initial 3 hours, followed by a gradual fall in this fraction to near preabsorptive levels at the end of 9 hours. Comparable changes were observed in the ester cholesterol, neutral fat and phospholipid fractions. Animals receiving a similar emulsion lacking albumin displayed less marked increases in the lipid fractions which were, however, prolonged throughout the experimental period. In contrast to the other lipid fractions in this group, the amount of lymph cholesterol for the 24-hour period was significantly greater than in the comparable group receiving albumin. During cholesterol absorption in both experimental groups, the increase in total lymph cholesterol was attributable almost entirely to an increase in the esterified fraction, which comprised between 84 to 92% of the absorbed sterol.


Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 233
Author(s):  
Atheer Zgair ◽  
Yousaf Dawood ◽  
Suhaib M. Ibrahem ◽  
Jong Bong Lee ◽  
Wanshan Feng ◽  
...  

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo.


Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 147 ◽  
Author(s):  
Jin Qiao ◽  
Danyang Ji ◽  
Shilin Sun ◽  
Guangyuan Zhang ◽  
Xin Liu ◽  
...  

We developed self-microemulsifying drug-delivery systems (SMEDDS), including bile salts, to improve the oral bioavailability of pueraria flavones (PFs). The physical properties of the SMEDDS using Cremophor RH 40, and bile salts as mixed surfactants at weight ratios of 10:0–0:10 were determined. The particle sizes of PFs-SMEDDSNR containing sodium taurocholate (NaTC) and Cremophor RH 40, and PFs-SMEDDSR containing Cremophor RH 40 were measured upon dilution with deionized water and other aqueous media. Dilution volume presented no remarkable effects on particle size, whereas dilution media slightly influenced particle size. PFs-SMEDDSNR and PFs-SMEDDSR provided similar release rates in pH-1.2 hydrochloride solution. However, the release rate of PFs-SMEDDSNR was faster than that of PFs-SMEDDSR in pH-6.8 phosphate buffer containing 20 mM NaTC and 500 U/mL porcine pancreas lipase. The pharmacokinetics and bioavailability were measured in rats. The oral bioavailability of PFs-SMEDDSNR was 2.57- and 2.28-fold that of a suspension of PFs (PFs-suspension) before and after the blockade of the lymphatic transport route by cycloheximide, respectively. These results suggested PFs-SMEDDSNR could significantly improve the oral relative absorption of PFs via the lymphatic uptake pathway. SMEDDS containing NaTC may provide an effective approach for enhancing the oral bioavailability of PFs.


Sign in / Sign up

Export Citation Format

Share Document