Absorption, Distribution and Excretion
In the small intestine, most triglycerides are broken down into monoglycerides, free fatty acids, and glycerol, and absorbed by the intestinal mucosa. Within the intestinal epithelial cells, resynthesized triglycerides aggregate with cholesterol and phospholipids to form globular structures, which are then encapsulated by proteins to form chylomicrons. Chylomicrons are transported via the lymphatic system to the thoracic duct and eventually into the venous system. Chylomicrons are cleared from the bloodstream as they flow through the capillaries of adipose tissue. Fat is stored in adipocytes until it is transported to other tissues as free fatty acids for cellular energy or integrated into the cell membrane. When 14C-labeled long-chain triglycerides are injected intravenously, 25% to 30% of the radiolabeled material appears in the liver within 30 to 60 minutes, and less than 5% remains after 24 hours. Small amounts of radiolabeled material are also found in the spleen and lungs. After 24 hours, nearly 50% of the radiolabeled material is excreted with carbon dioxide, leaving only 1% of the carbon-labeled material in brown adipose tissue. The radioactivity concentration in epididymal fat was less than half that in brown fat. Rats were fed an emulsion diet via gastric tube consisting of 95 parts triolein (trioleyl ester) and 5 parts 1-(14)C-triolein. Within 24 hours, 88% of 1-(14)C-triolein was detected in the lymph. In a previous study, four male rats (weighing 250 g) were orally administered [1-(14)C]triolein. Within 24 hours, the percentage of radioactive absorption ranged from 57% to 92% (mean = 78.2%). The percentage of absorbed radioactivity recovered from the thoracic duct lymphatic fat ranged from 51% to 83% (mean = 65.5%). Following intravenous injection of a single dose of [1-(14)C]triolein into fasted rats, higher uptake rates were observed in the liver, myocardium, gastric mucosa, and diaphragm. However, radioactivity in these tissues decreased significantly after 24 hours. Similar distribution patterns were observed in mice; however, significant radioactivity was observed in brown adipose tissue, white adipose tissue, and spleen even after 24 hours. For more complete data on the absorption, distribution, and excretion of trioleic glycerides (7 in total), please visit the HSDB record page. Metabolism/Metabolites In vitro experiments have confirmed that hepatic triglyceride lipase in ICR mouse plasma hydrolyzes trioleic glycerides. In vitro experiments assessed the metabolism of trioleic glycerides using ex vivo perfusion of rat liver and rat hind limbs. This allowed us to investigate lipid transfer between the two. Measurements of the fatty acid gradient between tissue beds without the addition of trioleic glycerides showed net removal of free fatty acids in both tissue beds. After the addition of 100 mg of trioleic glycerides (in the form of [(3)H]-glycerol-[(14)C]trioleic glycerides) to either reservoir of the system, the net production of free fatty acids at the posterior gradient significantly increased at 30 minutes. The outflow of this posterior free fatty acid exceeds one-third of the catabolism of trioleic acid esters. In experimental studies, embolization of the cerebral hemispheres with trioleic acid ester emulsion showed reversible magnetic resonance imaging (MRI) results in the subacute phase. This study aimed to investigate changes in major metabolites in trioleic acid ester emulsion-induced cerebral fat embolism using proton magnetic resonance spectroscopy (MRS). Trioleic acid ester emulsion was injected into the internal carotid artery of 19 cats, and multivoxel MRS was performed at 30 minutes, 1 day, and 7 days. In the control group, six cats were injected with saline. The levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), as well as the presence of lipids and lactate, were assessed using magnetic resonance spectroscopy. Semi-quantitative analyses of the NAA/Cr, Cho/Cr, NAA/Cho, and lipid/Cr ratios were performed, comparing the median metabolite ratios at each time point in the ipsilateral hemisphere with the corresponding values in the contralateral hemisphere and the control group. The NAA/Cr, Cho/Cr, and NAA/Cho ratios in the ipsilateral cerebral hemisphere of the embolization group at 30 minutes, 1 day, and 7 days were not significantly different from those in the contralateral cerebral hemisphere of the embolization group and the control group (P>0.05). Compared with the control group, the lipid/creatine ratio in the ipsilateral cerebral hemisphere of the embolization group was significantly increased (P=0.012 at 30 minutes, P=0.001 on day 1, and P=0.018 on day 7). Trioleic acid glyceride emulsion-induced cerebral fat embolism did not cause significant changes in the major brain metabolites during the acute phase, only an increase in the lipid/creatine ratio, suggesting that the lesions embolized by fat emulsion did not undergo significant hypoxic-ischemic changes. The effects of protopanaxadiol (PDG) and protopanatriol (PTG) ginsenosides isolated from American ginseng leaves on porcine pancreatic lipase activity were determined in vitro. PDG inhibited pancreatic lipase activity in a dose-dependent manner within the concentration range of 0.25–1 mg/mL. At a concentration of approximately 1 mg/mL, the inhibition rate of trioleic acid hydrolysis was approximately 83.2%. However, PTG did not show inhibitory activity. Therefore, we evaluated the anti-obesity activity of PDG in mice fed a high-fat diet. The results showed that PDG effectively prevented and treated obesity, fatty liver, and hypertriglyceridemia in mice fed a high-fat diet.

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Biological half-life
/Half-life/ 4.5 minutes.

Interactions
Intramuscular injection of tetracycline hydrochloride 250 mg/kg (rat) significantly reduced the intestinal absorption of trioleic acid glyceride administered via gastric perfusion. Oral administration of neomycin 2 g/kg twice daily reduced the intestinal absorption of (14)C-labeled trioleic acid glyceride in rats. This study aimed to evaluate the effect of dexamethasone on blood-eye barrier damage induced by trioleic acid glyceride emulsion using contrast-enhanced magnetic resonance imaging. 0.1 mL of trioleic acid glyceride emulsion was dissolved in 20 mL of physiological saline and injected into the carotid artery of 32 cats, with 12 cats in the treatment group and 18 cats in the control group. Thirty minutes after injection, a set of T1-weighted magnetic resonance images (T1WI) of the orbit before and after contrast enhancement were acquired. Each cat in the treatment group received 10 mg/kg of dexamethasone perfusion in the ipsilateral carotid artery, while each cat in the control group received 20 mL of physiological saline perfusion. Three hours after instillation of triolein emulsion, orbital T1-weighted imaging (T1WI) was performed again before and after contrast enhancement. Qualitative analysis was performed on the anterior chamber (AC), posterior chamber (PC), and vitreous body of the ipsilateral and contralateral eyes. Quantitative assessment and statistical comparison were performed on the signal intensity ratios of the ipsilateral eye relative to the contralateral eye in the first and second groups of T1WI images. Qualitative analysis showed no immediate contrast enhancement in the anterior chamber, posterior chamber, and vitreous body in the first and second groups of contrast-enhanced T1WI images. However, delayed contrast enhancement was observed in the anterior and posterior chambers of both groups of cats in the second group of pre-contrast-enhanced T1WI images. No enhancement or only slight delayed enhancement was observed in the vitreous body. Quantitative analysis showed that the signal intensity ratio of the posterior chamber (PC) in the treatment group was significantly lower than that in the control group in the second group of T1-weighted images (T1WI) (p = 0.037). There were no statistically significant differences in the anterior chamber (AC) and vitreous body between the treatment and control groups (p > 0.05). Contrast-enhanced magnetic resonance imaging showed increased vascular permeability of the posterior capsule after perfusion with triolein emulsion. Dexamethasone appeared to reduce disruption of the posterior capsule blood-aqueous barrier. Fat embolism (FE) is a poorly understood and often overlooked complication following skeletal trauma and certain orthopedic surgeries. Fat embolism can lead to severe lung injury and trigger fat embolism syndrome (FES). This study established a pulmonary fibrosis model in conscious rats using intravenous injection of neutral triolein to investigate the potential therapeutic effects of altering endogenous angiotensin II (Ang II) production or response on lung histopathology. One hour after triolein injection to induce pulmonary fibrosis, either the angiotensin I converting enzyme inhibitor captopril or the angiotensin II type 1 receptor blocker losartan were injected. Animals were sacrificed 48 hours later for histopathological evaluation, comparing lung histopathological changes in the drug treatment group and the control group treated with triolein only. Results showed that rats treated with triolein only exhibited severe diffuse lesions in their lung tissue. Severe diffuse inflammation was observed in the alveolar septa. Significant sloughing of bronchial mucosal epithelial cells was observed. Thickening of the vascular media in pulmonary arterioles and arterioles reduced luminal patency by 60% to 70%. Trichrome staining confirmed abundant collagen in the tunica media and adventitia, as well as collagen infiltration of the bronchial muscle layer. Treatment with captopril and losartan reduced inflammation, vasoconstriction, and pro-fibrotic effects observed at 48 hours (p<0.001). Post-treatment, vascular patency was maintained, and the volume and number of fat droplets decreased. The number of infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils decreased, and hemorrhage and collagen deposition were also significantly reduced (p<0.001). Pathological changes in the bronchial epithelium were also alleviated. These results suggest that drugs acting on the renin-angiotensin system may provide an effective and targeted treatment for fat embolism syndrome.
For more complete data on interactions of TRIOLEIN (6 drugs in total), please visit the HSDB record page.

[1]. Triolein reduces MMP-1 upregulation in dermal fibroblasts generated by ROS production in UVB-irradiated keratinocytes. J Dermatol Sci. 2017 Feb;85(2):124-130.

[2]. Triolein and trilinolein ameliorate oxidized low-density lipoprotein-induced oxidative stress in endothelial cells. Lipids. 2014 May;49(5):495-504.

Trioleic acid glycerides are triglycerides formed by esterification of the three hydroxyl groups of glycerol with oleic acid. Trioleic acid glycerides are one of the two components of lorenzo oil. It is both a plant metabolite and a metabolite of C. elegans. It is functionally related to oleic acid.
Trioleic acid glycerides have been studied for the treatment of adrenoleukodystrophy.
Trioleic acid glycerides have been reported to be present in ginseng, Grifola frondosa, and other organisms with relevant data.
TG(18:1(9Z)/18:1(9Z)/18:1(9Z)) is a metabolite found or produced in Saccharomyces cerevisiae.
(Z)-9-octadecenoic acid 1,2,3-propanetriester.
See also: Coix seed (partial).

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Therapeutic Use
/The aim of this study is/to identify asymptomatic X-linked adrenoleukodystrophy boys with normal magnetic resonance imaging (MRI) and to evaluate the efficacy of 4:1 glycerol. The effect of trioleoglycerate trierucate (lorenzo oil) on disease progression. High-risk boys were screened by plasma very long chain fatty acid (VLCA) assays, and a total of 89 boys (mean baseline age ± standard deviation: 4.7 ± 4.1 years; age range: 0.2–15 years) were included. All boys received lorenzo oil treatment with moderate fat restriction. Plasma fatty acids and clinical status were followed up for 6.9 ± 2.7 years. Changes in plasma hexacosanoid acid (HLA) levels were assessed by measuring the area under the curve (AUC), and its association with the occurrence of MRI and neurological abnormalities was evaluated using a proportional hazards model. Among the 89 boys, 24% had MRI abnormalities, and 11% had both neurological and MRI abnormalities. Abnormalities occurred only in 64 patients aged 7 years or younger at the start of treatment. The occurrence of MRI abnormalities was significantly associated with elevated plasma HLA levels. (For every 0.1 μg/mL increase in the area under the curve (AUC) of hexacosanoic acid (LAA) levels (length-corrected), the risk ratio for MRI abnormalities in the entire group was 1.36; P = 0.01; 95% confidence interval 1.07–1.72.) Results were similar in patients aged 7 years and younger (P = 0.04). In this single-arm study, lorenzo oil reduced LCA levels and was associated with a reduced risk of MRI abnormalities. We recommend lorenzo oil therapy for asymptomatic X-linked adrenoleukodystrophy boys with normal brain MRI findings.
X-linked adrenoleukodystrophy (X-ALD) is a hereditary peroxisome metabolic disorder characterized by insufficient β-oxidation of saturated very long-chain fatty acids (VLCFAs). The accumulation of these fatty acids in various tissues and fluids leads to progressive central and peripheral demyelination, as well as adrenal insufficiency and hypogonadism. Seven variants of the disease have been described, with the cerebral form being the most common in children. The recommended treatment is the use of a triglyceride/triglyceridylglycerol mixture, namely lorenzo oil (LO), combined with a low-VLCFA diet. However, this therapy is only effective in asymptomatic patients to prevent symptom progression. This study evaluated the biochemical changes in children with cerebral X-ALD (CCER) and asymptomatic clinical X-ALD patients receiving a low-fat diet combined with a VLCFA restriction diet. We observed that, compared with at diagnosis, plasma hexacosanoic acid concentrations and hexacosanoic acid/docosahexacosanoic acid ratios were significantly reduced during treatment in CCER patients. Plasma hexacosanoic acid levels were significantly reduced compared with at diagnosis and returned to normal only in asymptomatic patients receiving a low-fat diet. The reduction in hexacosanoic acid levels was greater in asymptomatic patients than in CCER patients. These results suggest that a low-fat diet has good biochemical efficacy in patients with asymptomatic X-ALD. It can be speculated that this may be related to the prevention of neurological symptoms in this group of patients receiving lorenzo oil (LO). This study aimed to investigate the potential therapeutic effects of using a synthetic oil containing trioleic and trioleic acids (lorenzo oil) to reduce plasma levels of very long-chain fatty acids (C26:0) and using docosahexaenoic acid (DHA) ethyl ester to increase DHA levels in erythrocytes (RBCs) in four patients with Zelvig syndrome. Gas chromatography/mass spectrometry (GC/MS) was used to continuously monitor changes in plasma C26:0 levels and DHA levels in erythrocyte membranes. After patient death, the fatty acid composition of the brain and liver of each patient was analyzed. Dietary supplementation with lorenzo oil reduced plasma C26:0 levels. Early administration of lorenzo oil was more effective, and the efficacy was independent of the time of administration. After oral administration of DHA, DHA was integrated into erythrocyte membrane lipids, and its levels remained elevated for several months. The final DHA level was related to the duration of administration but not to the time of treatment initiation. Patients who received treatment had higher DHA levels in the brain and liver than those who did not receive treatment. Early initiation of Lorenzo oil and long-term DHA intake may be beneficial for patients with Zelvig syndrome.

C57H104O6

885.4321

884.783

122-32-7

5497163

Colorless to light yellow liquid

0.9±0.1 g/cm3

818.7±55.0 °C at 760 mmHg

-5,5°C

302.7±31.5 °C

0.0±3.0 mmHg at 25°C

1.477

23.71

0

6

53

63

1010

0

O(C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)C([H])(C([H])([H])OC(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)C([H])([H])OC(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O

PHYFQTYBJUILEZ-IUPFWZBJSA-N

InChI=1S/C57H104O6/c1-4-7-10-13-16-19-22-25-28-31-34-37-40-43-46-49-55(58)61-52-54(63-57(60)51-48-45-42-39-36-33-30-27-24-21-18-15-12-9-6-3)53-62-56(59)50-47-44-41-38-35-32-29-26-23-20-17-14-11-8-5-2/h25-30,54H,4-24,31-53H2,1-3H3/b28-25-,29-26-,30-27-

propane-1,2,3-triyl trioleate

Glyceryl trioleate Lorenzo oil Lorenzo's oil Oleic triglyceride Raoline Triolein

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~112.94 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)