Rats fed rapeseed oil (46.2% erucic acid) for 20 wk had 2-fold heart sphingomyelin content incr. After high erucic rapeseed oil, 22:1 was incorporated into cardiolipin (5.6%) & sphingomyelin (10.5%)...
Male Wistar rats were fed with erucic acid for 20 days. Erucic acid was incorporated into diphosphatidylglycerol and sphingomyelin in heart and liver. The level of erucic acid incorporated into triacylglycerols and free fatty acids in the heart was higher than in the liver.
A study with cultured fibroblasts from normal controls and Zellweger fibroblasts showed that peroxisomes play an important role in the chain-shortening (beta-oxidation) of erucic acid.
Male Sprague-Dawley rats were fed with diets containing different levels of erucic acid (22:1 n-9) for 1 wk. An incr in dietary 22:1 n-9 resulted in significantly incr myocardial lipidosis as assessed histologically and by an accumulation of 22:1 n-9 in heart lipids; there was no incr in cardiac triacylglycerol except when high erucic acid rapeseed (42.9% 22:1 n-9) oil was fed.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
职业性肝毒素 - 第二性肝毒素:在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The aim of this study was to evaluate the ability of propionyl-L-carnitine to prevent cardiac damage induced by erucic acid. Rats were fed for 10 days with normal or 10% erucic acid-enriched diets with or without propionyl-L-carnitine intraperitoneally injected, (1 mM/kg daily, for 10 days). The erucic acid diet produced increases in triglycerides (from 5.6 to 12.4 mg/gww, P less than 0.01), and free fatty acids (from 2.0 to 5.1 mg/gww, P less than 0.01), but no changes in phospholipids. When the hearts were perfused aerobically with an isovolumic preparation there was no difference in mechanical activity. On the contrary, when pressure-volume curves were determined, the pressure developed by hearts from the erucic acid-treated rats were reduced. Independent of diet, propionyl-L-carnitine treatment always produced positive inotropy. This was concomitant with improved mitochondrial respiration (RCI 5.1 vs 9.3, P less than 0.01), higher tissue ATP content (10.3 vs 18.4 mumol/gdw P less than 0.01) and reduction of triglycerides (12.4 vs 8.0 mg/gww, P less than 0.01). These data suggest that propionyl-L-carnitine, when given chronically, is able to prevent erucic acid-induced cardiotoxicity, probably by reducing triglyceride accumulation and improving energy metabolism.
Seven groups of 24 /male Wistar/ rats were /daily/ fed diets containing 0, 5, 10, 15, 25 or 30 cal% rapeseed oil /(relative concn of erucic acid were 0, 5.5, 11.0, 16.5, 22.0, 27.5 and 33.0 % of dietary fat respectively)/. All diets were made up to 40 cal% fat with sunflower seed oil. Eight animals from each group were killed after 3 days, 6 days, and 32 wk. In each case the skeletal muscles, heart, diaphragm and adrenals were examined microscopically. In addition the thyroids, testicles, pancreas, spleen, liver and kidneys from animals killed after 32 wk were microscopically examined. Growth: no clear relationship between body weight gain and erucic acid treatment was observed. The average body weight of animals fed 30 cal% rapeseed oil was consistently the lowest, and analysis of variance showed that this difference was almost significant by the end of the test. However, the average body weight of animals fed 20 and 25 cal% rapeseed oil were consistently the highest. No clear relationship between body weight and rapeseed oil treatment was observed. Organ weights: Some significant differences were observed between controls and animals treated with at least 15 cal% rapeseed oil. However, no clear treatment related differences were observed. Pathology: In the animals killed after 3 or 6 days, all animals fed rapeseed oil showed lipidosis of the heart, skeletal muscle, diaphragm and adrenals. The severity of lipidosis incr with the level of rapeseed oil. No other abnormalities were observed. In the animals killed after 32 wk, no treatment-related effects were observed in the skeletal muscle, thyroid, pancreas, or liver of any groups. Effects were observed in the kidneys - slight tubular dilation and incr luminal debris was observed in the renal tubules. These effects were most noticeable in the top dose group. Enlargement of the adrenal cortical cells was observed at 10 cal% and above; severity incr with dose. Cardiac changes were also observed, consisting of minimal lipidosis, foci of myocytolysis showing mononuclear cell proliferations, thickening of the reticular muscle fibre sheath, incr interstitial connective tissue elements and aggregates of Anitskow cells. These effects incr in severity with incr doses of rapeseed oil (especially above 10 cal%). Minimal deg of these changes were also observed in 2 control animals.
Weanling female /Sprague-Dawley/ rats were fed /daily/ diets containing 0.5%, 5%, 10% or 20% of one of the following fats/oils: coconut oil, butter, tallow, lard, olive oil, rapeseed oil, cottonseed oil, corn oil, soybean oil, sunflower seed oil ... When rats were 50 days old, they were given a single oral dose of dimethylbenz [a] anthrene (DMBA). The diets were continued for 4 months ... More than 85% of the animals /in 20% dose levels/ developed tumors in all groups except those on tallow (80%) and rapeseed oil (77%) ... There tended to be more tumors/rat in animals fed unsaturated fats ... Most of the tumors were adenocarcinomas. /Rapeseed oil/
Eight groups of 5 /male Wistar/ rats were fed daily diets (ad libitum) containing 15% lipids for 12 days. The treatment groups were as follows: BR+: High brassidic acid (28% of lipids), low calcium (0.4%); BR-: Low brassidic acid (1.2% of lipids), low calcium; Br+ Ca: High brassidic acid, high calcium (9.2%); BR- Ca: Low brassidic acid, high calcium; ER+: High erucic acid (28% of lipids), low calcium; ER-: Low erucic acid (1.4% of lipids), low calcium; ER+ Ca: High erucic acid, high calcium; ER- Ca: High erucic acid, high calcium. /The remainder of lipids in each group were made up with maize oil./ There were no significant differences in food consumption alone or weight gain alone. However, if weight gain was adjusted to food consumption, it showed that weight gain for brassidic acid groups was lower in low calcium groups. Weight gain was unaffected for erucic acid groups. All 4 erucic acid groups showed similar levels of heart triglycerides, and C22:1. The hearts showed a mild lipidosis as compared to control rats ... For brassidic acid groups, low calcium decr the heart triglyceride levels. In addition, the triglyceride and C22:1 heart levels were higher in the 2 high brassidic acid groups.
After injection (14)C-erucic acid emulsion in rapeseed oil, highest cconcn found in lipids of rat liver, followed by spleen & kindey. Fatty acid uptake level into lipids was small in brain, testes & seminal vesicles.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
二十碳烯酸被掺入到雄性大鼠心脏和肝脏的二磷脂酰甘油和鞘磷脂中,这些大鼠连续二十天喂食二十碳烯酸。
Erucic acid was incorporated into diphosphatidylglycerol & syhingomyelin in heart & liver of male rats fed erucic acid for 20 days.
Wistar rats were given a single oral dose of 560 mg erucic acid (ethyl ester) ... Erucic acid levels in the stomach and small intestine reached a max 2 hr after dosing (40% of the dose). Erucic acid levels in the colon reached a max 8 hr after dosing (50% of the dose). This suggested that erucic acid was poorly absorbed. Erucic acid levels in cardiac blood also reached a max 2 hr after dosing (14% of total fatty acids, against a background level of 2.5%).
Male rats (Wistar strain) were iv injected with a mixture of free (14)C-labeled erucic and (3)H-labeled oleic acid. after 2, 4, 8, 16 and 30 min, radioactivity was examined in blood, liver, heart, kidneys and spleen. At all times studied, the majority of radioactivity was found in the liver, primarily as triglycerides (60% of radioactivity in total lipids) and as phospholipids (20 to 30%). In the other organs tested, radioactivity was found 10 to 15 times lower than in liver. In the heart, (14)C was 3 to 4 times higher than (3)H. More than 80% was recovered in tri-glycerides. In spleen and kidneys, the (14)C:(3)H ratio was particularly high in free fatty acids and monoglycerides. In kidneys, 60% of (14)C was present as nervonic acid in monoglycerides and 40% in phospholipids, suggesting that the mononervonin formed was used for phospholipid biosynthesis.
[EN] AGENTS AND METHODS FOR TREATING DYSPROLIFERATIVE DISEASES<br/>[FR] AGENTS ET MÉTHODES POUR TRAITER DES MALADIES DYSPROLIFÉRATIVES
申请人:MEMORIAL SLOAN KETTERING CANCER CENTER
公开号:WO2019161345A1
公开(公告)日:2019-08-22
Compounds are described with the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and n are defined as anywhere herein, which are useful for the treatment of cancer and other dysproliferative diseases.
Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.
[EN] BIOACTIVE CONJUGATES FOR OLIGONUCLEOTIDE DELIVERY<br/>[FR] CONJUGUÉS BIOACTIFS POUR L'ADMINISTRATION D'OLIGONUCLÉOTIDES
申请人:UNIV MASSACHUSETTS
公开号:WO2017030973A1
公开(公告)日:2017-02-23
Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.
UNSATURATED FATTY ACID MONOESTERS AND DIESTERS ON ASCORBIC ACID AND COSMETIC USES THEREOF
申请人:Poigny Stéphane
公开号:US20120076744A1
公开(公告)日:2012-03-29
The present invention relates to a compound with the following general formula (I):
in which: R
1
is a hydrocarbon chain of an unsaturated fatty acid from C
12
to C
24
including at least one unsaturation; and R
2
and R
3
are, independently or simultaneously: a hydrogen or a C
1
-C
3
alkyl or a phenyl; and R
4
: a hydrogen atom or COR
1′
, where R
1′
is a hydrocarbon chain of an unsaturated fatty acid from C
12
to C
24
including at least one unsaturation, advantageously 1 to 6 and preferably 1 to 4.
[EN] 2-SULFANYL-BENZOIMIDAZOL-1-YL-ACETIC ACID DERIVATIVES AS CRTH2 ANTAGONISTS<br/>[FR] DERIVES DE L'ACIDE 2-SULFANYL-BENZOIMIDAZOL-1-YL-ACETIQUE EN TANT QU'ANTAGONISTES DE CRTH2
申请人:ACTELION PHARMACEUTICALS LTD
公开号:WO2006021418A1
公开(公告)日:2006-03-02
The invention relates to 2-sulfanyl-benzoimidazol-1-yl-acetic acid derivatives and their use as potent 'chemoattractant receptor-homologous molecule expressed on Th2 cells' antagonists in the treatment of prostaglandin mediated diseases, to pharmaceutical compositions containing these derivatives and to processes for their preparation.