Inhibition of hepatic sterol and squalene biosynthesis in rats fed di-2-ethylhexyl phthalate

Di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer, was found to be an inhibitor of the biosynthesis of hepatic nonsaponifiable lipids in the rat. The addition of DEHP at levels of 0.5% or 1.0% to a stock diet of rats resulted in a decreased conversion of acetate-1-¹⁴C and mevalonate-5-³H into squalene, C₃₀ sterols, and C₂₇ sterols by liver minces or slices, in vitro. In studies conducted with 0.5% DEHP feeding from 2 to 11 days, the degree of inhibition was found to increase with the duration of DEHP feeding; the inhibition of³H-mevalonate conversion to squalene and sterols developed more slowly, being reduced to ca. 70% of control values in 11 days, whereas¹⁴C-acetate conversion was reduced to ca. 35% of control values during the same period.³H-mevalonate conversion to sterols and squalene was, however, found to be suppressable to the same extent as¹⁴C-acetate conversion when diets containing 1.0% DEHP were fed for 18 days. The inhibitory effect of dietary DEHP on sterol and squalene biosynthesis from¹⁴C-acetate and³H-mevalonate by rat liver preparations is unlikely to be accounted for by the negative feedback of cholesterol secondary to hepatic sterol accumulation since, in these studies, hepatic total lipid and hepatic total sterol levels were simialr in control and DEHP-fed rats.     

Migration of plasticizer di-2-ethylhexyl phthalate from PVC packaging material into cured meat

利用增塑剂DEHP的皂化反应,采用膜/肉接触的比色管模式和气相色谱法,研究了温度、时间、脂肪含量和加工方式等因素对PVC膜中的增塑剂DEHP向广式腊肠迁移的影响。结果表明：随着温度的升高,时间的延长,脂肪含量的增加,DEHP向肉中的迁移量均会增大;在紫外照射、微波辐射和高温蒸煮等条件下,DEHP的迁移量也会增加,其中微波辐射的作用较为明显,如微波照射18 s后,DEHP的迁移量高达189.3342 mg/kg,紫外光照射48 h后,迁移量是173.5921 mg/kg。同时研究了DEHP迁移溶出后,PVC膜的拉伸性能、断裂伸长率、透氧率和透湿率等性能的变化。结果表明：当增塑剂DEHP迁移溶出后,PVC膜的阻隔性和力学性能也发生了明显的变化,随着时间的延长、迁移量的增大,其PVC膜的拉伸强度逐渐升高,断裂伸长率逐渐降低,PVC膜的透氧率和透湿率也降低。     

Alteration of hepatic phospholipids in rats and mice by feeding di-(2-ethylhexyl)adipate and di-(2-ethylhexyl)phthalate

Effects of di-(2-ethylhexyl)adipate (DOA) and di-(2-ethylhexyl)phthalate (DEHP), plasticizers for polyvinylchloride products, on concentrations and compositions of hepatic phospholipids were studied in rats. When administered to rats at a 2% level for 2 wk, both DOA and DEHP caused a hepatomegaly, an increase in hepatic phospholipids and a decrease in the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE). In the comparable study with mice, the alkyl moiety of DOA was found to be responsible for these alterations. DOA and DEHP specifically altered fatty acid compositions of PC and PE: there was an increase in oleic and palmitic acids and a decrease in stearic and docosahexaenoic acids in PC and an increase in arachidonic acid at the expense of docosahexaenoic acid in PE. In addition, DOA caused an increase in the trienoic and tetraenoic molecular species in PC and an increase in the 1-palmitoyl-2-arachidonyl (16∶0//20∶4) species in PE. Thus, the effects of DOA on the lipid dynamics resembled those observed with DEHP, although the magnitude was slightly moderated.     

c-Jun氨基末端激酶在邻苯二甲酸二(2-乙基)己酯诱导的尿道下裂大鼠阴茎组织中的表达

目的研究c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)在邻苯二甲酸二(2-乙基)己酯[di(-2-ethyl-hexyl)phthalate,DEHP]诱导的尿道下裂大鼠阴茎组织中的表达变化,探讨尿道下裂发生的机制。方法将孕12 d(gestation day,GD12)的SD孕鼠随机分为2组:实验组[将DEHP溶于1.5 ml大豆油中灌胃大鼠,750 mg/(kg.d)]和对照组(以1.5 ml大豆油灌胃大鼠),每组20只,自GD12～GD19连续每天定时给药1次。各组分别取10只孕鼠正常分娩,雄性仔鼠出生后30 d,计数每窝产雄性活仔数,称量体重,并测量肛门生殖器距离(anogenital distance,AGD),逐个检查雄鼠的阴茎弯曲度和尿道开口部位,判断有无尿道下裂;其余孕鼠在怀孕第20天行剖宫产取出胎鼠,采用实时定量PCR(qPCR)和免疫组化法分别检测雄性胎鼠阴茎组织中JNK1和JNK2 mRNA和蛋白的表达水平。结果雄性仔鼠出生后30 d,实验组与对照组比较,每窝产雄性活仔数、雄性仔鼠的体重及AGD均有明显减少或缩短(P均<0.001);实验组尿道下裂发生率约为30.6%。与对照组比较,实验组胎鼠阴茎组织中JNK1和JNK2mRNA的水平明显增加(P<0.05),磷酸化JNK1和JNK2蛋白的表达水平有增加的趋势。结论 DEHP诱导的先天性尿道下裂可能与胎鼠阴茎组织中JNK通路异常表达有关。     

Effect of dietary di-2-ethylhexyl phthalate on oxidation of14C-palmitoyl CoA by mitochondria from mammalian heart and liver

Oxidation of [1-¹⁴C] palmitoyl CoA by heart and liver mitochondria from rats fed dietary di-2-ethylhexyl phthalate (DEHP) was investigated in vitro. Oxidation of¹⁴C-palmitoyl CoA to¹⁴CO₂ increased two- to threefold in hepatic mitochondria from rats fed 0.1% DEHP for 2 to 3 days; this increase appeared to be a maximum response since similar data were obtained using hepatic mitochondria from rats receiving 0.5% or 1.0% DEHP in the diet. The response of hepatic mitochondria to DEHP was found to continue throughout the duration of 35-day trials in which 1.0% DEHP was fed. In contrast to hepatic mitochondria, the oxidation of¹⁴C-palmitoyl CoA by heart mitochondria decreased ca. 40% upon addition of 0.1% or 0.5% DEHP to the diet; this effect of DEHP on heart mitochondria was not sustained beyond ca. 8 days of DEHP feeding. Limited studies were also performed in rabbits and pigs. Oxidation of¹⁴C-palmitoyl CoA was increased ca. twofold in hepatic mitochondria from rabbits fed 1% dietary DEHP for 12 days and in hepatic mitochondria from pigs that received 5 doses of DEHP (0.8g/kg) at 12-hr intervals; the oxidation¹⁴C-palmitoyl CoA by heart mitochondria from these same animals was unchanged in the rabbit but increased an average of 37% in the pig. DEHP feeding to rats was associated with increased yields of hepatic mitochondrial protein; standardized preparations of heart mitochondria were not similarly affected.     

Effects of di-(2-ethylhexyl) phthalate (DEHP) released from laboratory equipments

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in polyvinyl chloride (PVC) manufacturing and is an endocrine disrupter. DEHP was released from laboratory tubing and resins during solvent extraction of natural plants to isolate skin depigmenting compounds. Contamination of DEHP significantly interfered with the purification of depigmenting compounds, since DEHP showed high depigmenting activity (IC₅₀=24 μM) and did not show cell toxicity up to 20 μM. Release of DEHP depended on the composition of tubing materials and solvents used in the extraction process. This result provides practical information for the proper selection of laboratory materials and solvents especially in the extraction and isolation of skin depigmenting compounds for cosmetic ingredients.     

Effect of dietary di-2-ethylhexyl phthalate on lipid biosynthesis in selected tissues from the rat,in vitro

Di-2-ethylhexyl phthalate (DEHP), a plasticizer commonly used in the production of polyvinyl chloride plastics, has become an environmental pollutant. At the present time, the biological significance of phthalates in the environment is unknown. In the present studies, we observed that addition of DEHP to a stock diet of rats resulted in marked effects on incorporation of¹⁴C-acetate into lipid by liver and kidney slices; other organs, such as heart, testes, and aorta were unaffected. Incorporation of¹⁴C-acetate into total lipid of liver (dpm/mg wet wt) from rats, fed 0.5% or 1.0% DEHP for 10 or 18 days, respectively, was decreased to ca. 50% of control values. The decreased incorporation into liver lipid is not attributable to any one lipid fraction, inasmuch as incorporation into the phospholipid, sterol+diglyceride, free fatty acid, triglyceride, and sterol ester+hydrocarbon fractions was decreased 30–70% with respect to controls. In addition, the percent distribution of¹⁴C-acetate among the individual phospholipids was ca. 25% lower in phosphatidyl choline of the DEHP-fed rats. In rats fed 0.5% DEHP, incorporation of¹⁴C-acetate into total lipid of kidney was similar to control values, but incorporation into the triglyceride and sterol ester+hydrocarbon fraction was decreased 30–40%, whereas incorporation into the sterol+diglyceride fraction was increased 38%. Livers from DEHP-fed rats were ca. 20% larger than livers from control rats and, at the 0.%% level of DEHP feeding, testes wts were elevated; no significant changes were noted in wts of spleen, heart, aorta, kidney, or body wt gains in rats fed DEHP. These studies emphasize a subtle toxicity of phthalate esters not previously reported and emphasize the need for further biochemical studies to evaluate the effect of phthalates on biological systems.     

Phase separation in the synthesis of styrene–divinylbenzene copolymers with di-2-ethylhexyl phthalate as diluent

Phase separation by suspension copolymerization of styrene–divinylbenzene (DVB) with di-2-ethylhexyl phthalate (DOP) as diluent was investigated using equilibrium swelling, swelling rate, apparent densities, and mercury porosimetry. The copolymer prepared in the absence of DOP is heterogeneous, showing that a phase separation exists in the polymerization system, and, in the presence of DOP, the propagating copolymer separates earlier. Furthermore, with increasing amounts of DVB, phase separation occurs earlier than gelation, which causes a sudden increase in the amount of pores about 200–500 Å in diameter corresponding to the interstices between the microspheres.     

The incorporation of orally fed radioactive γ-linolenic acid and linoleic acid into the liver and brain lipids of suckling rats

The incorporation of radioactivity from orally administered gamma-linolenic acid-1--14C and linoleic acid--3H into the liver, plasma, and brain lipids of suckling rats was studied. Significantly more radioactivity from the former compound was incorporated into the liver and brain lipids 22 hr after dosing. The distribution of the radioactivity in the fatty acids of the liver and brain lipids was different for each isotope. Most of the -3H was still associated with linoeic acid, whereas most of the -14C was in the 20:3 and 20:4omega6 fractions. These results suggest that the desaturation of linoleic to gamma-linolenic acid in vivo is a rate-limiting step in the conversion of linoleic to arachidonic acid.     

The effect of feeding di-(2-ethylhexyl) phthalate (DEHP) on the lipid metabolism of laying hens

Di-(2-ethylhexyl)phthalate (DEHP), a commonly used plasticizer, is now seen as an environmental pollutant. DEHP has been found to inhibit lipid and sterol synthesis in rats and mice. The effects of DEHP on various aspects of lipid metabolism were examined in chickens. White Leghorn laying hens were fed either a standard laying mash control diet (C) or the control diet containing 1% DEHP (DEHP) or 1% DEHP and 5% tallow (DEHP-T) for 28 days. DEHP and DEHP-T lowered feed consumption 10% but did not significantly affect body weight. After 3 weeks on the diets, egg production was 15–20% less in DEHP-T than in C and DEHP hens. No differences were observed in egg weight, percent shell, white or yolk among the groups. DEHP and DEHP-T did not alter egg lipid or egg cholesterol concentrations. DEHP and DEHP-T lowered plasma lipid concentration about 20% and free and total cholesterol 20–30%. Liver weights increased, being 30, 34 and 39 g for C, DEHP and DEHP-T hens, respectively, after 28 days. Total liver lipid and cholesterol increased 19% and 26% in DEHP hens and 54% and 79% in DEHP-T hens when compared to controls. In contrast, the fat content of pectoralis major muscle decreased significantly in DEHP and DEHP-T hens. These results, in showing that DEHP alters plasma and tissue cholesterol but not yolk cholesterol, demonstrate again that egg cholesterol is remarkably resistant to alteration by dietary means.     

The effect of di-2-ethylhexyl phthalate on the thermo-oxidative ageing of poly(vinyl chloride)/epoxidized natural rubber blends

The effect of di-2-ethylhexyl phthalate (DOP) plasticizer on the degradation behaviour of 50/50 poly(vinyl chloride)/epoxidized natural rubber (PVC/ENR) blend was studied by long-term exposure to ambient conditions (27–30°C) in the laboratory. While the unplasticized blend showed obvious changes in physical properties such as hardening, loss of elasticity and embrittlement, the plasticized blend retained its properties. Thermo-oxidative ageing studies were carried out by evaluating the mechanical properties before and after ageing in an air oven at 80°C for 168 h. The relatively rapid degradation of PVC/ENR blend has been attributed to the high concentration of epoxy groups and the occurrence of ring-opening reactions to form ether crosslinks. It was found that the plasticizer confers adequate stabilization upon the addition of a certain threshold amount. The optimum amount of plasticizer required to adequately stabilize the blend is 20 phr. Above this there is a tendency for plasticizer migration to occur. The use of an antioxidant in conjunction with the plasticizer further stabilizes the blend. The general trend is of decrease in mechanical and physical properties with increase in DOP concentration. In addition, ease of processing also increases as indicated by the torque maxima and minima obtained from the Brabender plastograms.     

Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters

The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) inhibited (30–70%) hepatic sterologenesis from¹⁴C-acetate and¹⁴C-mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of¹⁴C-acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35–70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P<0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of³H-oleate into di- and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed. These studies are in partial fulfillment of the requirements for a Doctorate degree in Medical Sciences, McMaster University, Hamilton, Ontario, Canada.     

Assessment of di-(2-ethylhexyl)phthalate (DEHP) Removal in a Rotating Biological Contactor and Activated Sludge Process Treating Domestic Wastewater

Di-(2-ethylhexyl)phthalate (DEHP) is one of the most representative persistent micro-pollutants detected in the sewage sludge. In the present study, the presence of DEHP and its removal in various treatment units of a sewage treatment plant (STP) including an attached growth biological system i.e., a rotating biological contactor (RBC) and a suspended growth biological system i.e., activated sludge process (ASP) were investigated. Representative samples of sewage and sludge were collected at each stage of the STP for 2 years to explore the DEHP flow in the dissolved (DEHP_d) and adsorbed (DEHP_a) phases. The combination of RBC with a final clarifier was responsible for 50.4 and 58.2% of DEHP_d and DEHP_a removals, respectively. Both DEHP_d and DEHP_a removals were greater in RBC compared to ASP, demonstrating that an attached growth biological system is more efficient in the removal of DEHP compared to the suspended growth biological system. A good correlation between DEHP and organic matter removal was observed by using Pearson-correlation matrix approach.     

Behavior of a synergistic system in the extraction of Pr(III) from chloride medium using di-2-ethylhexyl phosphoric acid and 2-ethylhexylphosphonic mono-2-ethylhexyl ester

This paper will investigate the synergistic solvent extraction of extracted Pr from a chloride medium, using a mixture of two acidic extractants, namely 2-ethylhexylphosphonic mono-2-ethylhexyl ester (P507, HA) and di-2-ethylhexyl phosphoric acid (P204, HB) in kerosene. The stoichiometry of the extracted species was characterized by a classical lg–lg plot analysis. The composition of the extracted complexes has been determined as Pr(HA₂)(HB₂)₂. Moreover, the differences of the extraction behavior from sulfuric and chloride medium were discussed in detail. The values of equilibrium constant and thermodynamic parameters such as △G, △H, and △S were also calculated. A cation-exchange mechanism was proposed and further clarified by slope analysis and IR spectra.     

Inhibition of acyl CoA: Cholesterol acyltransferase and sterologenesis in rat liver by diazepam,In vitro

Diazepam, a commonly prescribed tranquilizer, was found to inhibit cholesterol biosynthesis in rat liver minces; inhibition appeared to occur at multiple post-mevalonate sites. Diazepam also inhibited cholesterol esterification by acylCoA:cholesterol acyltransferase in isolated liver microsomes and minces. Liver minces incubated with [¹⁴C] oleate demonstrated increased uptake of the fatty acid and a greater incorporation of the substrate into triglycerides, diglycerides and phospholipids when diazepam was present. The results suggest possible mechanisms for the hypocholesterolemic effect of diazepam in experimental animals and for the elevation of triglycerides and very low-density lipoproteins in man and the rat.     

Extraction of Gd,Tb, and Dy from nitrate media with a mixture of technical di-2-ethylhexyl phosphoric acid and tributylphosphate

Theoretical Foundations of Chemical Engineering - The extraction of medium–heavy rare-earth elements, such as gadolinium (Gd), terbium (Tb), and dysprosium (Dy), with extractant mixtures that...     

Inhibition of desaturation of stearic acid in livers of rats fed ethionine

The effect of ethionine on the conversion of stearic acid to oleic acid was studied. Rats were fed essential fatty acid (EFA) deficient diet for three weeks, after which time half the animals were fed 0.25% DL-ethionine for nine additional days. Seventeen hours prior to killing, they were fed a slurry of the diet containing 18-¹⁴C-stearic acid. Liver triglycerides and phospholipids were extracted and separated and their fatty acid composition and the distribution of radioactivity between stearic and oleic acid was determined. In the tissues studied, oleic acid was maintained at control levels in ethionine-fed rats, but eicosatrienoic acid was significantly depressed. Distribution of radioactivity and specific activity of oleic acid in the triglycerides and phospholipids were significantly reduced by the analogue. In vitro studies of desaturation and chain elongation reactions, with liver microsomes, using 18-¹⁴C-stearic and 1-¹⁴C-linoleic acids as substrates, showed that ethionine depressed the synthesis of oleic acid from stearic and γ-linolenic from linoleic acid. Elongation of linoleic adie to a 20∶2 fatty acid was unaffected by ethionine. Therefore, the results showed that ethionine inhibited desaturation of stearic to oleic acid in vivo and in vitro and probably also impaired the desaturation of oleic to octadeca-6, 9-dienoic acid. Maintenance of control levels of oleic acid in the tissues of ethionine-fed, EFA deficient rats suggested the presence of synthetic pathways for oleic acid other than via desaturation of stearic acid. Presented in part at the AOCS Meeting, San Francisco, April 1969.     

邻苯二甲酸二乙基己酯对金鲫鱼脑组织和肾脏的氧化损伤作用

研究了邻苯二甲酸二乙基己酯(DEHP)对金鲫鱼脑组织和肾脏的氧化损伤程度及其发生机制.结果表明,DEHP会造成金鲫鱼脑组织和肾脏的氧化损伤,随着DEHP浓度的升高,超氧化物歧化酶活力先升高后降低,丙二醛含量不断上升,呈明显的剂量一效应关系.