Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate

Background： To induce peroxisomal proliferator-activated receptor α（PPARα） expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate（2-（4-chlorophenoxy）-2-methyl-propanoic acid, ethyl ester）, on fatty acid oxidation was examined at ful-term delivery（0 h） and 24 h after delivery in this study.Each group of pigs（n = 10） was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were col ected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.Results： HPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow（~4.2 μg/m L）and its offspring（~1.5 μg/m L）. Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased（P 〈 0.01）^14C-accumulation in CO2 and acid soluble products 2.9-fold from [1-^14C]-oleic acid and 1.6-fold from[1-^14C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase（CPT）and acyl-Co A oxidase（ACO） activities by 36% and 42% over controls（P 〈 0.036）. The m RNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate（P 〈 0.0001） but no differences were detected for ACO and PPARα m RNA between the two groups.Conclusion： These data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.

Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets

To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.

Subnormal Serum Liver Enzyme Levels:A Review of Pathophysiology and Clinical Significance

Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease.Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia,Wilson's disease,deficiencies of divalent ions,or malnutrition.Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis,the use of certain medications,and in bone disease.Finally,subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia.The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.

Biosorption of clofibric acid and carbamazepine in aqueous solution by agricultural waste rice straw

Due to their widespread use, clofibric acid （CA） and carbamazepine （CBZ） have been frequently detected simultaneously at relatively high concentrations in aquatic environments. In this study, agricultural waste rice straw was employed as a potentially low-cost, effective and easy-to-operate biosorbent （RSB） to remove CA and CBZ. The adsorption of both pharmaceuticals followed pseudo second-order kinetics, and intraparticle diffusion was an important rate-limiting step. The adsorption isotherms of both drugs were fit well with Freundlich model. The adsorption of CA onto RSB was exothermic and was more likely to be dominated by physical processes, while the adsorption of CBZ was endothermic. Solution pH was determined to be the most important factor for CA adsorption, such that the adsorption capacity of CA onto RSB increased with the decline of solution pH. In the lower range of solution pH below 3. l, the CA removal efficiency was enhanced with the increase of biosorbent dosage. The CBZ removal efficiency was enhanced with the increase of RSB dosage without pH control. The maximum adsorption capacities were 126.3 mg/g for CA and 40.0 mg/g for CBZ.

Removal of clofibric acid from aqueous solution by polyethylenimine-modified chitosan beads

Polyethylenimine （PEI）-modified chitosan was prepared and used to remove clofibric acid （CA） from aqueous solution. PEI was chemically grafted on the porous chitosan through a crosslinking reaction, and the effects of PEI concentration and reaction time in the preparation on the adsorption of clofibric acid were optimized. Scanning electron microscopy （SEM） showed that PEI macromolecules were uniformly grafted on the porous chitosan, and the analysis of pore size distribution indicated that more mesopores were formed due to the crosslinking of PEI molecules in the macropores of chitosan. The PEI-modified chitosan had fast adsorption for CA within the initial 5 h, while this adsorbent exhibited an adsorption capacity of 349 mg· g^-1 for CA at pH 5.0 according to the Langmuir fitting, higher than 213 mg· g^-1 on the porous chitosan. The CA adsorption on the PEI- modified chitosan was pH-dependent, and the maximum adsorption was achieved at pH 4.0. Based on the surface charge analysis and comparison of different pharmaceu- ticals adsorption, electrostatic interaction dominated the sorption of CA on the PEI-modified chitosan. The PEI- modified chitosan has a potential application for the removal of some anionic rnicropollutants from water or wastewater.

Identification and ecotoxicity assessment of intermediates generated during the degradation of clofibric acid by advanced oxidation processes

The aim of this study was to identify the intermediates in clofibric acid degradation under various advanced oxidation processes, namely ultraviolet （UV）, UV/H2O2, vacuum ultraviolet （VUV）, VUV/H2O2, and solar/TiO2 processes, as well as to assess the toxicity of these intermediates. Eleven intermediates have been detected by gas chromatography-mass spectrometer, most of which were reported for the first time to our best knowledge. Combining the evolution of the dissolved organic carbon, CF and specific ultraviolet absorption at 254 nm, it could be deduced that cleavage of aromatic ring followed by dechlorination was the mechanism in solar/ TiO2 process, while dechlorination happened first and accumulation of aromatic intermediates occurred in the other processes. Different transformation pathways were proposed for UV-, VUV-assisted and solar/TiO2 processes, respectively. The acute toxicity was evaluated by means of Photobacterium phosphoreurn T3 spp. bioassay. It was believed that aromatic intermediates increased the toxicity and the ring-opening pathway in solar/TiO2 process could relieve the toxicity.