Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function.

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in "a regular non-ketogenic diet" is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1.

Serum Metabonomics of Mild Acute Pancreatitis.

BACKGROUND: Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. METHODS: An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. RESULTS: A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P < 0.05). CONCLUSION: Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course.

A simple RP-HPLC method for the simultaneous determination of curcumin and its prodrug, curcumin didecanoate, in rat plasma and the application to pharmacokinetic study.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of curcumin and its prodrug, curcumin didecanoate (CurDD), in rat plasma. The analytes were extracted by ethyl acetate following the addition of sodium dodecyl sulfate, and separated on a reverse-phase C(18) column using a gradient mobile phase system of acetonitrile-tetrahydrofuran-water containing 0.1% formic acid. Detection by UV absorption at 425 nm gave a lower limit of quantitation (LLOQ) of 5 and 10 ng/mL for curcumin and CurDD in 50 µL of plasma, respectively. Intra- and inter-day precisions of quality control samples except those at LLOQ were within 15% for curcumin and CurDD, respectively, and the accuracies for both compounds were between 93.9 and 108%. The method was successfully applied to determine plasma concentration-time curves of curcumin and CurDD in rats following intravenous (i.v.) administration of curcumin or CurDD at doses of 1 mg/kg (calculated as curcumin). The results suggested that i.v. dosed CurDD provided sustained plasma levels of curcumin.

Causes of reduced survival of neonatal pigs by medium-chain triglycerides: blood metabolite and behavioral activity approaches.

Two experiments were conducted to investigate the causes of the failure of orally dosed medium-chain triglycerides (MCT) in improving the survival of neonatal pigs. In Exp. 1, four litters consisting of 24 unsuckled neonatal pigs were either dosed with 6 mL/kg BW.75 of MCT or the dosing process was mimicked by inserting and withdrawing the feeding tube at 10 and 18 h after birth. Blood beta-hydroxybutyrate concentration was increased (P < .06) and the depletion of liver glycogen was reduced (P < .05) by MCT. Plasma octanoate (C8) concentration peaked at 1 h and was minimized at 4 to 8 h after each MCT dosage; decanoate (C10) concentration increased (P < .001) gradually after each dosage. Activity of pigs was decreased (P < .01) by MCT. In Exp. 2, 94 litters consisting of 887 neonatal pigs were dosed with either 6 mL/kg BW.75 of MCT, coconut oil (CO), or saline at 10 to 14 and 20 to 28 h after birth. Milk intake (P < .05) and weight gain were reduced (P < .01) in 1- to 2-d-old pigs dosed with MCT compared with intake and gain of pigs dosed with saline. Mortality of large pigs (> 1 kg) was increased (P < .05) but mortality of small pigs (< 1 kg) was not affected by MCT. Mortality of small pigs was reduced (P < .05) but mortality of large pigs (> 1 kg) was not affected by CO. Standing, walking, and suckling behaviors of pigs were not affected by MCT or CO. Coma was evident in 9.7% of pigs dosed with MCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Production and disposal of medium-chain fatty acids in children with medium-chain acyl-CoA dehydrogenase deficiency.

The effect of fasting on plasma concentrations of fatty acids has been determined in four children with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In addition, the in vivo rate of octanoate oxidation was measured, using [1-13C]octanoate. In the three older children (1.5-11.2 years), fasting for up to 18 h stimulated lipolysis, as reflected by the increasing concentration of free fatty acids, but with little rise in concentrations of medium-chain fatty acids, octanoate, decanoate and cis-4-decenoate. In an infant (0.5 year), lipolysis was greater and was accompanied by rising concentrations of medium-chain fatty acids. After 13.5 h there was a rapid increase in the concentration of decanoate and cis-4-decenoate. The calculated in vivo rate of octanoate oxidation was substantial in all patients studied (6.4-13.1 mumol/kg per h) despite very low MCAD activity in vitro. It is concluded that under basal conditions the in vivo oxidation rate of medium-chain fatty acids is near normal in the four children studied with MCAD deficiency.

Utilization of medium-chain triglycerides by neonatal pigs: effects of emulsification and dose delivered.

Four trials were conducted using 86, 24-h-old pigs to evaluate the utilization of medium-chain triglycerides (MCT). Effects of emulsification and amount of MCT fed were examined. After a 4-h period during which feed was withheld, pigs were force-fed MCT (containing 75% octanoate and 25% decanoate), marking time 0 of the experiment. Blood samples were obtained at 1 and 2 h for subsequent medium-chain fatty acid (MCFA) analysis. In Trials 1 (six pigs/treatment) and 2 (four pigs/treatment) the response to three emulsifying agents was compared to a nonemulsified (NE) control. Twenty milliliters of a 30% (vol/vol) emulsion of MCT or 6 mL of NE MCT was administered. Concentrations of MCFA at 1 h in pigs receiving a Tween 80 (polyoxy-ethylene [20] sorbitan monooleate) emulsion were 3- to 19-fold higher than concentrations in animals administered a gum arabic/gum tragacanth emulsion, a lecithin emulsion, or NE MCT. Trials 3 (eight pigs/treatment) and 4 (six pigs/treatment) were conducted to determine the plasma MCFA concentrations resulting from feeding increasing levels of NE (3, 6, 9, or 12 mL of MCT) or emulsified MCT oil (2, 4, 6, or 8 mL in a 30% Tween 80 emulsion). Plasma octanoate concentrations measured at 1 h increased linearly (P < .05) with increasing MCT dosage through 9 mL of NE and 6 mL of emulsified MCT. A transient narcosis was observed in 8 of 12 animals that received 6 or 8 mL of emulsified MCT and was most pronounced 1 to 2 h after feeding, which roughly corresponded to peak plasma MCFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)