Pharmacokinetics of cyadox and its main metabolites in rats, pigs, chickens, and carps following oral administration at three dosage.

Cyadox (CYA), a 1,4-dioxide quinoxaline, is a safe and effective antibacterial agent with potential use in food-producing animals. The aim of this study was to compare the pharmacokinetics of CYA (Cy0) and its main metabolites [bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12)] after oral administration at three dosages in pigs, chickens, carps, and rats. The concentration vs. time profile in plasma after single oral administration indicated that CYA was rapidly dissociated into its metabolites and showed the widest distribution in all animals, with the highest apparent volume of distribution. Cy0 and Cy6 persisted for the longest time at lower concentration. Cy1and Cy4 concentration was the highest in pig and rat plasma, while Cy1 was undetectable in chickens, and Cy4 was undetectable in carps following administration at three dosages. Different dosage of the CYX and its metabolites had no significant effect on wash-out period. This study revealed obvious species-specific differences in the kinetic behavior of CYA and its metabolites, which may be related to clinical efficacy and toxicity. Our results would facilitate the judicious use of CYA in different animals.

In vitro degradation of curcuminoids by faecal bacteria: Influence of method of addition of curcuminoids into buttermilk yoghurt.

The mode of delivery of curcuminoids in the manufacture of curcuminoid-fortified buttermilk yoghurts was investigated. Curcuminoids were added prior to the addition of yoghurt cultures as powdered curcuminoids or curcuminoids pre-dissolved in ethanol and added to buttermilk prior to or after yoghurt manufacture. Only a small portion (4.6-7.7%) of the total added curcuminoids in yoghurts (299 mg/100 g) was bioaccessible after sequential exposure to simulated gastric and intestinal fluids compared to 10.9% when curcuminoids in ethanolic buffer were delivered. The total potential curcuminoid bioavailability (i.e. bioaccessible curcuminoids + curcuminoids converted by faecal bacteria) delivered in yoghurts was 19-34%, depending on the delivery formats, compared to 37% for curcuminoids delivered in ethanolic buffer. The addition of powdered curcuminoids into buttermilk prior to yoghurt fermentation had 33% total potential bioavailability. This study demonstrated the feasibility of preparing curcuminoid-fortified yoghurt for the functional food market.

Enhanced Bioaccessibility of Curcuminoids in Buttermilk Yogurt in Comparison to Curcuminoids in Aqueous Dispersions.

Curcuminoids have low bioavailability due to low aqueous solubility. We compared the bioaccessibility of curcuminoids delivered in buttermilk yogurt to that of curcuminoid powder in an aqueous dispersion. Buttermilk containing added curcuminoids (300 mg/100 g, 0.3% w/w) was used for yogurt manufacture. We measured percentage of curcuminoids remaining in yogurts after manufacture and after exposure to simulated gastrointestinal fluids, and the in vitro bioaccessibility of the curcuminoids. Curcuminoids were stable during yogurt manufacture. At the end of in vitro digestion, approximately 11% of the curcuminoids delivered in yogurt was degraded compared to <1% for curcuminoids in an aqueous dispersion. However, curcuminoids delivered in yogurt was 15-fold more bioaccessible than curcuminoids in aqueous dispersion. The small change in yogurt properties (decrease in total lactic acid bacteria counts of <1 log and increased viscosity) on addition of curcuminoids has to be balanced against the benefits of increased bioaccessibility of curcuminoids when delivered in yogurts.

Bioaccessibility of curcuminoids in buttermilk in simulated gastrointestinal digestion models.

In vitro gastrointestinal digestion models were used to investigate bioaccessibility of curcuminoids delivered with buttermilk. The percentage of solubilised curcuminoids that partitioned into the micelle in aqueous phase was determined. In fasted states (0-2.5 mg bile extract/mL sample), the bioaccessibility of curcuminoids (2% v/v ethanol) ranged from 16.3% to 26.7% in buttermilk, and from 11.4% to 18.7% with neat curcuminoids. In fed states (10-40 mg bile extract/mL sample), the bioaccessibility of curcuminoids in buttermilk was 21.3% (no ethanol) and ranged from 37.1% to 69.2% (2% v/v ethanol), while for neat curcuminoids bioaccessibility was 14.1% (no ethanol), ranging from 45.6% to 79.6% (2% v/v ethanol). The in vitro bioaccessibility of curcuminoids was influenced by the presence of the carrier (buttermilk) and ethanol, and increased significantly with increasing amount of bile extract. Curcuminoids did not markedly influence the digestibility of protein or lipids. These findings demonstrated that buttermilk could be used as a carrier for curcuminoids especially if delivered with food.

Interactions of buttermilk with curcuminoids.

The ability of buttermilk to carry and stabilise a preparation of curcuminoids was examined. The quenching of intrinsic protein fluorescence confirmed that the curcuminoids interacted with proteins in buttermilk. The Stern-Volmer quenching constant was ≥ 9.4 × 10³ M⁻¹. The apparent binding constant of curcuminoids to whole buttermilk was ≥ 2.2 × 104 M⁻¹. Centrifugation of buttermilk (5% total solids, TS)--curcuminoid mixtures demonstrated that curcuminoids were partitioned into the cream (18.0%w/w, 0.64% TS), milk serum (73.3%w/w, 2.86% TS) and the casein-rich precipitate (6.76% w/w, 1.87% TS) fractions in the ratio of 1:3.7:3.5. The interaction of curcuminoids with components in the buttermilk improved its stability, as evidenced by the faster degradation of curcuminoids in phosphate buffer (pH=6.8) than in buttermilk. The ability of buttermilk to carry and stabilise curcuminoids has the potential to enable the delivery of these components into functional foods.

Determination of total choline by liquid chromatography-electrospray ionization-tandem mass spectrometry in infant formulas.

Choline is a water-soluble nutrient important for infants' brain and neural development. In infant formulas, choline is one of the important fortified nutrients. A single-laboratory validation study conducted an LC-electrospray ionization-MS/MS to determine total choline in infant formulas. Sample preparation was adopted from AOAC Official Method 999.14, and instrumental running conditions were optimized. The LOQ was 0.2 microg/100 g, which is significant for measuring total choline in infant formulas. Average recoveries for milk-, rice-, soybean-, and hydrolyzed protein-based samples ranged from 86.45 +/- 6.04% to 108.98 +/- 3.68%, with RSD less than 7%. The repeatability RSD (RSD(r)) range was 0.24-3.59% in within-day evaluation and 1.16-3.24% in day-to-day evaluation. Matrix effect was also investigated, and can be effectively eliminated by using an internal standard. Therefore, this method has high credibility, and could be used as a routine method of quality control, or for clinical studies and other research areas.