Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice.

Natural astaxanthin is the strongest antioxidant ever discovered, with many biological functions, and it is widely used in the fields of health food and biomedical research. In the present study, we aimed to investigate the plasma concentration, distribution and safety of astaxanthin from Haematococcus pluvialis in pregnant mice. In the acute studies, the oral LD50 of astaxanthin was greater than 20 g/kg·bw. In mouse bone marrow micronucleus test, 10 g/kg·bw astaxanthin did not cause damage to chromosomes and mitotic apparatus of pregnant mice. After treatment with a single dose of 500 mg/kg·bw astaxanthin, the concentration of astaxanthin in plasma reached the maximum at 8 h (55.7 µg/L), which was completely metabolized after 48 h. In the repeat-dose toxicity test, 100, 250 and 500 mg/kg·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.

Water-dispersible astaxanthin-rich nanopowder: preparation, oral safety and antioxidant activity in vivo.

In this research, astaxanthin-rich nanopowder was prepared by nanoencapsulation and freeze-drying techniques with enhanced bioavailability and antioxidant activities. The nanopowder showed a maximum solubility of 230 mg mL-1 with an astaxanthin content as high as 2.9%. Compared with free astaxanthin, the astaxanthin-loaded nanopowder exhibited a more efficient antioxidant effect: an oral dose of 0.9 mg per kg BW significantly reduced the malondialdehyde and protein carbonyl contents, and increased the glutathione content as well as the superoxide dismutase activities in alcohol-induced acute hepatic injured mice, and maintained these oxidative stress indicators at a normal level for a longer period when treated with nanoencapsulated-astaxanthin than free astaxanthin. Simulated gastrointestinal tract studies demonstrated that the nanopowder with pH and DNase I-dependent dissociation properties delivered astaxanthin efficiently to the small intestine. Astaxanthin-rich nanopowder with a dose as high as 2.4 mg per kg BW (equivalent to astaxanthin) showed no chronic toxicity to mice in terms of hematology and pathological histology, indicating its impressive biocompatibility for biomedical applications. Pharmacokinetics and relative bioavailability (207%) of the nanopowder further proved that DNA/chitosan nanocarriers significantly improved the delivery efficiency of astaxanthin. With enhanced bioavailability and antioxidant activities, this novel type of astaxanthin-loaded nanopowder is expected to find broad application in the food and drug industry.

Assessment of tissue distribution and concentration of ß-cryptoxanthin in response to varying amounts of dietary ß-cryptoxanthin in the Mongolian gerbil.

There is a general lack of knowledge regarding the absorption and tissue storage of the provitamin A carotenoid ß-cryptoxanthin. The present study investigated the whole-body tissue distribution of ß-cryptoxanthin in an appropriate small animal model, the Mongolian gerbil (Meriones unguiculatus), for human provitamin A carotenoid metabolism. After 5 d of carotenoid depletion, five gerbils were euthanised for baseline measurements. The remaining gerbils were placed in three weight-matched treatment groups (n 8). All the groups received 20 µg/d of ß-cryptoxanthin from tangerine concentrate, while the second and third groups received an additional 20 and 40 µg/d of pure ß-cryptoxanthin (CX40 and CX60), respectively, for 21 d. During the last 2 d of the study, urine and faecal samples of two gerbils from each treatment group were collected. ß-Cryptoxanthin was detected in the whole blood, and in twelve of the fourteen tissues analysed. Most tissues resembled the liver, in which the concentrations of ß-cryptoxanthin were significantly higher in the CX60 (17·8 (sem 0·7) µg/organ; P= 0·004) and CX40 (16·2 (sem 0·9) µg/organ; P= 0·006) groups than in the CX20 group (13·3 (sem 0·4) µg/organ). However, in intestinal tissues, the concentrations of ß-cryptoxanthin increased only in the CX60 group. Despite elevated vitamin A concentrations in tissues at baseline due to pre-study diets containing high levels of vitamin A, ß-cryptoxanthin maintained those vitamin A stores. These results indicate that ß-cryptoxanthin is stored in many tissues, potentially suggesting that its functions are widespread.

Beta-cryptoxanthin from citrus juices: assessment of bioaccessibility using an in vitro digestion/Caco-2 cell culture model.

Beta-Cryptoxanthin (beta-CX), a provitaminic carotenoid of potential interest for health, is found principally in Citrus fruit in both free and esterified forms. Little is known about the intestinal absorption of beta-CX especially with regard to the esterified forms. The aim of this study was to evaluate the absorption of free and esterified beta-CX using simulated digestion coupled with the Caco-2 model. Bioaccessibility was investigated by measuring the transfer of carotenoids from different citrus juices into micelles using an in vitro digestion system. Then, carotenoid uptake was evaluated by adding carotenoid-rich micelles (from the in vitro digestion) or synthetic micelles (made from synthetic lipids and carotenoids purified from citrus juice) to human intestinal cells (Caco-2 TC7 clone). Our results showed that beta-cryptoxanthin esters (beta-CXE) were partially hydrolysed during the in vitro digestion. The bioaccessibility of free beta-CX measured was significantly higher (40 (SD 1.05) %) than that of beta-carotene (30 (SD 1.9) %) and beta-CXE (16 (SD 1.5) %). In the same way, the incorporation of free beta-CX (27 (SD 1.01) %) into synthetic micelles exceeded (P<0.05) that of beta-carotene (10 (SD 0.7) %) and beta-CXE (8.8 (SD 0.4) %). In the case of micelles from in vitro digestion, the uptake of beta-carotene, free beta-CX and beta-CXE forms by Caco-2 cells was 14.3 (SD 1.8), 3.9 (SD 1.3), and 0.7 (SD 0.08) % respectively. These results showed a preferential uptake by Caco-2 cells of beta-carotene and free beta-CX compared with the two esters of beta-CX.