Comparative distribution of beta-carotene and lycopene after intraperitoneal administration in mice.

To determine the kinetics of accumulation of beta-carotene and lycopene, and their main storage sites, they were separately administered in OFI mice at a single dose of 10 mg/kg body weight or in combination. Animals were sacrificed at given time intervals after intraperitoneal administration and carotenoids were dosed in serum, liver, spleen, kidneys and lungs. A single injection of beta-carotene led to a serum peak at t = 2 h and high levels were detected in the liver after 0.75 hours and in the spleen after 5 hours, with peak values of 10.46 +/- 0.62 and 134 +/- 6 micrograms/g tissue respectively. In contrast, lungs and kidneys did not appear as main accumulation sites. After administration of the carotenoid association, beta-carotene distribution in the four organs was strongly inhibited by lycopene. Concerning lycopene distribution, the concentration values were lower than beta-carotene, the spleen and liver remaining the main storage sites. After administration of a combined dose carotene/lycopene, the percentage of lycopene distribution inhibition was lower compared to the beta-carotene distribution inhibition induced by lycopene. This unusual and non-physiological way of administration for micronutrients leads to high levels of beta-carotene and lycopene in the liver and spleen, and seems of interest in the experimental study and understanding of the biomolecular mechanisms of their activities when administered alone or together.

In vitro comparative study of cytolysis mediated by natural killer cells towards malignant cells preincubated with antioxidants.

We have previously reported that antioxidants such as beta-carotene, were able to enhance cytolytic activity of NK cells. The aim of the present study was to investigate whether preincubating YAC-1 tumor cells in culture with different antioxidants, affected their NK cell-mediated cytolysis. The antioxidants studied were enzymes (superoxide dismutase and catalase), hydroxyl radical scavengers (thiourea, mannitol, dimethyl sulfoxide) and a singlet oxygen quencher: beta-carotene. After 24 hours coincubation with the antioxidants, radiolabeled YAC-1 cells were submitted to the cytotoxic activity of NK cells for a 4 hour period. For some antioxidants, a moderate increase of cytotoxic potential occurred for weak NK cell number. By contrast, a clear decrease of cytotoxic potential was induced with high NK cell number. An antioxidant, with a protective effect which appeared stronger was thiourea, which induced 20, 58 and 36% decrease of cytolysis in the effector-target ratios 50:1, 100:1 and 200:1 respectively. These studies suggest that the malignant YAC-1 cells are vulnerable to treatment by different antioxidants.

Modulation of natural killer cell functional activity in athymic mice by beta-carotene, oestrone and their association.

In athymic mice, Natural Killer (NK) cells influence the take rate and growth of human malignant tissue xenografts. To confirm preliminary results, comparative experiments were conducted to study the effects of beta-carotene, oestrone and their association on the cytolysis mediated by spleen NK cells from athymic mice receiving these different treatments. Target cells consisted of YAC-1 malignant cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta-carotene induced a significant activation of NK cells (p < 0.002). This effect could be attributed to its antioxidant properties and confirmed by a moderate increase in erythrocyte glutathione peroxidase activity. On the contrary, oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this case, the prooxidant properties of oestrone could explain its effect on NK cells and agree with the increase of intracellular reduced glutathione level observed. When mice received the combination beta-carotene-oestrone, their opposite effects on NK cell activity were counterbalanced, leading to a moderate change of cytolysis.