Lipid peroxidative stress and antioxidative enzymes in brains of milk-supplemented rats.

Skim milk cultured with lactic acid bacteria has been previously reported to reduce lipid peroxidation in rat livers. In this study, the effects of skim milk and cultured milk supplementation on peroxidative stress in brains of weanling rats were investigated. We observed a reduction of brain thiobarbituric acid reacting substances (TBARS) concentration in milk-supplemented animals as compared with controls. In brains of control rats, the superoxide dismutase (SOD) enzyme levels were significantly higher than those from the milk-supplemented animals. In addition, SOD activity in control animal brains had a positive correlation with the TBARS concentration. There was no significant differences in the brain glutathione-S-transferase (GST) levels of all the three groups of animals. The results suggest that milk supplementation may be beneficial in reducing peroxidative stress in the developing rat brain.

Adding Zn2+ induces DNA fragmentation and cell condensation in cultured human Chang liver cells.

Zinc (Zn) is a trace element in human cells and regarded as an essential nutrient with established deficiency states affecting multiple organs in the body. However, it has been reported that Zn uptake is associated with some serious harmful effects, such as inhibition of DNA synthesis and enhanced toxicity from reactive oxygen species. We have previously shown that in vivo administration of Zn2+ in C57/6J mice induces weight loss and massive hair loss where the normal course hair becomes replaced by fine vello hair, simulating the side effects from cancer chemotherapy where oxidative free radical damage is implicated in association with DNA fragmentation and programmed cell death (PCD). Here, in vitro flow cytometric studies on human Chang liver showed Zn2+ causing cell condensation with DNA fragmentation that occurred in a dose-dependent manner, an effect replicated by micrococcal nuclease digestion. Specific terminal deoxynucleotidyl transferase-(TdT) mediated labeling of 3'-OH ends of DNA nicks corroborated the flow cytometric profiles of propidium iodide-DNA binding where degradation of both 2 and 4 N genomic DNA resulted in a solitary 1N peak presentation. DNA degradation concomitant with cell condensation is seen as an established hallmark of PCD. We further showed that Zn2+ could enhance the generation of hydroxyl free radicals (OH.) by the transition metal vanadium. Glutathione, the cell's main reducing agent, underwent corresponding reduction. The results suggested that Zn supplementation could induce features resembling PCD.

Flow cytometric evaluation of the DNA profile and cell cycle of zinc supplemented human Chang liver cells.

Zinc, an essential trace element, is important for normal cell growth. Growing children, especially at puberty, require increased zinc (2.8 mg/day for males and 2.65 mg/day for females). The DNA profile and cell cycle of human Chang liver cells grown in 0-900 mumol/L zinc chloride supplemented serum-free media for 24 h were analyzed using a Coulter flow cytometer. There was no significant difference in the G1, S and G2/M phases between zinc treated cells and control cultures except at 90 and 900 mumol/L zinc chloride. At these two higher dosages, fragmentation of genomic DNA into sub-2N DNA (sub-G1 DNA), generally considered a hallmark of programmed cell death (PCD), was noted. Results of the present study seem to suggest that growth regulation by zinc during growth spurts such as at puberty, could also be influenced by other factors besides its direct effect on DNA synthesis. In addition, high dosages of zinc could be cytotoxic.