Zinc induces chemokine and inflammatory cytokine release from human promonocytes.

Our previous studies found that zinc oxide (ZnO) particles induced expression of intercellular adhesion molecule-1 (ICAM-1) protein in vascular endothelial cells via NF-κB and that zinc ions dissolved from ZnO particles might play the major role in the process. This study aimed to determine if zinc ions could cause inflammatory responses in a human promonocytic leukemia cell line HL-CZ. Conditioned media from the zinc-treated HL-CZ cells induced ICAM-1 protein expression in human umbilical vein endothelial cells (HUVEC). Zinc treatment induced chemokine and inflammatory cytokine release from HL-CZ cells. Inhibition of NFκB activity by over-expression of IκBα in HL-CZ cells did not block the conditioned medium-induced ICAM-1 protein expression in HUVEC cells. Zinc treatment induced activation of multiple immune response-related transcription factors in HL-CZ cells. These results clearly show that zinc ions induce chemokine and inflammatory cytokine release from human promonocytes, accompanied with activation of multiple immune response-related transcription factors. Our in vitro evidence in the zinc-induced inflammatory responses of vascular cells provides a critical linkage between zinc exposure and pathogenesis of those inflammatory vascular diseases.

Comparative in vitro toxicity of seven zinc-salts towards neuronal PC12 cells.

Currently much attention has been given to the neurotoxicity of zinc, yet little is known about the influence of the counterions present. Therefore, we investigated the influence of different Zn(2+)-salts (concentrations range 0.05-0.3 mM) on cell viability, ATP and glutathione concentration and caspase activation in differentiated PC12 cells as a model for neuronal cells. Generally, at concentrations of 0.05 mM most Zn(2+)-salts were not cytotoxic except for zinc-citrate. At concentrations between 0.1 and 0.3 mM Zn(2+) a significant decrease in GSH and ATP levels preceded cell death induced by all salts, except of zinc-histidinate. Zinc-citrate and zinc-sulphate turned out to be the most toxic salts particularly at low concentrations. Analyses of caspase 3/7 activity showed that dependent on the concentration and the type of the salt used cell death may show more or less signs of both, necrosis and apoptosis. Interestingly, the uptake of Zn(2+) from zinc-sulphate and zinc-citrate was significantly higher than that of other salts, implicating a correlation between uptake and toxicity. In conclusion, Zn(2+)-salts could be divided into three categories with high (zinc-citrate, zinc-sulphate), moderate (zinc-orotate, zinc-acetate, zinc-chloride(,) zinc-gluconate) and low cytotoxicity (zinc-histidinate).

Differential effects of lead and zinc on inhibitory avoidance learning in mice

We studied the effects of chronic intoxication with the heavy metals lead (Pb2+) and zinc (Zn2+) on memory formation in mice. Animals were intoxicated through drinking water during the pre- and postnatal periods and then tested in the step-through inhibitory avoidance memory task. Chronic postnatal intoxication with Pb2+ did not change the step-through latency values recorded during the 4 weeks of the test (ANOVA, P>0.05). In contrast, mice intoxicated during the prenatal period showed significantly reduced latency values when compared to the control group (day 1: q = 4.62, P<0.05; day 7: q = 4.42, P<0.05; day 14: q = 5.65, P<0.05; day 21: q = 3.96, P<0.05, and day 28: q = 6.09, P<0.05). Although chronic postnatal intoxication with Zn2+ did not alter a memory retention test performed 24 h after training, we noticed a gradual decrease in latency at subsequent 4-week intervals (F = 3.07, P<0.05), an effect that was not observed in the control or in the Pb2+-treated groups. These results suggest an impairment of memory formation by Pb2+ when the animals are exposed during the critical period of neurogenesis, while Zn2+ appears to facilitate learning extinction