Differential effect of nanoparticle and standard forms of ZnO on serum zinc and magnesium levels in rats.

This study examined the effect of chronic (2 weeks) administration of zinc oxide nanoparticles (NPs-ZnO) and standard zinc oxide (S-ZnO) on the levels of zinc (Zn), magnesium (Mg) and calcium (Ca) in rat serum. S-ZnO and NPs-ZnO were administered either per os (p.o.) or intraperitoneally (i.p.) at doses of 7 mg/kg or 14 mg/kg. Neither form of ZnO administered p.o. altered serum zinc concentration. However, different effects dependent upon either S-ZnO or NPs-ZnO forms were noticed after i.p. administration. Namely, while S-ZnO increased serum zinc concentration (by 136%) only at the higher dose (14 mg/kg), both doses of NPs-ZnO increased zinc concentration (by 97% at 7 mg/kg and by 564% at 14 mg/kg). The form-dependence of the ZnO effect was also demonstrated in the effect on the serum magnesium level. Only the S-ZnO form (at the dose of 14 mg/kg) reduced serum magnesium concentration (by 14% p.o., 6% i.p.). No influence of NPs-ZnO on the serum calcium level was observed. The present study demonstrated effects on the serum Zn and Mg levels, which differed between the standard and nanoparticle forms of ZnO. This may contribute to the different functional effects of these ZnO forms shown previously.

Beneficial effect of nanoparticles over standard form of zinc oxide in enhancing the anti-inflammatory activity of ketoprofen in rats.

BACKGROUND: Zinc is known as an anti-inflammatory agent. Recent studies demonstrated the usage of zinc ions for enhancing the anti-inflammatory effect of Non-Steroidal Anti-inflammatory Drugs (NSAIDs). METHODS: This study compares the influence of chronic administration of zinc oxide nanoparticles (ZnO-NPs) and zinc oxide standard form (ZnO-S) on the anti-inflammatory and gastric activity of ketoprofen in rats. Both ZnO-S and ZnO-NPs were administered at doses of 7 or 14mg/kg (intraperitoneally (ip) and per os (po)) for 2 weeks followed by single po ketoprofen administration (in three doses: 5, 10, and 20mg/kg). RESULTS: The ZnO-NPs (but not ZnO-S) at a dose of 14mg/kg ip reduced the carrageenan-induced paw edema at the second hour after carrageenan administration and enhanced the ketoprofen anti-inflammatory activity at second and third hour after carrageenan administration. A dose of 7mg/kg of both forms administered ip was ineffective in these measures. ZnO-NPs and ZnO-S administered po did not affect the carrageenan-induced paw edema or ketoprofen anti-inflammatory activity. ZnO-S and ZnO-NPs administered po and ip at both doses (7 and 14mg/kg) protected the gastric mucosa from ketoprofen-induced gastric ulcer. CONCLUSION: Zinc oxide nanoparticles demonstrated beneficial effects over standard form in enhancing the anti-inflammatory activity of ketoprofen.

Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling.

Zinc is a nutritionally fundamental trace element, essential to the structure and function of numerous macromolecules, including enzymes regulating cellular processes and cellular signaling pathways. The mineral modulates immune response and exhibits antioxidant and anti-inflammatory activity. Zinc retards oxidative processes on a long-term basis by inducing the expression of metallothioneins. These metal-binding cysteine-rich proteins are responsible for maintaining zinc-related cell homeostasis and act as potent electrophilic scavengers and cytoprotective agents. Furthermore, zinc increases the activation of antioxidant proteins and enzymes, such as glutathione and catalase. On the other hand, zinc exerts its antioxidant effect via two acute mechanisms, one of which is the stabilization of protein sulfhydryls against oxidation. The second mechanism consists in antagonizing transition metal-catalyzed reactions. Zinc can exchange redox active metals, such as copper and iron, in certain binding sites and attenuate cellular site-specific oxidative injury. Studies have demonstrated that physiological reconstitution of zinc restrains immune activation, whereas zinc deficiency, in the setting of severe infection, provokes a systemic increase in NF-κB activation. In vitro studies have shown that zinc decreases NF-κB activation and its target genes, such as TNF-α and IL-1ß, and increases the gene expression of A20 and PPAR-α, the two zinc finger proteins with anti-inflammatory properties. Alternative NF-κB inhibitory mechanism is initiated by the inhibition of cyclic nucleotide phosphodiesterase, whereas another presumed mechanism consists in inhibition of IκB kinase in response to infection by zinc ions that have been imported into cells by ZIP8.

Does titanium in ionic form display a tissue-specific distribution?

Most studies have focused on the biodistribution of titanium(IV) oxide as nanoparticles or crystals in organism. But several reports suggested that titanium is released from implant in ionic form. Therefore, gaining insight into toxicokinetics of Ti ions will give valuable information, which may be useful when assessing the health risks of long-term exposure to titanium alloy implants in patients. A micro synchrotron radiation-induced X-ray fluorescence (µ-SRXRF) was utilized to investigate the titanium distribution in the liver, spleen and kidneys of rats following single intravenous or 30-days oral administration of metal (6 mg Ti/b.w.) in ionic form. Titanium was mainly retained in kidneys after both intravenous and oral dosing, and also its compartmentalization in this organ was observed. Titanium in the liver was non-uniformly distributed-metal accumulated in single aggregates, and some of them were also enriched in calcium. Correlation analysis showed that metal did not displace essential elements, and in liver titanium strongly correlated with calcium. Two-dimensional maps of Ti distribution show that the location of the element is characteristic for the route of administration and time of exposure. We demonstrated that µ-SRXRF can provide information on the distribution of titanium in internal structures of whole organs, which helps in enhancing our understanding of the mechanism of ionic titanium accumulation in the body. This is significant due to the popularity of titanium implants and the potential release of metal ions from them to the organism.

Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.

Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients.