Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation.

BACKGROUND: Oxidative stress with dysregulated inflammation are hallmarks of sepsis. Zinc and selenium have important antioxidant functions, such that they could be important in patients with sepsis. We used an in vitro approach to assess the effect of zinc and selenium on oxidative stress, mitochondrial function, and inflammatory responses in conditions mimicking sepsis and related the findings to plasma concentrations and biomarkers in patients with and without sepsis. METHODS: Human endothelial cells were exposed to a range of zinc and selenium concentrations in conditions mimicking sepsis. Zinc, selenium, and a series of biomarkers of oxidative stress and inflammation were measured in plasma from critically ill patients with and without sepsis. RESULTS: Culturing cells with different concentrations of zinc caused altered zinc transporter protein expression and cellular zinc content, and selenium affected glutathione peroxidase 3 activity. Although zinc or selenium at physiological concentrations had no effect on interleukin-6 release in vitro, higher concentrations of the trace elements were associated with improved mitochondrial function. Plasma zinc and selenium concentrations were low in patients [zinc: median (range) 4.6 (2.1-6.5) µM in control patients without sepsis and 3.1 (1.5-5.4) µM in patients with sepsis, P=0.002; and selenium: 0.78 (0.19-1.32) µM in control patients and 0.42 (0.22-0.91) µM in sepsis patients, P=0.0009]. Plasma concentrations of interleukin-6, other biomarkers of inflammation, and markers of oxidative damage to proteins and lipids were elevated, particularly in patients with sepsis, and were inversely related to plasma zinc and selenium concentrations. CONCLUSIONS: Zinc and selenium concentrations were reduced in critically ill patients, with increased oxidative stress and inflammatory biomarkers, particularly in patients with sepsis. Oxidative stress as a result of suboptimal selenium and zinc concentrations might contribute to damage of key proteins. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT01328509.

Assessment of zinc and copper status in weaned piglets in relation to dietary zinc and copper supply.

The aim of the study was to determine the effect of weaning and the effect of increasing dietary zinc concentrations on the zinc and copper status of weaned piglets (study 1) and to study the effect of high concentrations of dietary zinc and/or copper on zinc and copper status of weaned piglets (study 2). Study 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was killed 1 day before weaning. The remaining 48 piglets were allocated at weaning (28 days) to four dietary zinc treatments (100, 250, 1000 or 2500 ppm) and subsequently killed 1-2, 5-6 or 14-15 days after weaning. Study 2 included 48 piglets (six litters of eight piglets) allocated to four dietary treatments, consisting of low or high dietary zinc (100 or 2500 ppm) in combination with low or high dietary copper (20 or 175 ppm). All piglets in study 2 were killed 5-7 days after weaning. In both studies, the trace mineral status was assessed by zinc and copper concentrations and alkaline phosphatase (AP) activity in plasma and mucosal tissue. In study 2, lymphocyte metallothionein (MT) mRNA and intestinal mucosa MT mRNA concentrations were included as zinc status markers. The results showed that the zinc status, measured as zinc in plasma and mucosa, was not affected by weaning of the piglets. Plasma copper concentrations decreased during the first 2 weeks after weaning. High dietary copper concentrations did not affect the concentration of copper in plasma, but increased the concentration of copper in mucosa and the concentration of zinc in plasma. The dietary zinc treatments increased the zinc concentration in plasma as well as the zinc and MT mRNA concentration in mucosa. Lymphocyte MT mRNA concentrations did not reflect the differences in dietary zinc supplementation.

Rat metallothionein-2 contains N(alpha)-acetylated and unacetylated isoforms.

Mammalian metallothioneins (MT), are characteristically N(alpha)-acetylated and the presence of an unblocked N-terminus has not previously been reported. On-line capillary electrophoresis-electrospray mass spectrometry of hepatic MT-2 from rats injected with zinc revealed two isoforms differing by a mass equivalent to that of a single acetyl group. The lower mass component constituted > 20% of total MT-2 protein and both MT-2 isoforms were separated by reversed-phase high-performance liquid chromatography. The identity of each fraction was confirmed by matrix-assisted laser desorption ionisation mass spectrometry, and amino acid analysis and N-terminal sequencing revealed that the lower mass isoform was unblocked at the N-terminus and had an amino acid composition and sequence which is characteristic of rat MT-2. Thus the complementary techniques of mass spectrometry and N-terminal sequencing demonstrated conclusively that purified MT-2 from zinc-treated rats contains an unacetylated isoform. We propose that the cotranslational acetylation of rat MT-2 may under some circumstances be inefficient compared to that in other nonrodent species, where we have detected only trace levels of unacetylated MT isoforms.

The influence of a low-boron diet and boron supplementation on bone, major mineral and sex steroid metabolism in postmenopausal women.

An increase in dietary intake of B from 0.25 to 3.25 mg/d has been reported to increase plasma oestradiol and testosterone and decrease urinary Ca excretion in postmenopausal women. Consequently, it is suggested that the higher level of B intake could reduce bone loss associated with the menopause and cessation of ovarian function. The present study was designed to investigate the effect of a B supplement on bone mineral absorption and excretion, plasma sex steroid levels and urinary excretion of pyridinium crosslink markers of bone turnover in healthy postmenopausal volunteers. The women were accommodated in a metabolic unit, given a low-B diet (LBD; 0.33 mg/d) for 3 weeks and were asked to take a B supplement of 3 mg/d in addition to the LBD for a further 3 weeks. Changing B intake from 0.33 to 3.33 mg/d had no effect on minerals, steroids or crosslinks. However, the LBD appeared to induce hyperabsorption of Ca since positive Ca balances were found in combination with elevated urinary Ca excretion. This phenomenon may have inhibited or obscured any effect of B.