Influence of the oral administration of excess copper on the immune response

Pocino, M; Baute, L.; Malavé, Inés

doi:10.1016/0272-0590(91)90109-h

Cited by 34 publications

(10 citation statements)

References 30 publications

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“…5). Excessive Cu intake results in impairment of both cellular and humoral immune responses [53]. Recently, Cu (II) chloride causes apoptosis of splenocytes and thymocytes, especially CD4 + T cell death [54, 55].…”

Section: Resultsmentioning

confidence: 99%

Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles

Lee

Park

et al. 2016

Part Fibre Toxicol

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BackgroundCopper nanoparticles (Cu NPs) have great potential in electronics and biomedical fields because of their efficient thermodynamic and anti-microbial properties. However, their potential toxic effects and kinetic data following repeated exposure are still unclear.MethodsWe evaluated the physicochemical properties of Cu NPs (25 nm) and copper microparticles (Cu MPs, 14–25 μm). Comparative in vivo toxicity of Cu NPs and Cu MPs was evaluated by conducting a 28-day repeated oral dose study at equivalent dose levels of 0, 100, 200, and 400 mg/kg/day (vehicle, 1 % hydroxypropyl methylcellulose). We determined Cu levels in the blood, tissues, urine, and feces by using inductively coupled plasma mass spectrometry.ResultsThe solubility of Cu NPs and Cu MPs was 84.5 and 17.2 %, respectively, in an acidic milieu; however, they scarcely dissolved in vehicle or intestinal milieus. The specific surface area of Cu NPs and Cu MPs was determined to be 14.7 and 0.16 m2/g, respectively. Cu NPs exhibited a dose-dependent increase of Cu content in the blood and tested organs, with particularly high levels of Cu in the liver, kidney, and spleen. Only for liver and kidney increased Cu levels were found in Cu MPs-treated rats. Cu NPs caused a dose-related increase in Cu levels in urine, whereas Cu MPs did not affect the urine Cu levels. Extremely high levels of Cu were detected in the feces of Cu MPs-treated rats, whereas much lower levels were detected in the feces of Cu NPs-treated rats. A comparative in vivo toxicity study showed that Cu NPs caused damages to red blood cells, thymus, spleen, liver, and kidney at ≥200 mg/kg/days, but Cu MPs did not cause any adverse effects even at the highest dose.ConclusionsOverall, the in vivo repeated dose toxicity study of Cu NPs and Cu MPs demonstrated that large surface area and high solubility in physiological milieus could directly influence the toxicological responses and biodistribution of Cu particles when administered orally. Under these experimental conditions, the no-observed-adverse-effect levels of Cu NPs and Cu MPs were determined to be 100 and ≥400 mg/kg/day, respectively.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0169-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles

Lee

Park

et al. 2016

Part Fibre Toxicol

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“…On the basis of reports that the immune response and immune cell counts can be perturbed by either high or low levels of serum Cu (Kelley et al, 1995; Pocino et al, 1991), we sought to determine if administration of QBP or 8HQ had any observable effects on immune cell types in the serum. We dosed mice intraperitoneally daily with QBP, 8HQ, or a DMSO control over the course of 2 weeks, after which complete blood counts revealed that there was no significant change in various cell types (lymphocytes, monocytes, eosinophils, and basophils) (Figure S6).…”

Section: Resultsmentioning

confidence: 99%

Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection

Festa

Helsel

Franz

et al. 2014

Chemistry & Biology

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SUMMARY Recalcitrant microbial infections demand new therapeutic options. Here we present an approach that exploits two prongs of the host immune cell antimicrobial response: the oxidative burst and the compartmentalization of copper (Cu) within phagolysosomes. The prochelator QBP is a nontoxic protected form of 8-hydroxyquinoline (8HQ) in which a pinanediol boronic ester blocks metal ion coordination by 8HQ. QBP is deprotected via reactive oxygen species produced by activated macrophages, creating 8HQ and eliciting Cu-dependent killing of the fungal pathogen Cryptococcus neoformans in vitro and in mouse pulmonary infection. 8HQ ionophoric activity increases intracellular Cu, overwhelming the Cu-resistance mechanisms of C. neoformans to elicit fungal killing. The Cu-dependent antimicrobial activity of 8HQ against a spectrum of microbial pathogens suggests that this strategy may have broad utility. The conditional activation of Cu ionophores by innate immune cells intensifies the hostile antimicrobial environment and represents a promising approach to combat infectious disease.

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“…Although much of the research that assesses copper's effect on immune function has been conducted from the perspective of Cu deficiency (Davis et al, 1987;Arthington et al, 1995;Ward et al, 1997), very little work has been done to determine the effects on immune responses during excess Cu administration. In an experiment conducted with mice, lymphoctye proliferation in response to concanavalin A was suppressed when mice were fed excess Cu, but was increased in response to Escherichia coli lipopolysaccharide stimulation (Pocino et al, 1991). In addition, Ward et al (1997) reported a decrease in lymphocyte proliferation when cattle lymphocytes were administered Cu in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…This modification is accomplished by the ability of MOS to attach to mannose binding proteins on the cell surface of some strains of bacteria, thereby preventing these bacteria from colonizing the intestinal tract by interfering with the binding of carbohydrate residues on epithelial cell surfaces (Spring et al, 2000). Also, both Cu and MOS have been reported to alter lymphocyte response in vitro (Muchmore et al, 1990;Pocino et al, 1991).…”

mentioning

confidence: 99%

Effect of dietary mannan oligosaccharides and(or) pharmacological additions of copper sulfate on growth performance and immunocompetence of weanling and growing/finishing pigs

Davis

Maxwell

Brown

et al. 2002

Journal of Animal Science

111

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Two experiments were conducted to determine the efficacy of mannan oligosaccharides (MOS) fed at two levels of Cu on growth and feed efficiency of weanling and growing-finishing pigs, as well as the effect on the immunocompetence of weanling pigs. In Exp. 1, 216 barrows (6 kg of BW and 18 d of age) were penned in groups of six (9 pens/treatment). Dietary treatments were arranged as a 2 x 2 factorial consisting of two levels of Cu (basal level or 175 ppm supplemental Cu) with and without MOS (0.2%). Diets were fed from d 0 to 38 after weaning. Blood samples were obtained to determine lymphocyte proliferation in vitro. From d 0 to 10, ADG, ADFI, and gain:feed (G:F) increased when MOS was added to diets containing the basal level of Cu, but decreased when MOS was added to diets containing 175 ppm supplemental Cu (interaction, P < 0.01, P < 0.10, and P < 0.05, respectively). Pigs fed diets containing 175 ppm Cu from d 10 to 24 and d 24 to 38 had greater (P < 0.05) ADG and ADFI than those fed the basal level of Cu regardless of MOS addition. Pigs fed diets containing MOS from d 24 to 38 had greater ADG (P < 0.05) and G:F (P < 0.10) than those fed diets devoid of MOS. Lymphocyte proliferation was not altered by dietary treatment. In Exp. 2, 144 pigs were divided into six pigs/pen (six pens/treatment). Dietary treatments were fed throughout the starter (20 to 32 kg BW), grower (32 to 68 kg BW), and finisher (68 to 106 kg BW) phases. Diets consisted of two levels of Cu (basal level or basal diet + 175 ppm in starter and grower diets and 125 ppm in finisher diets) with and without MOS (0.2% in starter, 0.1% in grower, and 0.05% in finisher). Pigs fed supplemental Cu had greater (P < 0.05) ADG and G:F during the starter and grower phases compared to pigs fed the basal level of Cu. During the finisher phase, ADG increased when pigs were fed MOS in diets containing the basal level of Cu, but decreased when MOS was added to diets supplemented with 125 ppm Cu (interaction, P < 0.05). Results from this study indicate the response of weanling pigs fed MOS in phase 1 varied with level of dietary Cu. However, in phase 2 and phase 3, diets containing either MOS or 175 ppm Cu resulted in improved performance. Pharmacological Cu addition improved gain and efficiency during the starter and grower phases in growing-finishing pigs, while ADG response to the addition of MOS during the finisher phase seems to be dependent upon the level of Cu supplementation.

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Influence of the oral administration of excess copper on the immune response

Cited by 34 publications

References 30 publications

Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles

Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles

Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection

Effect of dietary mannan oligosaccharides and(or) pharmacological additions of copper sulfate on growth performance and immunocompetence of weanling and growing/finishing pigs

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