Alterations of Bio-elements, Oxidative, and Inflammatory Status in the Zinc Deficiency Model in Rats.

Urszula Doboszewska,Joanna Gołębiowska,Paulina Misztak,Marek Lankosz,Magdalena Sowa-Kućma,Katarzyna Młyniec,Beata Ostachowicz,Mirosław Krośniak,Agnieszka Wojtanowska-Krośniak,Bernadeta Szewczyk,Wojciech Piekoszewski,Karolina Noworyta-Sokołowska,Gabriel Nowak,Krystyna Gołembiowska

doi:10.1007/s12640-015-9571-7

Abstract

Our previous study showed that dietary zinc restriction induces depression-like behavior with concomitant up-regulation of the N-methyl-d-aspartate receptor (NMDAR). Because metal ions, oxidative stress, and inflammation are involved in depression/NMDAR function, in the present study, bio-elements (zinc, copper, iron, magnesium, and calcium), oxidative (thiobarbituric acid-reactive substances; protein carbonyl content), and inflammatory (IL-1α, IL-1β) factors were measured in serum, hippocampus (Hp), and prefrontal cortex (PFC) of male Sprague–Dawley rats subjected to a zinc-adequate (ZnA) (50 mg Zn/kg) or a zinc-deficient (ZnD) (3 mg Zn/kg) diet for 4 or 6 weeks. Both periods of dietary zinc restriction reduced serum zinc and increased serum iron levels. At 4 weeks, lowered zinc level in the PFC and Hp as well as lowered iron level in the PFC of the ZnD rats was observed. At 6 weeks, however, iron level was increased in the PFC of these rats. Although at 6 weeks zinc level in the PFC did not differ between the ZnA and ZnD rats, extracellular zinc concentration after 100 mM KCl stimulation was reduced in the PFC of the ZnD rats and was accompanied by increased extracellular iron and glutamate levels (as measured by the in vivo microdialysis). The examined oxidative and inflammatory parameters were generally enhanced in the tissue of the ZnD animals. The obtained data suggest dynamic redistribution of bio-elements and enhancement of oxidative/inflammatory parameters after dietary zinc restriction, which may have a link with depression-like behavior/NMDAR function/neurodegeneration.

Highlights

IntroductionZinc is the second (after iron) most prevalent trace element in the human body. Its importance has been demonstrated in many physiological processes
Zinc is the second most prevalent trace element in the human body
Oxidative stress, and inflammation are involved in depression/N-methyl-D-aspartate receptor (NMDAR) function, in the present study, bio-elements, oxidative, and inflammatory (IL-1a, IL-1b) factors were measured in serum, hippocampus (Hp), and prefrontal cortex (PFC) of male Sprague–Dawley rats subjected to a zinc-adequate (ZnA) (50 mg Zn/kg) or a zinc-deficient (ZnD) (3 mg Zn/ kg) diet for 4 or 6 weeks

Summary

Introduction

Zinc is the second (after iron) most prevalent trace element in the human body. Its importance has been demonstrated in many physiological processes. Zinc deficiency primarily has an impact on T cells function and affects Th1 and (to a lesser extend) Th2 cytokines production (Bonaventura et al 2015). Zinc deficiency influences production of interleukin (IL)-1b by macrophages (Bonaventura et al 2015). Altered production of cytokines during zinc deficiency may lead to inflammation, e.g., zinc depletion from macrophages induces IL-1b secretion and activates NLRP3 inflammasome (Summersgill et al 2014). Zinc which is (in contrast to iron) redox inactive metal, serves as an important component of antioxidant defense. It contributes to maintaining redox balance through different mechanisms, e.g., is an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a co-factor of superoxide dismutase

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