Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-κB pathway and reduction of anti-inflammatory mediator expression in the kidney

Hongrui Guo,Xi Peng,Huidan Deng,Bangyuan Wu,Junliang Deng,Kejie Chen,Hengmin Cui,Zhicai Zuo,Xun Wang,Jing Fang

doi:10.18632/oncotarget.5759

Hongrui Guo, Xi Peng + Show 8 more

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https://doi.org/10.18632/oncotarget.5759

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Journal: Oncotarget	Publication Date: Sep 21, 2015
Citations: 46	License type: cc-by

Affiliation: Sichuan Agricultural University

Abstract

Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic effects. Kidney is the major organ for Ni accumulation and excretion. There are no investigations on the Ni- or Ni compounds-induced renal inflammatory responses in human beings and animals at present. Therefore, we determined NiCl2-caused alteration of inflammatory mediators, and functional damage in the broiler's kidney by the methods of biochemistry, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Dietary NiCl2 in excess of 300 mg/kg caused the renal inflammatory responses that characterized by increasing mRNA expression levels of the pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the activation of nucleic factor κB (NF-κB), and decreasing mRNA expression levels of the anti-inflammatory mediators including interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl2 caused degeneration, necrosis and apoptosis of the tubular cells, which was consistent with the alteration of renal function parameters including elevated alkaline phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine triphosphatase (Na(+)/K(+)-ATPase), calcium adenosine triphosphatase (Ca(2+)-ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) in the kidney. The above-mentioned results present that the activation of NF-κB pathway and reduction of anti-inflammatory mediator expression are main mechanisms of NiCl2-caused renal inflammatory responses and that the renal function is decreased or impaired after NiCl2-treated.

Highlights

Nickel (Ni) is a metal of widespread distribution in the environment
This study focuses on NiCl2-induced renal inflammatory responses in the kidney
The results showed that NiCl2 enhanced transcription factor NFκB and TNF-a, COX-2, IL-1β, IL-6, IL-8 and IL-18 mRNA expression levels, and nucleic factor κB (NF-κB) protein expression levels in the kidney

Summary

Introduction

Nickel (Ni) is a metal of widespread distribution in the environment. Ni is a nutritionally essential trace metal for several animal species, micro-organisms and plants, and either deficiency or toxicity symptoms can occur when too little or too much Ni is taken up [1]. Zheng et al [9] have reported that nickel sulfate (NiSO4) induces oxidative stress and apoptosis in Carassius auratus liver. Nickel oxide nanoparticles (NiONPs) and NiSO4 can cause pulmonary inflammation and significant increase of interleukin-6 (IL-6) and interleukin-8 (IL-8) protein expression levels after 24 h treatment [10,11,12]. Nickel chloride (NiCl2) elevates the protein expression of nucleic factor κB (NF-κB) and cyclooxygenase-2 (COX-2) in Beas-2B Cells [13]. Our previous studies have shown that dietary NiCl2 in excess of 300 mg/kg can cause immunotoxicity, oxidative damage and apoptosis in the kidney, spleen, small intestines and cecal tonsil of broilers [17,18,19,20]

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