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

// Hongrui Guo 1,* , Huidan Deng 1,* , Hengmin Cui 1,2 , Xi Peng 1,2 , Jing Fang 1,2 , Zhicai Zuo 1,2 , Junliang Deng 1,2 , Xun Wang 1,2 , Bangyuan Wu 1 and Kejie Chen 1 1 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an, Sichuan, China 2 College of Veterinary Medicine, Sichuan Agricultural University Ya’an, Sichuan, China * These authors have contributed equally to this work Correspondence to: Hengmin Cui, email: // Jing Fang, email: // Keywords : NiCl , inflammation; NF-κB, mRNA expression, kidney, Immunology section Received : July 11, 2015 Accepted : August 26, 2015 Published : September 21, 2015 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 NiCl 2 -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 NiCl 2 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, NiCl 2 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.