Copper or/and arsenic induce oxidative stress-cascaded, nuclear factor kappa B-dependent inflammation and immune imbalance, trigging heat shock response in the kidney of chicken

Abstract

Excessive amount of copper (Cu) and inorganic arsenic (iAs) coexists in drinking water in many regions, this is associated with high risk of nephropathy, defined as chronic structural and functional disorders of the kidney. However, the underlying mechanisms are not well understood. In this study, a total of 72 day-old Hy-line chickens were exposed to 300 mg/kg copper sulphate or/and 30 mg/kg arsenic trioxide for 12 weeks. Indicators of oxidative stress, inflammation and heat shock proteins (HSPs) production were analyzed in kidney. The results showed that, when the toxicant was administrated alone, there is an antagonism between redox homeostasis during the first 4 weeks, which follows a collapse of antioxidant system manifested by damaged biomembrane structure. What's worse, oxidative damage-cascaded histopathological lesions were accompanied by increases of proinflammatory mediators and an imbalance of “Th1/Th2 drift” (Th, helper T cell) regulated by nuclear factor kappa B (NF-κB). Simultaneously, intense heat shock response went with the organism. The above-mentioned renal lesions and indicators changes were time-dependent, more complex and deteriorated effects were observed in Cu/iAs combined groups compared with the others. This study supports Cu and iAs have a synergistic type on the nephro-toxicological process additively. In conclusion, oxidative stress and inflammatory induced by Cu or/and iAs are potential mechanisms in their nephrotoxicity, increased heat shock response may play a renoprotection function in tissues damage.

Chlorpyrifos induces redox imbalance‐dependent inflammation in common carp lymphocyte through dysfunction of T‐cell receptor γ

“…TCR signalling pathways are differentially affected by physiological levels of oxidative stress and further induced T‐cell hyporesponsiveness (Cemerski, Cantagrel, Van Meerwijk, & Romagnoli, ). Except that, Wang et al () found copper‐ and arsenic‐induced oxidative stress in the kidney of chicken, which further triggered NF‐κB‐dependent inflammation and immune imbalance. In the present study, we found that TCR γ knockdown induced a large amount of ROS released in lymphocytes; meanwhile, antioxidant system is inhibited.…”

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

“…Moreover, existing evidence demonstrates that heat-induced oxidative stress and ER stress are responsible for various types of injury to cells, tissues, and organs in chickens and other species. These include apoptosis, immune imbalance in the intestines, and nephropathy [10][11][12][13]. A recent study reported the use of antioxidants to protect the testis against the adverse effects of HS [14].…”

Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan

“…Studies have found that exposure to heavy metals and other trace elements may compromise various aspects of the immune system. Among these elements, arsenic (As), cadmium (Cd) and lead (Pb) have received more attention and investigations [ 1 , 2 , 3 , 4 , 5 , 6 ]. Cell culture study shows that the chemotherapeutic agent arsenic trioxide could inhibit early T cell cytokine production.…”

“…Studies on relationships between heavy metal exposure and immunological effect using in vivo and in vitro methods are with conflicting results [ 2 , 8 ]. Limited studies have observed effects of trace elements on humans using immunologic indicators.…”