Elemental imbalance elicited by arsenic and copper exposures leads to oxidative stress and immunotoxicity in chicken gizzard, activating the protective effects of heat shock proteins

Arsenic (As) and copper (Cu) are ubiquitous pollutants that pose a threat to the environment. Our aim is to study the underlying mechanisms by which As and Cu act on the chicken gizzard. In order to detect ionic disorders in chicken gizzard under chronic treatment with As³⁺ and/or Cu²⁺ and whether they can induce oxidative damage as well as immune disorders, 30 mg/kg arsenic trioxide (As₂O₃) and/or 300 mg/kg copper sulfate (CuSO₄) were added to the chicken's basal diet. After 12 weeks of exposure, trace elements were found to have significant interference, accompanied by damage to the antioxidant system. In addition, As³⁺ and/or Cu²⁺ activated the nuclear factor kappa B (NF-κB), inducing severe inflammation. At the same time, damaged structural integrity which might be caused by inflammation was discovered after hematoxylin and eosin (H&E) staining. Moreover, symbolic Th1/Th2 (Th, helper T cell) drift was also observed in treatment groups, meaning that immune function is left to be affected, and the increment in heat shock proteins may be a self-protective mechanism of gizzard. Interestingly, we found that the damage to the gizzard of chicken was aggravated in a time-dependent manner, and the combined exposure was more pathogenic than the single exposure, of which the mechanism needs further exploration. Together, this work helps move us toward a better understanding of the molecular mechanisms that mediate the interactions between Cu excess and As³⁺ exposures and possible health consequences in susceptible species.