Alterations of antioxidant indexes and inflammatory cytokine
expression aggravated hepatocellular apoptosis through mitochondrial
and death receptor-dependent pathways in Gallus gallus exposed
to arsenic and copper
Received: 22 January 2018 /Accepted: 13 March 2018 /Published online: 22 March 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
In this study, we sought to investigate the effects of sub-chronic exposure of arsenic (As) and copper (Cu) on oxidative stress,
inflammatory response, and mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two 1-day-old male
Hy-line chickens were treated with basal diet, 30 mg/kg arsenic trioxide (As
), or/and 300 mg/kg copper sulfate (CuSO
8, and 12 weeks. Study revealed that exposure to As or/and Cu undermined the antioxidant function and increased lipid
peroxidation. Worse yet, liver cell swollen, vacuolar degeneration, and inflammatory cell infiltration were accompanied by an
increase of the nuclear factor-κB(NF-κB) and its downstream inflammation-related genes after exposure to As or/and Cu.
Furthermore, mitochondria swollen and chromatin condensation were found in As and Cu groups, and hepatocyte nuclear
membrane rupture and markedly increased (P < 0.01) apoptosis index were observed in As combined with Cu group.
Meanwhile, the transcription and protein expression levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c),
and caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated in As, Cu, and As + Cu groups in the
liver tissues (P <0.05,P < 0.01). Our results indicated that exposure to As or/and Cu could lead to oxidative stress, inflammatory
response, and tissue damage and aggravate hepatocellular apoptosis through mitochondrial and death receptor-dependent path-
ways in chicken liver. And As and Cu showed a possible synergistic relationship in liver damage.
Keywords Chicken liver
Arsenic (As) is a well-known environmental toxicant. Arsenic
compounds have been used as in pesticides, herbicides, fun-
gicides, in metal smelters, and mining and thus widely exist in
soil and drinking water (Mandal and Suzuki 2002). The World
Health Organization (WHO) sets the maximum contaminant
level (MCL) of As at 10 μg/L (Ma et al. 2017), whereas high
content inorganic arsenic (iAs) was found in drinking water
available in Taiwan and increased risk of skin cancer and lung
squamous cell carcinoma (Wu et al. 2016a). Appropriate die-
tary copper (Cu) supplements are sufficient to improve mito-
chondrial function and activity of respiratory complexes
whereas excessive uptake of Cu induces kidney damage, liver,
and gastrointestinal distress (Galhardi et al. 2004; Zietz et al.
2003). Furthermore, copper sulfate (CuSO
) was previously
used as a biocide and an algaecide to control the growth of
phytoplankton in aquatic ecosystems (Gautam et al. 2018).
Due to its high solubility in water, it can easily contaminate
the environment. Thus, it can be seen that animals and humans
are inevitably exposed to As or Cu through ingestion of con-
taminated food and drinking water. And in the real world,
pollutants usually exist as mixtures. Metal mixture has
Juanjuan Liu and Hongjing Zhao contributed equally to this work.
Responsible editor: Philippe Garrigues
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11356-018-1757-0) contains supplementary
material, which is available to authorized users.
* Mingwei Xing
Department of Physiology, College of Wildlife Resources, Northeast
Forestry University, Harbin 150040, Heilongjiang, People’sRepublic
Environmental Science and Pollution Research (2018) 25:15462–15473