Interplay between elemental imbalance-related PI3K/Akt/mTOR-regulated apoptosis and autophagy in arsenic (III)-induced jejunum toxicity of chicken.

Arsenic trioxide (AsO), the most toxic form of arsenic found in foodstuffs, is considered a carcinogen for human and animal. But many of the events that occur during its passage through the gastrointestinal tract are uncharted in birds. This study assesses the toxic effect on the jejunum of chicken which subchronically exposed to diets that contain AsO (0, 0.625, 1.25, 2.5 mg/kg body weight) for 90 days. Electron microscopy, TdT-mediated dUTP nick-end labeling (TUNEL), qPCR, and Western blot were performed. The results showed that mitochondrial fusion and apoptosis inhibiting genes had degressive trends, whereas mitochondrial fission and apoptosis activating genes presented heightened expressions in the treatment group compared with the control (P < 0.05). Subsequently, significant inhibition in PI3K/AKT/mTOR signaling was observed. Moreover, the expression of autophagy markers (LC3-II/LC3-I, Beclin-1) increased time and dose-dependently. Additionally, metabolic disorders of trace elements were detected evidenced by their significant decreases (aluminum, silicon, calcium, manganese, strontium, titanium, lithium, boron, cobalt, mercury, chromium) and increases (arsenic, cadmium, selenium, lead, nickel) on 90 days using inductively coupled plasma mass spectrometer (ICP-MS). It is possible that the changes of trace elements have a hand in the come on and development of arsenism. Taken together, we conjectured that, in chicken jejunum, arsenic led to redistribution of trace elements, promoting apoptosis via regulating mitochondrial dynamics, leading to autophagy through PI3K/AKT/mTOR signal pathways.