Cadmium exposure causes mitochondrial fission and fusion disorder in the pig hypothalamus via the PI3K/AKT pathway

Cadmium (Cd) is the main environmental pollutant causing endocrine and nervous system dysfunction in ani-mals. High doses of Cd cause cytotoxicity, including programmed necrosis and apoptosis, which has aroused widespread concern. Mitochondrial dynamics plays a key role in programmed necrosis and apoptosis of endo-crine organs. Nevertheless, there is a lack of information on the relationship between Cd-induced programmed necrosis/apoptosis of the hypothalamus and the mitochondrial fusion-fission balance. Therefore, a hypothalamic injury model of Cd exposure was established by adding 20 mg/kg CdCl2 to the basic pig diet for 40 days. Analysis of the Cd toxicity mechanism was conducted by inductively coupled plasma mass spectrometry, hematoxylin and eosin staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and quanti-tative reverse transcription-polymerase chain reaction, as well as western blot analyses. The results suggested that exposure to Cd inhibited the expression of PI3K and AKT, interfered with the balance of mitochondrial fusion and division, downregulated the expression of Mfn2, Mfn1, and OPA1, and upregulated the expression of Drp1 and Mff, which led to cell apoptosis and programmed necrosis in the pig hypothalamus. This study finds that cadmium exposure leads to mitochondrial fission and fusion dysfunction in porcine hypothalamus via the PI3K/AKT pathway.

Automated summary

Cadmium exposure leads to mitochondrial fusion and fission dysfunction in porcine hypothalamus, resulting in cell apoptosis and programmed necrosis.