Effect of glycometabolism disorder mediated by TIGAR/PFKFB3 on liver damage in mice exposed to Cr(VI).

Various studies have shown that the harm of hexavalent chromium (Cr(VI)) to animals covers all aspects of the body, while glucose metabolism disorder is one of its hazard factors. In this study, the possible mechanism underlying Cr(VI) exposure on liver glycometabolism and damage was investigated. A mouse model was established by intragastrical administration of Cr(VI) for 5 days; liver tissues were collected and used to detect liver glycometabolism and balance between autophagy and apoptosis. Expose liver cells to a high dose of Cr(VI) significantly increased the levels of alanine aminotransferase, aspartate aminotransferase, malondialdehyde and reactive oxygen species production, suppressed glutathione peroxidase and superoxide dismutase release, upregulated 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) expression, inhibited tp53-induced glycolysis and apoptosis regulator (TIGAR) expression and promoted liver glycometabolism disorder. Moreover, the pathway network of glycometabolism has been analysised, showing that 21 differential metabolites levels were decreased and 6 increased. Carbohydrate metabolism pathways closely related to glycometabolism disorder were significantly enriched after Cr(VI) exposure. TIGAR/PFKFB3 inhibited the interactions between Beclin1/BAX and Bcl-2 via Bcl-2 regulated the balance between autophagy and apoptosis. Overall, Cr(VI) can lead to glycometabolism disorder through TIGAR/PFKFB3 imbalance and result in liver injuries in mice.