Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: in vitro testing in human liver cells.

Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: in vitro testing in human liver cells. Toxicol In Vitro. 2020 Sep 14;:105001 Authors: Acito M, Bartolini D, Ceccarini MR, Russo C, Vannini S, Dominici L, Codini M, Villarini M, Galli F, Beccari T, Moretti M Abstract It has been hypothesized that high glucose concentrations might contribute to the overall intracellular oxidative stress either by the direct generation of reactive oxygen species (ROS) or by altering the redox balance. Moreover, it has also been suggested that high glucose concentration can increase the susceptibility of DNA to genotoxic effects of xenobiotics. The aim of this approach was to test high glucose concentrations for pro-genotoxicity in human liver cells by setting up an in vitro model for hyperglycaemia. Increased cell susceptibility to genotoxic xenobiotics was tested by challenging cell cultures with 4-nitroquinoline-N-oxide (4NQO) and evaluating the extent of primary DNA damage by the comet assay. Moreover, we evaluated the relationship between glucose concentration and concentration of intracellular ROS, as well as the effects of glucose concentration on the induction of Nrf2-dependent genes such as Glutathione S-transferases, Heme‑oxygenase-1, and Glutathione peroxidase-4). To investigate the involvement of ROS in the induced pro-genotoxic activity, parallel experimental sets were set up by con...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research