Insights into CdTe quantum dots induced hepatotoxicity: Regulation of cytochromes P450 isoenzymes function in liver microsomes from in vivo and in vitro studies.

The widespread use of QDs raises health and environmental concerns, and the ROS induced oxidative stress is reported as the main mechanism of QDs toxicity. Cytochrome P450 (CYP450) superfamily, the primary enzyme system for metabolizing external compounds in the liver, also generates reactive oxygen species (ROS), making it crucial for detoxification and ROS production. Therefore, we investigated whether QDs could cause liver tissue damage by affecting the activity of CYP450 isoenzymes (CYP1A2, CYP2E1, CYP2D2, and CYP3A1) in liver microsomes, thereby altering ROS generation. This mechanism has not been previously reported. Our experiments indicate that CdTe QDs exhibit a dose/time-dependent relationship with the enzymatic activities of CYP1A2 and CYP2E1, which are closely related to ROS generation. However, an inconsistency was observed between the data for CYP2E1 activity in vivo and in vitro due to the complexity of in vivo regulatory factors. More importantly, in vitro experiments have shown that CdTe QDs can significantly promote the enzymatic activity of CYP1A2. Therefore, we speculate that CdTe QDs may induce ROS generation by enhancing CYP450 enzyme activities. In addition, molecular docking experiments were conducted to illustrate the impact of CdTe QDs on the structure of CYP1A2, leading to functional change (i.e., enzyme activity). These findings suggest a novel mechanism by which CdTe QDs regulate CYP450 activities in liver microsomes, particularly CYP1A2. This may represent a crucial pathway through which CdTe QDs induce excessive ROS generation, leading to oxidative stress and liver damage.