FORENSIC TOXICOLOGY

An enzyme can change the rate at which it processes one compound when another chemical is present. Whether the enzyme also turns over that second chemical is a separate question.

What the researchers saw in two systems

The investigators used human liver microsomes and nanodiscs containing CYP3A4. Enniatin B1 was metabolized in these systems, and it reduced hydroxylation of the CYP3A4 probe midazolam. The researchers did not detect CYP3A4 metabolism of deoxynivalenol under their conditions, yet deoxynivalenol altered formation of metabolites from other substrates, including enniatin B1.

What transfers to human exposure

The experiment distinguishes evidence of turnover from a change in another substrate’s reaction rate within the assay. The results depend on the compounds and concentrations tested. To evaluate a proposed interaction in a person, the relevant concentrations at the enzyme and human exposure data would be needed before assigning a clinical effect.

Source

Laboratory study of enniatin B1 and deoxynivalenol in CYP3A4 preparations (full text) · DOI