In vitro and in vivo hepatic metabolism of the fungal neurotoxin penitrem A

Abstract

Penitrem A is a potent neurotoxin produced by several species in the genus Penicillium, which primarily affects the central nervous system. The toxin has several effects on neurotransmitter release, both at the central and peripheral level, as well as on ion channels. We have evaluated the hepatic metabolism of penitrem A by rat hepatocytes and rat-liver microsomes in vitro. In addition, we have conducted an in vivo study in mice and determined metabolites in several organs. According to our results, penitrem A is extensively metabolized in the liver to at least five metabolites more hydrophilic than the parent compound.

Keywords::

• Penitrem A
• Neurotoxicity
• Hepatic metabolism
• LC-MS

Acknowledgments

This study was supported by the Research Council of Norway (grant no. NFR 173498). The authors wish to thank Gunnar S. Eriksen (MSc, PhD) and Silvio Uhlig (MSc, PhD) for their helpful scientific discussions, Seyed A. Mousavi (MSc, PhD) (University of Oslo) for supplying us with rat hepatocytes, and Aksel Bernhoft (DVM, PhD) for his kindly assistance during the in vivo study. Project leader Ida Skaar (DVM, PhD) is also gratefully acknowledged for critical scientific discussions and administrative support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.