Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing

Goergens, Christian, Ramme, Anja Patricia, Guddat, Sven, Schrader, Yvonne, Winter, Annika, Dehne, Eva-Maria, Horland, Reyk and Thevis, Mario . Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing. Drug Test. Anal.. HOBOKEN: WILEY. ISSN 1942-7611

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DOI:10.1002/dta.3161

Abstract

A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher order system physiology or due to various species-specific differences using animal models. A more recently established technology for simulating human physiology is the organ-on-a-chip principle. In a multichannel microfluidic cell culture chip, 3-dimensional tissue spheroids, which can constitute artificial and interconnected microscale organs, imitate principles of the human physiology. The objective of this study was to determine if the technology is suitable to adequately predict metabolic profiles of prohibited substances in sport. As model compounds, the frequently misused anabolic steroids, stanozolol and dehydrochloromethyltestosterone (DHCMT) were subjected to human liver spheroids in microfluidic cell culture chips. The metabolite patterns produced and circulating in the chip media were then assessed by LC-HRMS/(MS) at different time points of up to 14 days of incubation at 37 degrees C. The overall profile of observed glucurono-conjugated stanozolol metabolites excellently matched the commonly found urinary pattern of metabolites, including 3 ' OH-stanozolol-glucuronide and stanozolol-N-glucuronides. Similarly, but to a lower extent, the DHCMT metabolic profile was in agreement with phase-I and phase-II biotransformation products regularly seen in postadministration urine specimens. In conclusion, this pilot study indicates that the organ-on-a-chip technology provides a high degree of conformity with traditional human oral administration studies, providing a promising approach for metabolic profiling in sports drug testing.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Goergens, Christian	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Ramme, Anja Patricia	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Guddat, Sven	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Schrader, Yvonne	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Winter, Annika	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Dehne, Eva-Maria	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Horland, Reyk	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Thevis, Mario	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED