Salsolinol compounds as biomarkers for human alcohol consumption, disease, and toxicity

Abstract

View Poster

Alcohol abuse and alcoholism are among the most significant public health issues of our time and is arguably mankind’s oldest drug. The economic cost to Americans is more than $225 billion dollars annually. It is estimated that alcoholics have an average decrease in life expectance between 12-15 years. Despite the enormous amount of research, there has yet to be a mechanism proposed that accounts for the many different behavioral, neurochemical, or toxicological effects associated with alcohol use and abuse.

Upon alcohol administration, ethanol’s primary metabolite, acetaldehyde, readily forms salsolinol and salsolinol-like compounds in the periphery as well as the brain. Alcoholics have elevated levels of salsolinol-like compounds in urine and post mortem brain samples. Moreover, studies have shown that these salsolinol-like compounds can induce Parkinson like neurodegeneration.

Swiss-Webster mice were treated with saline (control), l-dopa, or ethanol, with or without pretreatment of pargyline, benserazide, tolcapone, or disulfiram. After times of 5, 10 or 30 mins animals were sacrificed. Whole brains were removed and dissected on ice into striatum, hippocampus cerebellum, and the rest of the brain sections. Urine, blood, and liver were also collected for analysis.

Several salsolinol like compounds were determined in the blood, liver and striatal brain sections at 5 and 10 minutes. However, by 30 minutes, these salsolinol like compounds were mostly the methoxy metabolites. This work provides evidence that these acetaldehyde derived toxic compounds get into the brain and are circulating in the blood for at least up to 30 minutes.