Cocaine abuses liver lipid metabolism

August 27, 2012 § Leave a comment

Medicinal cocaine. Image from http://en.wikipedia.org/wiki/File:Cocaine_hydrochloride_CII_for_medicinal_use.jpg

Cocaine wrecks an abuser’s heart, brain and liver. In a paper just out in the Journal of Lipid Research, investigators have figured out that cocaine disrupts the metabolism of lipids of the liver. They think their finding suggests a way to help mitigate the symptoms of cocaine abuse.

According to the National Institute on Drug Abuse, 4.8 million Americans 12 years old and older snorted, smoked or injected cocaine in 2009. The drug is a strong stimulator of the central nervous system and increases the level of dopamine, a neurotransmitter associated with pleasure. If abused, cocaine does a number on the body: Constricting blood vessels, dilating pupils, increasing blood pressure, and causing stomach aches and nausea are just a few of the symptoms. (Because it can constrict blood vessels, cocaine is used in hospitals for medicinal purposes to stop bleeding.)

Damage to the liver is one of the major causes of death in cocaine abusers. But not much is known how exactly cocaine damages the liver. Chi Chen at the University of Minnesota explains that, while it’s understood that the liver metabolizes cocaine into reactive metabolites, “what happened between the metabolic activation of cocaine and the magnification of the toxicity was not clear.”

One of the telltale signs in the liver is the accumulation of lipids before necrotic cell death in the liver. So Chi and colleagues analyzed all the lipids in the liver. They had two sets of test mice: ones that were given cocaine and ones that were not. When they looked at all the lipids in the liver from the two sets of mice, the investigators found that the cocaine-ingesting animals suffered from a progressive inhibition of mitochondrial fatty-acid oxidation.

Fatty-acid oxidation is mostly regulated by a transcription factor called PPARα. When the investigators treated the cocaine mice with an activator of PPARα called fenofibrate, they found that the liver was largely protected.

Chen says that his group’s work seems to suggest that treatment with a drug that helps push along metabolism “could potentially prevent or reduce damage caused by cocaine treatment, not only in the liver, but also in other parts of the body, such as cardiovascular system.”

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