Hormone Shows Promise to Combat Alcohol Poisoning and Intoxication Effects

Not only does the liver play a role in alcohol metabolism, but it also sends a hormonal signal to the brain to defend against the negative symptoms of drunkenness, such as slurred speech and the inability to keep your balance.

In a study published in the journal Cell Metabolism, researchers found that a hormone known as fibroblast growth factor 21 (FGF21) protected mice against the effects of ethanol on their ability to maintain their balance and activate their righting reflex.

There are many reasons a person may want to "de-intoxicate" himself, but the University of Texas Southwestern concentrates on only one of these causes: alcohol poisoning. Not only is alcohol poisoning the top cause of mortality among younger individuals, but in the United States alone, an average of six people pass away from the effects of alcohol poisoning every single day.

Suppose the researchers at UT Southwestern can develop a "therapy" for human intoxication that is based on FGF21. In that case, it may become unnecessary to do more complex procedures, such as stomach pumping, which would result in the annual saving of hundreds or thousands of lives.

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Ethanol-consuming mice produce more of a protein known as fibroblast growth factor 21 (FGF21), which shields them against the loss of balance and righting reflex that ethanol consumption causes. The research discovered that mice missing the hormone required substantially longer than their wild-type littermates to restore their righting reflex and equilibrium following exposure to ethanol. This was attributed to the fact that FGF21 efficiently conveys messages to the brain, accelerating the recovery process after intoxication. According to the study results, it may be possible to treat acute alcohol intoxication using drugs that target the FGF21 liver-brain pathway.

Both mouse and human livers produce the hormone FGF21. Prior study indicates that alcohol use is the primary trigger for FGF21 synthesis in humans, with the protein lowering alcohol cravings and protecting the liver from alcohol-induced damage. Alcohol consumption may be affected by variations in FGF21's genes and receptors.

Steven Kliewer, David Mangelsdorf, and their team at the University of Texas Southwestern Medical Center were studying FGF21 when they discovered that mice lacking the ability to produce the hormone take twice as long to regain consciousness following an intoxicating dose of ethanol - the form of alcohol found in drinks - compared to mice that produce FGF21.

In order to get more insight into the matter, the research group administered an excessive amount of ethanol to mice with normal levels of FGF21 production. After then, the mice received more FGF21 through injection.

After being knocked out by the ethanol, it took the animals that had been given the injection just half as much time to regain awareness and stand up compared to mice who had not been given the injection. They were also able to regain their coordination more quickly.

According to Kliewer, "here's this whole new mechanism where the liver sends out a distress signal to the brain to limit the symptoms of intoxication." "We know the liver's significance in breaking down ethanol," adds Kliewer. "But here's this whole new pathway where it happens."

An examination of alcohol retention in 85 different animals indicates which ones are the best.

In a different phase of the experiment, FGF21 did not influence the capacity of a group of mice to recover from being sedated by medicines like ketamine. This finding shows that the hormone's sobering effect is only seen in conjunction with alcohol consumption. "That suggests that there are unique neurons in that area of the brain that are likely engaged in diverse reactions to different circumstances," says Mangelsdorf. "It's quite probable that these different neurons are responsible for different behaviors."

In addition, the researchers observed that FGF21 acts on neurons in an area of the mouse brain known as the locus coeruleus, which is responsible for the production of the neurotransmitter noradrenaline. This area is responsible for regulating wakefulness and awakening from sleep.

Drinking alcohol causes an increase in the quantity of noradrenaline generated by the brain in persons. According to Kliewer, this might be caused by FGF21, which would imply that giving inebriated individuals FGF21 could also assist them in becoming sober.

While more study is necessary, an FGF21 injection could be administered to patients who come to the hospital suffering from severe alcohol intoxication. When the patient has regained consciousness and is lucid, the medical staff will be able to interrogate them and begin treatment more quickly.

According to Matthew Gillum, who researches FGF21 at the Danish pharmaceutical firm Novo Nordisk, the results strengthen our developing knowledge of the link between the hormone and the use of alcoholic beverages.

Ethanol is the component that is contained in alcoholic drinks that causes intoxication. The researchers conducted their experiments on two different strains of mice by administering the hormone to them after first injecting them with a "binge dosage" of ethanol. It took the mice without FGF21 more time to recover from the injection than the animals with FGF21.

In a different experiment, they treated the mice with ethanol once again. Then about one hour later, when the animals were still unconscious, a dosage of recombinant FGF21 was administered to them. According to what the researchers noted, this cut by half the length required for both male and female mice to "recover their righting reflex."

The research team noticed the mice's "righting reflexes," or their ability to get back up on their feet after being put on their backs. This allowed them to determine that animals missing FGF21 stayed inebriated longer than ordinary mice.

In addition, the researchers investigated the impact of an additional dose of FGF21 on mice that had been given alcohol. The mice who were given an extra dosage of the hormone sobered up almost an hour and a half sooner than the control inebriated animals. This difference was statistically significant.

According to the research findings, FGF21 reduces the impairments to one's cognition and coordination brought on by alcohol use and hastens the recovery process from alcohol-induced intoxication. It was established that the hormone's capacity to stimulate the noradrenergic nervous system, a collection of nerve cells in the brain that governs alertness, was the cause of these "sobering" effects. This was determined by observing how the hormone affected the system's activity.

While this research was carried out on mice rather than people, the findings point to FGF21 as a potential therapy option for alcohol intoxication in humans, which may be fatal if left untreated. In addition, Gizmodo reports that more clinical studies have already been conducted to investigate the hormone for other possible uses. This gives confidence to the possibility that FGF21 might be used safely in the future as a treatment.

Their studies suggest that FGF21 might be useful for treating the many patients who come into emergency rooms with acute alcohol poisoning.

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                       Drunk mice sober up after a hormone shot