- A tiny protein called metallothionein (MT) may protect against alcohol's neurotoxic effects.
- The brain can make more of these proteins in response to alcohol consumption.
- One of an individual's different responses to alcohol may be related to his or her MT levels.
- Research indicates that MT can serve as an antioxidant throughout the body, including the brain.
"Alcohol's toxicity," explained Yutaka Suzuki, visiting scientist from the department of neurology at the Nihon University School of Medicine and lead author of the study, "could be due to its production of oxygen radicals. Metallothionein may protect against oxidative damage of the central nervous system that is caused by overproduction of free radicals."
MT was initially identified in 1957 as a cadmium-binding protein. It has since been discovered to also bind with and regulate a variety of essential trace minerals, such as zinc and copper. Research suggests that both a deficiency as well as an excess of some minerals can cause heart disease, diabetes, high blood pressure and cancer.
The MT protein interests toxicologists because it may protect against metal toxicity and possibly against oxidative stress. It interests pharmacologists because it might have a role in cancer chemotherapy. Nutritionists are interested because it appears to be a major storage protein for zinc, which is of particular importance during fetal development. Biochemists and molecular biologists might be interested in the regulation mechanisms of an extremely inducible protein. And now addiction researchers are interested in MT's function in relation to alcohol's neurotoxic effects.
"This is one of the first few studies that has looked at the expression of metallothionein in the brain," said Michael Aschner, professor of physiology and pharmacology at Wake Forest University School of Medicine. "There are different types or forms of metallothioneins in the body, and we don't know exactly what they're doing, but we do know that they're very important in terms of regulating the concentrations of different metals. They're also likely to be quite important in protecting tissues from various insults such as high oxygen levels." In other words, drinking alcohol may lead to systemic stress by producing oxygen radicals which can, in turn, produce or "up-regulate" metallothionein in order to counter or protect against alcohol's effects.
"Different responses of people to alcohol," said Suzuki, "may be explained in part by the presence of proteins such as metallothioneins. Different levels of this protein - both existing and produced in response to drinking - might explain different levels of alcohol-related toxicity in people."
Aschner described two groups of people who may one day benefit from Suzuki's research. "As people age," he said, "the levels of compounds or anti-oxidants such as metallothionein tend to decrease. So you could say that someone who is older may have less of an ability to defend themselves, their brains may not be able to compensate for insults." Drinking alcohol could produce the kind of neurotoxic "insults" noted by Aschner.
Another at-risk group includes those who are already ill. "Let's say that an individual is already immunologically compromised by stress or illness," said Aschner. "They have inflammation within the brain, for example, that has already compromised their immune response. If they drink on top of this illness, they may not be able to produce as much metallothionein to counteract the neurotoxic effects of alcohol, which places them at greater risk of alcohol-related damage."
Although this study's results may not have immediate research or practical applications, both Aschner and Suzuki noted the importance and necessity of painstakingly adding to the body of alcohol research, molecule by molecule.
"Other findings have suggested that alcohol leads to oxidative stress," said Aschner, explaining the study's position in a continuum of alcohol research. "This is a mechanistic study trying to elucidate metallothionein's function relative to alcohol's neurotoxicity. This doesn't mean that we can start manipulating people's genes, putting more metallothionein in their genetic makeup so that they can drink more alcohol. This study investigated whether metallothionein provides resistance to alcohol's effect."
Suzuki plans to build upon his research findings. "I would like to study levels of metallothionein in the brains of people who suffer from diseases related to alcohol," said Suzuki. "Metallothionein is only one of several factors involved."
Co-author of the Alcoholism: Clinical & Experimental Research paper was M. George Cherian of the Department of Pathology, Health Sciences Centre, at the University of Western Ontario. The study was funded by the Medical Research Council of Canada.