By Joy Carter From UAB Magazine, Spring 2000 (Volume 20, Number 1)

The war is on. Harmful pollutants are waging an all-out assault on the human body. From man-made toxicants, such as industrial waste and automobile exhaust, to naturally occurring invaders, such as bacterial toxins in the water supply, toxicants are formidable foes. But the human body is a worthy adversary—and it can increase its ability to defend itself.

Toxic Truces

Our defenses are twofold—both natural and adaptive, according to Henry Jay Forman, Ph.D., chair of the Department of Environmental Health Sciences in UAB’s School of Public Health. “Throughout evolution, species have adapted—changed—as a result of exposure to environmental agents,” he explains. “In fact, as organisms have mutated over time, if a mutation presented an advantage in terms of survival, biology found a way to use it.”

Oxygen is an example of a toxicant that humans and most other living things have learned to use in order to survive. “At the beginning of life on this planet, there was not much, if any, oxygen,” says Forman. “When oxygen came into the atmosphere, it was toxic—and still is at high concentrations—but we’ve adapted to it at a certain level. We live with 20-percent oxygen in the atmosphere, because we’ve developed natural defenses against it and have learned to use it.”

Like other toxicants that we’ve turned to our advantage, oxygen has both a bright and a dark side. “The advantage of oxygen is that it allows cells to produce energy 18 times more efficiently than they could otherwise manage to do,” says Forman. “The downside is that, as part of this energy production process, chemical reactions trigger the formation of oxygen free radicals—potentially toxic molecules that can damage cells.”

But even free radicals aren’t all bad, Forman notes. Although these molecules can damage multiple targets in cells, they also play a vital role in fighting infection. White blood cells produce these toxic molecules in order to kill bacteria and fungi. “But even that beneficial process can go sour,” says Forman. “Pus, a common sign of infection, is the accumulation of dead white cells—partially the result of white cells damaging themselves with the free radicals they produce.”

The Antioxidant Arsenal

Such paradoxical chemical reactions—producing both beneficial and destructive results—are taking place in the body all the time. Understanding these reactions and the role they play in the body’s response to toxicants is the primary focus of Forman’s research. He is particularly interested in a molecule called glutathione (pronounced glu ta-thi-own), an antioxidant produced naturally in our bodies from the breakdown of the proteins we eat.

“Antioxidants are essential for ridding the body of toxicants,” says Forman. “Vitamin E and vitamin C are antioxidants that we derive from eating fruits and vegetables or taking vitamin supplements,” he continues. “Glutathione is exceptional in that we make it ourselves—and, in terms of its concentration, it is the most abundant antioxidant we have in our cells.”

About 10 years ago, Forman played a key role in discovering that the body has the ability to increase production of this essential antioxidant as a result of exposure to toxicants. “Toxicants ‘stress’ the body, prompting an adaptive response that raises the body’s defenses,” says Forman. “Exposure to a sub-lethal dose of a toxicant elicits a response to produce more glutathione. Then, when the body is exposed to that same toxicant again, there is greater tolerance, because there is more glutathione present, and there is the ability to produce more glutathione rapidly.”

Glutathione and other antioxidants are the body’s first defense against oxidant injury. “Antioxidants are barriers against potential cell damage to every organ of the body,” says Forman.

Certain enzymes may also play a role in defending against toxicants by metabolizing them into less dangerous molecules. “These enzymes can be produced by the body in response to sub-lethal exposure to toxicants,” says Forman. “They work in concert with glutathione to defend against toxicants.”

Defeating Disease?

Understanding glutathione—increasing our basic, scientific knowledge about the antioxidant and how it works—is Forman’s goal. “We know certain things about glutiathione, but much remains unexplained,” he says. “We know, for example, that the body reacts to toxicants by accelerating the production of glutathione, and we know this increase is helpful in adapting to and fighting oxidants. But we don’t know the entire mechanism by which the increase occurs or what other functions it may play.

“We also know that people can tolerate some level of exposure to toxicants, and we know this tolerance involves the mechanisms associated with increasing glutathione. But we don’t know to what point you must increase your defenses in order to avoid damage.”

While Forman and his colleagues may be years away from the answers they’re seeking, the implications of their research are great.

“Potential applications will come once we understand how these biological processes play out in real individuals who may have differing degrees of susceptibility to oxidative damage,” says Forman. “For instance, we know that asthmatics are particularly susceptible to injury from oxidants, but we don’t know if their ability—or perhaps lack of ability—to produce glutathione has anything to do with that vulnerability. Research will tell.”

Forman’s research may also point the way to advances in the treatment of certain viral diseases. “We know that some viruses produce oxidative stress,” he says, “and other researchers have shown decreased levels of glutathione in people with viruses such as HIV. Although we know decreased levels of glutathione are unhealthy, we don’t yet know if the decrease has anything to do with the pathology of the virus.

“With more knowledge, we may eventually be able to establish a definitive link between certain disease states and low levels of glutathione. One day, we may even be able to fight diseases by giving people drugs to stimulate the production of glutathione. But much more research is needed before we can approach such exciting possibilities.”

On the ambiguous battlefield of biological adaptation to toxicants, Forman emphasizes that the smartest strategy is to follow nature’s lead—to learn everything we can about our enemies so that we can use them for our benefit.

	LINKS TO RELATED INFORMATION UAB Department of Environmental Health Sciences UAB School of Public Health Comments? Questions? E-mail the editor: Pam.Powell@VPUADV.UAB.EDU