Signs of how lead toxicity begins.

Signs of how lead toxicity begins

Researchers at the University of California at Los Angeles believe they've uncovered evidence of how lead, at least initially, damages the brain. Their tissue culture studies, involving mouse cells, suggest that this heavy metal not only inhibits the growth of cells making up the blood-brain barrier but also may damage the barrier's membrane so that it no longer prevents entry of substances that could disrupt normal brain function. Lead's apparent ability to make this membrane leaky could explain the brain hemorrhages, tissue swelling and nerve dysfunction seen in people suffering from acute lead toxicity, according to an account of the research in the most recent (June 30) TOXICOLOGY AND APPLIED PHARMACOLOGY.

The researchers studied the endothelial cells that make up those capillaries in the brain that serve as the blood-brain barrier. Ordinarily, explains Karen Maxwell, one of the researchers, these cells prevent transfer of all but a few essential nutrients -- like glucose -- into the brain from the blood.

In their studies, the researchers incubated endothelial cells in a normal cell-growth medium to which they had added fetal-calf blood serum containing inorganic lead. At those lead concentrations normally regarded as acutely toxic -- for example, 60 to 80 micrograms of lead per declitier (mu g/dl) of serum -- the researchers witnessed a number of adverse cell-function changes, all of which grew more pronounced as lead concentrations increased. Among these changes were an inhibition of cell growth; a reduction in the transport of blood glucose, the brain's energy source; and a reduction in "cell drinking" -- the capture of substances from the fluid outside the cell by the cell's membrane. At lower concentrations of lead, such as 40 mu g/dl, they saw no cell changes. Taken together, the researchers say, these findings suggest that the membrance of these cells may be lead's initial target.

Lead toxicologist Bruce Fowler of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., characterized the work as "potentially a very significant finding." However, adds Fowler, still to be resolved is whether this membrane effect is the sole early mechanism of lead toxicity or one of several.