Effects of alcohol ingestion on zinc content of human and rat central nervous systems

The abundance of zinc in hippocampal mossy fibers has stimulated investigation of zinc status in various pathologic states in which behavioral or anatomic deficits involving the hippocampus are known to occur. Limited autopsy studies of chronic alcoholic humans have suggested that the content of zinc might be reduced in several brain regions whereas reported attempts to replicate these findings in ethanol-exposed experimental animals have produced inconsistent results. In this comparative study, the zinc concentration in 10 brain regions, all spinal cord segments, and microdissected hippocampal subfields was measured by isotope ratio mass spectrometry. A widespread 15 to 20% reduction in zinc content was observed in all regions of chronic alcoholics compared with controls but a selective involvement of hippocampus was not detected. In the experimental studies, groups of rats were exposed to ethanol by one of three routes: inhalation for 2 weeks, as an ethanol/liquid diet for 3 months, or a single intoxicating i.p. dose. Determinations of tissue uptake of radiozinc and of total zinc content were made. In contrast to human pathologic material, zinc pool size and tissue uptakes were not affected by experimental ethanol administration by any route. This study confirmed that a reduction in zinc concentration occurs in the central nervous system of chronic alcoholics. The animal studies indicated, however, that simple ethanol exposure, even for prolonged periods, does not perturb zinc metabolism in brain. Together, these observations argue that the abnormalities of zinc metabolism in chronic alcoholics are possibly secondary to homeostatic alterations associated with hepatic failure.