Muscle Morbidity and Reduced Regenerative Capacity
While the widely reported incidence of arsenic use in past centuries for medicinal, industrial, and homicidal purposes has declined dramatically, modern times have seen a resurgence in the attention paid to this organic metalloid. This is due, in large part, to the increasingly recognized presence of arsenic in the food and drinking supplies serving more than 140 million individuals worldwide and nearly 4 million individuals in the United States alone. Unfortunately, the very same characteristic that makes arsenic such an effective tool for acute poisoning also makes it a dangerous environmental contaminant: it is largely undetected because it is odorless, tasteless, and colorless. Increasingly, however, arsenic is being recognized for its adverse, yet clandestine, effects on tissue functioning and regenerative capacity—even at low, everyday concentrations.
In addition to causing a number of cancers and non-cancer diseases, chronic arsenic exposure causes significant muscle weakness and dysfunction. Sensorimotor impairment and muscle atrophy are observed in 10-14 million individuals exposed daily to arsenic in their drinking water. Thus, in a very significant population, environmental exposure may be surreptitiously contributing to skeletal muscle dysfunction. This is important, as muscle weakness is among the greatest factors contributing to declines in functional mobility and is a strong predictor of mortality.
Collaborative investigations from the laboratories of Aaron Barchowsky, PhD, professor in the Department of Environmental and Occupational Health at the University of Pittsburgh, and McGowan Institute for Regenerative Medicine affiliated faculty member Fabrisia Ambrosio, PhD, MPT, assistant professor and research scientist in the Department of Physical Medicine and Rehabilitation, have recently demonstrated that environmentally-relevant levels of arsenic found in drinking water dramatically disrupts muscle composition and impairs metabolic functioning. It is hypothesized that these effects contribute to the common symptoms of weakness and fatigue in exposed individuals. Moreover, Drs. Ambrosio, Barchowsky, and McGowan Institute for Regenerative Medicine faculty member Donna Stolz, PhD, have found that muscle stem cells are direct targets of arsenic exposure, findings which may have important implications for how well an individual is able to heal after a traumatic injury or a surgical procedure, for example.
The NIH has recognized the widespread importance of this line of investigation, as evidenced by a grant totaling over $2 million recently awarded to Drs. Barchowsky and Ambrosio. This project will investigate the underlying mechanisms for skeletal muscle morbidity and lost regenerative capacity caused by arsenic exposures.