Biochemical Effects of Cadmium Exposure and the Potential Pharmacologic Significance of Cadmium Mediated Hydrolase Inhibition.

摘要

The objective of this research was to explore the possible existence of an adverse effect resulting from exposure to cadmium (Cd) within levels allowed or recommended to be 'without adverse effect'. The central hypothesis that we tested was that the exposure of Sprague-Dawley rat to Cd (2 mg CdCl2/kg, administered i.p.) would reduce non-specific serum and tissue hydrolase activity enough to alter the metabolism of an ester compound like methylphenidate. The knowledge that metals affect the function of enzymes was the rationale behind an initial investigation attempting to identify an enzyme that could be used as a biomarker of Cd exposure. It was discovered that Cd was capable of reducing the activity of rat serum hydrolase. The hydrolases are ubiquitous enzymes that are known to be active participants in the hydrolysis of many foreign toxic and therapeutic compounds. However, the physiological role of the esterases is unclear. Therefore, we choose to first demonstrate a significant effect in vitro, then using preliminary data, speculate on the in vivo pharmacologic significance of Cd altered hydrolase activity.