Pharmacotoxicology of Trichloroethylene Metabolites

Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression

This project focuses on the kinetics, metabolism and human toxicology of dichloroacetate (DCA)and tyrosine catabolism. The hypothesis is that tyrosine metabolism will be greatest in subject who harbor the KRT variant for GSTz1/MAAI for which DCA exhibits a high Km.

Specific Aim 4. Quantify the effects of DCA on human tyrosine metabolism and on its own biotransformation in relation to dose and genotype.

Inclusion Criteria:

• Adults scheduled for elective surgery for benign liver disease.
• Normal EKG and history
• Normal baseline labs

Exclusion Criteria:

• Pregnancy
• severe anemia, defined as a hematocrit < 30%.
• diabetes mellitus
• renal insufficiency, defined as a serum creatinine > 1.5 mg/dl or a creatinine clearance < 60 ml/min
• elevated liver enzymes
• psychiatric illness requiring medication
• primary biliary cirrhosis or any other form of cirrhosis
• viral hepatitis or non-viral steatohepatitis
• coronary heart disease, defined as requiring daily administration of anti-anginal drugs or as New York Heart Association Class III or IV heart failure
• malignancy of any type in any anatomical location