Protein urinary biomarkers

Between 2008 and 2010, the FDA (2008), the EMA (2008), and the PMDA (2010) qualified the use of seven urinary biomarkers for GLP rat studies to support the safe conduct of early-phase clinical trials KlM-1, CLU, TFF-3, p2-microglobulin, CysC, albumin, and total protein. These are detailed below. 

Horiuchi et al., 2000 Japanese postmenopause n = 85 Women with a high soy protein intake showed less bone loss and higher BMD at the lumbar spine Biomarkers urinary deoxypyridinoline (bone resorption) decreased... 

Biomarkers for decreased function include increases in urinary proteins and elevation of serum creatinine or 2-microglobulin. Biomarkers for renal cytotoxicity include increases in urinary excretion of antigens and enzymes located within renal tissues. Biomarkers for biochemical changes occurring within the kidneys include eicosanoids, fibronectin, kallikrein activity, and glycosaminoglycans in urine. 

Analysis of Blood Samples. Urinary metabolites undergo relatively rapid elimination from the body, whereas blood components offer biomarkers that have the potential to be used for verification of sulfur mustard exposure long after the exposure incident. Three different approaches have been used for blood biomarker analysis. The intact macromolecule such as protein or DNA with the sulfur mustard adducts still attached can be analyzed. To date, this approach has only been demonstrated for hemoglobin using in vitro experiments. For proteins, an alternate approach is to enzymatically digest them to produce a smaller peptide with the sulfur mustard adduct still attached. Methods of this type have been developed for both hemoglobin and albumin. A third approach has been to cleave the sulfur mustard adduct from the macromolecule and analyze in a fashion similar to that used for free metabolites found in the urine. The later two approaches have both been successfully used to verify human exposure of sulfur mustard. 

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