Serum chemistry marker

Serum chemistry markers play an important role in hepatotoxicity evaluation in human and animal safety studies. The classic markers of hepatotoxicity are alanine aminotransferase (ALT), aspartate aminotrasnferase (AST) and alkaline phosphatase (ALP) [124—127]. Drug-induced hepatotoxicity can be difficult to assess in some circumstances. Hepatotoxic responses can be intrinsic (predictable, dose-related) or idiosyncratic (unpredictable, non-dose-related). ALT, AST and ALP are generally not useful for predicting idiosyncratic responses. The administration of some drugs, such as isoniazid, can lead to a high incidence of ALT elevation, but are tolerated by most patients without severe hepatotoxicity. Adverse drug reactions can be masked... 

Essential pretreatment investigations include cross-sectional imaging with CT or MRI, serum chemistry, and tumor markers. 18FDG PET maybe a useful adjunct to determine the site of treatment failure in the presence of hepatic and extrahepatic disease, to rectify the inability to follow tumor markers, and to account for, or clarify the presence of, discordant post-treatment findings on CT and/or MRI. 

Blood analysis was only carried out in dogs and rabbits, exposed to either dose of SM. There were no effects on RBC count, total and differential WBC counts, haematocrit or haemoglobin. There were also no changes in blood clinical chemistry markers including total protein, urea, serum glutamic pyruvic transaminase, lactic dehydrogenase, alkaline phosphatase, creatinine, bilirubin, sodium chloride, potassium and carbon dioxide. 

Soimenschein C, Soto AM, Eemandez ME, et al. 1995. Development of a marker of estrogenic exposure in human serum. Clinical Chemistry 41(12 Suppl) 1888-1895. 

The first four materials (IRMM/IFCC-452, 453, 454, 455) are expected to be released during 2000. Projects on the certification of reference materials for cardiac marker (myoglobin) and total protein concentration in serum are under discussion. Even so the number of available CRMs for clinical chemistry and occupational toxicology is still limited. This has to do with the complexity of physiological compounds (e.g. proteins), the instabihty (e.g. enzymes), or the volatility (e.g. solvents). 

Leucine aminopeptidase preferentially hydrolyses peptide bonds adjacent to an Al-terminal residue that carries a large hydrophilic side chain, in particular a leucyl residue. Commonly used synthetic substrates are leucinamide, leucine 4-nitroanilide and leucine hydrazide. This cytosolic zinc-metalloenzyme has been identified in virtually all animal tissues, and most studies have been performed on the enzyme (Mj 324,000) from bovine lens, which has been crystallized. It consists of 6 identical subunits (M, 54,000 487 amino acids 2 Zrf per subunit), and its catalytically active site is in the C-terminal domain. The enzyme is present in many other cells and tissues, e.g. lung, stomach, kidney intestine, serum and leukocytes. In clinical chemistry, this enzyme is a marker for hepatic cell lysis, and may even be a more sensitive marker for acute hepatitis than the aminotransferases. 

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