Enzymatic Methods Used for Diagnosis

Amador, Elías; Wacker, Warren E. C.

doi:10.1002/9780470110317.ch6

Cited by 28 publications

(2 citation statements)

References 218 publications

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“…Glutamic-oxaloacetic transaminase (GOT) activity was also measured as an index of more general toxic effects on such organs as heart, muscle, and spleen. 25 Compound 5a did not induce signs of liver or kidney damage, as demonstrated by unchanged hepatic and renal glutathione levels (Fig. 5A) and plasma GPT and GOT concentrations (Fig.…”

Section: Resultsmentioning

confidence: 88%

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Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs

Vaccarino

Paúl

Mukherjee

et al. 2007

Bioorganic & Medicinal Chemistry

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Abstract-A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic.

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Section: Resultsmentioning

confidence: 88%

“…Serum transaminase activity. 19,25 Twenty-four hours after drug treatment, mice were decapitated and blood withdrawn into 1-cc heparinized syringes. Plasma was obtained by centrifugation of blood samples at 3000 rpm for 10 min at 4°C.…”

Section: 34mentioning

confidence: 99%