UNLABELLED: Acetaminophen (APAP) OTC regimen is not compatible with kidney and liver toxic effects. In order to further understand the determinism of the repair process, we have studied the expression of some target extracellular matrix proteoglycan components in an animal model. MATERIALS AND METHODS: An acute APAP toxic dose (800 mg/bw) was administered to 45 mice aged 1 month. At 24 hours, tissue samples were processed for light microscopy, electromicroscopy and RT-PCR analysis. RESULTS: Extensive necrotic lesions involving hepatocytes and tubular epithelial cells associate strong positivity for proteoglycans, detected as convoluted filaments with lateral projections, frequently associated with collagen fibers, cell surface and other matrix components. Overexpression for perlecan, syndecan 1 and 4 and low expression for biglycan was assessed by RT-PCR. CONCLUSIONS: Extracellular matrix and cell surface components are early involved in both lesional mechanism and repair reaction post acetaminophen injury.
UNLABELLED: Acetaminophen (APAP) OTC regimen is not compatible with kidney and liver toxic effects. In order to further understand the determinism of the repair process, we have studied the expression of some target extracellular matrix proteoglycan components in an animal model. MATERIALS AND METHODS: An acute APAP toxic dose (800 mg/bw) was administered to 45 mice aged 1 month. At 24 hours, tissue samples were processed for light microscopy, electromicroscopy and RT-PCR analysis. RESULTS: Extensive necrotic lesions involving hepatocytes and tubular epithelial cells associate strong positivity for proteoglycans, detected as convoluted filaments with lateral projections, frequently associated with collagen fibers, cell surface and other matrix components. Overexpression for perlecan, syndecan 1 and 4 and low expression for biglycan was assessed by RT-PCR. CONCLUSIONS: Extracellular matrix and cell surface components are early involved in both lesional mechanism and repair reaction post acetaminophen injury.
Authors: Carol R Gardner; Joshua P Gray; Laurie B Joseph; Jessica Cervelli; Nicole Bremer; Yunjung Kim; Vladimir Mishin; Jeffrey D Laskin; Debra L Laskin Journal: Toxicol Appl Pharmacol Date: 2010-01-25 Impact factor: 4.219