Methyl isobutyl ketone (MIBK) induction of α2u-globulin nephropathy in male, but not female rats
| Autor: | N.M. Berdasco, R. Gingell, S. Green, G.C. Hard, Susan J. Borghoff, W. Gulledge |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Administration Oral Toxicology Nephropathy Proliferating Cell Nuclear Antigen Internal medicine Alpha-Globulins medicine Animals Alpha globulin Hyaline Cell Proliferation Kidney biology Cell growth Methyl n-Butyl Ketone Organ Size medicine.disease Immunohistochemistry Rats Inbred F344 Rats Proliferating cell nuclear antigen Endocrinology medicine.anatomical_structure biology.protein Female Kidney Diseases Corn oil Kidney disease |
| Zdroj: | Toxicology. 258:131-138 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/j.tox.2009.01.018 |
| Popis: | Male F-344 rats were administered corn oil (vehicle control), d-limonene (positive control, 300mg/kg), or MIBK (1000mg/kg) and female F-344 rats corn oil (vehicle control) or MIBK for 10 consecutive days by oral gavage. Approximately 24h after the final dose the kidneys were excised and the left kidney prepared and evaluated for histological changes including protein (hyaline) droplet accumulation, immunohistochemical staining for alpha2u-globulin (alpha2u), and proliferating cell nuclear antigen (PCNA) to quantitate renal cell proliferation. The right kidney was prepared for quantitation of total protein and alpha2u using an ELISA. MIBK elicited an increase in protein droplets, accumulation of alpha2u, and renal cell proliferation in male, but not female rats, responses characteristic of alpha2u-mediated nephropathy. MIBK produced identical histopathological changes in the male rat kidney when compared to d-limonene, an acknowledged inducer of alpha2u-nephropathy except that the grade of severity tended to be slightly lower with MIBK. MIBK did not induce any effects in female rats. Therefore, renal histopathology, along with the other measures of alpha2u accumulation, provides additional weight of evidence to support the inclusion of MIBK in the category of chemicals exerting renal effects through a alpha2u-nephropathy-mediated mode-of-action. |
| Databáze: | OpenAIRE |
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