d-Limonene Induced Hyaline Droplet Nephropathy in α2u-Globulin Transgenic Mice
| Autor: | Douglas Caudill, Lois D. Lehman-McKeeman |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Genetically modified mouse medicine.medical_specialty Pathology Metabolite Blotting Western Mice Transgenic Biology Toxicology Nephrotoxicity Nephropathy Mice chemistry.chemical_compound Internal medicine Alpha-Globulins Cyclohexenes medicine Animals Hyaline Kidney Terpenes medicine.disease Rats Inbred F344 Rats Mice Inbred C57BL Blot Endocrinology medicine.anatomical_structure chemistry Toxicity Kidney Diseases Limonene |
| Zdroj: | Toxicological Sciences. 23:562-568 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/23.4.562 |
| Popis: | d-Limonene Induced Hyaline Droplet Nephropathy in α2u-Globulin Transgenic Mice. Lehmian-McKeeman, L. D., and Caudill, D. (1994). Fundam. Appl. Toxicol. 23, 562-568. d-Limonene is a hyaline droplet inducing agent and produces nephrotoxicity in male rats when the 1,2 epoxide metabolite binds to α2u-globulin. Mice, which do not synthesize α2u-globulin, are resistant to hyaline droplet nephropathy. In this study, the ability of d -limonene to cause hyaline droplet nephropathy in a transgenic mouse engineered to express α2u-globulin was evaluated. The C57BL/6 derived mice excreted 0.4 ± 0.1 mg α2u-globulin/day, or approximately 16 mg α2u-globulin/kg body wt. This represents about 30% or the amount excreted by adult male rats (11.9 ± 1.1 mg/day or approximately 48 mg/kg). Transgenic mice excreted less mouse urinary protein (9.3 ± 1.2 mg/day) than normal mice (15.1± 1.6 mg/day). Unlike normal male rats, untreated transgenic mice did not show significant spontaneous hyaline droplet formation. Liver microsomes from naive transgenic mice oxidized d -limonene to the cis- and trans-isomers of the 1,2-epoxide, and following oral treatment with [14C]d-limonene reversible binding of d-limonene equivalents to renal cytosolic proteins was observed. Furthermore, with d -limonene treatment, hyaline droplets were observed in the transgenic mouse kidneys. These droplets, however, were much smaller in size than those seen in d-limonene-treated male rats. The accumulation of α2u-globulin in the kidneys of transgenic mice and normal male rats before and after d-limonene treatment was analyzed by Western blotting. These results indicated that α2u-globulin was present in the kidneys of the control transgenic mice, despite the lack of spontaneous hyaline droplet formation. After d-limonene treatment, approximately a threefold increase in α2u-globulin in the transgenic mouse kidney was observed, a response similar in magnitude to that seen in d-limonene-treated male rats. These results indicate that expression of α2u-globulin in a species that does not normally develop hyaline droplet nephropathy is necessary and sufficient to render that species sensitive to this renal toxicity. |
| Databáze: | OpenAIRE |
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