alpha sub(2u)-Globulins in the urine of male rats: A reliable indicator for alpha sub(2u)-globulin accumulation in the kidney

Increases in kidney-type- alpha sub(2u)-globulin ( alpha G-K, molecular weight approximately 16 kDa) were detected in the urine of male adult rats treated with d-limonene by immunoblotting analysis using an antiserum which distinguishes native-type- alpha sub(2u)-globulin ( alpha G-N, molecular weig...

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Published in:Toxicology (Amsterdam) 1996-01, Vol.106 (1-3), p.149-157
Main Authors: Saito, K, Uwagawa, S, Kaneko, H, Shiba, K, Tomigahara, Y, Nakatsuka, I
Format: Article
Language:English
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Summary:Increases in kidney-type- alpha sub(2u)-globulin ( alpha G-K, molecular weight approximately 16 kDa) were detected in the urine of male adult rats treated with d-limonene by immunoblotting analysis using an antiserum which distinguishes native-type- alpha sub(2u)-globulin ( alpha G-N, molecular weight approximately 19 kDa) from alpha G-K. When male adult rats received d-limonene by gavage (0-300 mg/kg/day) for 14 consecutive days, dose-dependent increases in urinary excretion of alpha G-K were observed at a dosage level of more than 30 mg/kg/day. This was found to be directly correlated with alterations in the concentration of renal alpha G-K as well as the accumulation of hyaline droplets in proximal convoluted tubule (PCT) epithelial cells in the kidneys. Marked elevation of urinary alpha G-K was also noted following oral treatment of adult male rats with 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), decalin and isophorone (ISP) by gavage (1.5 mmol/kg/day) for 7 consecutive days, again in association with increased concentrations of renal alpha G-K and hyaline droplet accumulation in renal PCT epithelial cells. However, no such increases in urinary alpha G-K were observed for male adult rats treated with nephrotoxic chemicals such as puromycin aminonucleoside (PAN) (15 mg/kg/day, s.c., 14 consecutive days) or hexachloro-1,3-butadiene (HCBD) (100 mg/kg/day, p.o., 5 consecutive days), lacking the ability to cause kidney accumulation of the hyaline droplets and alpha G-K. The findings in this study thus indicate that measurement of urinary alpha G-K can give reliable estimates not only of the potential to cause renal accumulation of alpha sub(2u)-globulin but also of its magnitude.
ISSN:0300-483X