α2 u-Globulins in the urine of male rats: a reliable indicator for α2 u-globulin accumulation in the kidney

• Published in: Toxicology (Amsterdam) 1996-01, Vol.106 (1), p.149-157
• Main Authors: Saito, Koichi, Uwagawa, Satoshi, Kaneko, Hideo, Shiba, Kunio, Tomigahara, Yoshitaka, Nakatsuka, Iwao
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Hyaline droplet; Indicator; Medical sciences; Nephrotoxicity; Plant poisons toxicology; Toxicology; α2 u-Globulin; α2 u-Globulin nephropathy
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/0300-483X(95)03176-G

Increases in kidney-type- α 2 u -globulin (αG-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- α 2 u -globulin (αG-N, molecular weight approximately 19 kDa) from aG-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 αG-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 αG-K as well as the accumulation of hyaline droplets in proximal convoluted tubule (PCT) epithelial cells in the kidneys. Marked elevation of urinary αG-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 αG-K and hyaline droplet accumulation in renal PCT epithelial cells. However, no such increases in urinary αG-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 αG-K. The findings in this study thus indicate that measurement of urinary αG-K can give a reliable estimates not only of the potential to cause renal accumulation of α 2 u -globulin but also of its magnitude.