ALPHA(2U)-GLOBULINS IN THE URINE OF MALE-RATS - A RELIABLE INDICATOR FOR ALPHA(2U)-GLOBULIN ACCUMULATION IN THE KIDNEY

Increases in kidney-type-alpha(2n)-globulin (alpha G-K, molecular weig ht 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(2n)-globulin (alpha G-N, molecu lar 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 day s, dose-dependent increases in urinary excretion of alpha G-K were obs erved at a dosage level of more than 30 mg/kg/day. This was found to b e directly correlated with alterations in the concentration of renal a lpha G-K as well as the accumulation of hyaline droplets in proximal c onvoluted tubule (PCT) epithelial cells in the kidneys. Marked elevati on of urinary alpha C-K was also noted following oral treatment of adu lt male rats with 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (D CB), decalin and isophorone (ISP) by gavage (1.5 mmol/kg/day) for 7 co nsecutive days, again in association with increased concentrations of renal alpha G-K and hyaline droplet accumulation in renal PCT epitheli al cells. However, no such increases in urinary alpha G-K were observe d for male adult rats treated with nephrotoxic chemicals such as purom ycin aminonucleoside (PAN) (15 mg/kg/day, s.c., 14 consecutive days) o r 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 a reliable estimates not on ly of the potential to cause renal accumulation of alpha(2n)-globulin but also of its magnitude.