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 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 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 a reliable estimates not only of the potential to cause renal accumulation of alpha 2u-globulin but also of its magnitude.
Saito
K
K
Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd., Osaka, Japan.
Uwagawa
S
S
Kaneko
H
H
Shiba
K
K
Tomigahara
Y
Y
Nakatsuka
I
I
D000284:Administration, Oral; D000510:Alpha-Globulins / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine*; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D002070:Butadienes / Q000633:toxicity; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D000077222:Limonene; D008297:Male; D008969:Molecular Sequence Data; D011691:Puromycin / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000008:administration & dosage / Q000633:toxicity
D000510:Alpha-Globulins; D000900:Anti-Bacterial Agents; D002070:Butadienes; D002273:Carcinogens; D053138:Cyclohexenes; D013729:Terpenes; C013803:alpha 2u globulin; D011691:Puromycin; D000077222:Limonene; C001335:hexachlorobutadiene