Induction of bladder lesion by terephthalic acid and its mechanism.
OBJECTIVE
To provide more information for rational evaluation of potential risks of terephthalic acid (TPA), we studied the effects of TPA on rats' bladders in 90 days after TPA exposure.


METHODS
Sprague Dawley rats were subdivided into five groups, ingesting 0%, 0.04%, 0.2%, 1%, and 5% TPA respectively for a sub-chronic feeding study lasting for 90 days. Urine, serum and samples of brain, liver, lung, kidney, bladder, etc. were collected and analyzed.


RESULTS
TPA ingesting decreased the value of urinary pH, and increased the contents of Ca2+, Zn2+, Mg2+, Na+, K+ in urine. The volume of 24 h urine was significantly increased in male rats in the 1% and 5% TPA groups. Urinary white sediment was found in both sexes, and its formation in male rats seemed more susceptible than that in female rats. Alpha 2u-globulin (AUG) in serum and urine of male rats was markedly increased in a dose-dependent manner. Fifteen cases of hyperplasia (simple or atypical) were determined in the 5% TPA ingesting group, 14/52 in male rats and 1/23 in female rats. Among them 3 male rats had no stone or calculus. Those with either bladder stones or hyperplasia were accompanied with urinary white sediments.


CONCLUSIONS
White sediment accompanied with elevated urine AUG is the basis of TPA induced urolith formation, and is also associated with TPA induced bladder epithelial cell proliferation. It can act as an early biomarker for the potential toxic effect of TPA.
Dai
Gui-Dong
GD
Institute of Toxicology, Nanjing Medical University, Jiangsu, China. daiguidong@163.com
Cui
Lun-Biao
LB
Song
Ling
L
Zhao
Ren-Zhen
RZ
Cheng
Jian-Feng
JF
Liu
Mei-Xia
MX
Zhou
Jian-Wei
JW
Xiao
Hang
H
Wang
Xin-Ru
XR
D000510:Alpha-Globulins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced*; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001744:Urinary Bladder Calculi / Q000139:chemically induced*
D000510:Alpha-Globulins; D015415:Biomarkers; D010795:Phthalic Acids; C013803:alpha 2u globulin; C011363:terephthalic acid