Preservation of uroplakins by 2-mercaptoethanesulfonate in cyclophosphamide-induced rat cystitis.
Cyclophosphamide (CP) causes extensive cystitis, which is ameliorated with concomitant treatment with mesna. We investigated the protective mechanisms of mesna in the expression of uroplakin (UP), a strong mucosal barrier against toxic materials, in CP-induced rat cystitis. A total of 54 SD female rats received a single intraperitoneal injection of 200 mg of CP/kg. Six CP-treated, 6 CP + mesna (120 mg/kg)-treated rats, and 6 negative controls were sequentially sacrificed at 12, 24, and 72 h post-CP injection. The bladders were harvested. The levels of UPIa, Ib, II, and III mRNA on real-time PCR, the UPII and III expressions on immunoblotting, and the UPII expression on immunolocalization study in the harvested bladder were maximally suppressed within 12-24 h, whereas partially or completely recovered at 24-72 h post-CP injection. In addition, the responses in UPs after a CP insult were heterogeneous (i.e., markedly suppressed in UPII and lesser destructive in UPIII). Even though the mesna-treated rats also showed transient and small reductions in the mRNA levels of all UPs, mesna clearly preserved the UP expressions of mRNA and protein in CP-induced urinary bladder mucosa. In conclusion, this study suggests that CP transiently reduces the expression of UPs and mesna protects the urinary bladder mucosa through the preservation of UPs protein.
Kyung
Yoon Soo
YS
Department of Urology, Dankook University College of Medicine, Ansedong Cheonan Si, Chungcheoung Nam Do, South Korea.
Park
Hee Yoon
HY
Lee
Gilho
G
D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced*; D005260:Female; D007274:Injections, Intraperitoneal; D008562:Membrane Glycoproteins / Q000378:metabolism*; D015080:Mesna / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
D008562:Membrane Glycoproteins; D003520:Cyclophosphamide; D015080:Mesna