Chemico-biological interactions
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Chem. Biol. Interact. · Apr 2013
Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia and urinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis.
The aim of this study was to investigate the involvement of the transient receptor potential ankyrin 1 (TRPA1) in haemorrhagic cystitis, the main side effect of cyclophosphamide-based chemotherapy. Hannover female rats received intraperitoneal (i.p.) injection of cyclophosphamide (three doses of 100 mg/kg, every other day, in a total of five days). This treatment was followed by the treatment with TRPA1 antagonist HC 030031 (50 mg/kg, p.o.). ⋯ The treatment with HC 030031 either before (100 mg/kg, p.o.) or after (30 mg/kg, i.v.) cyclophosphamide inhibited the non-voiding contractions but failed to counteract the loss in voiding efficiency. Our data demonstrates that nociceptive symptoms and urinary bladder overactivity caused by cyclophosphamide, in part, are dependent upon the activation of TRPA1. In this context, the antagonism of the receptor may be an alternative to minimise the urotoxic symptoms caused by this chemotherapeutic agent.