Fosaprepitant improves cyclophosphamide-induced bladder damage by alleviating inflammatory response in mice

Area of Science:

• Pharmacology
• Urology
• Immunology

Background:

• Interstitial cystitis (IC) involves significant inflammation, making anti-inflammatory strategies crucial for treatment.
• Neurokinin 1 receptor (NK1R) antagonists show promise in managing inflammatory conditions.
• Cyclophosphamide (CP)-induced cystitis serves as a relevant preclinical model for studying IC.

Purpose of the Study:

• To investigate the protective effects of fosaprepitant (FOS), an NK1R antagonist, against cyclophosphamide (CP)-induced cystitis.
• To evaluate FOS's impact on detrusor contractility, vascular permeability, and inflammatory markers in a mouse model of bladder inflammation.

Main Methods:

• A mouse model of cystitis was induced using multiple injections of cyclophosphamide (CP).
• Mice received varying doses of fosaprepitant (FOS) intraperitoneally for seven consecutive days.
• Evaluated parameters included detrusor muscle contractility, bladder vascular permeability, myeloperoxidase (MPO) activity, and Toll-like receptor 4 (TLR4) pathway expression.

Main Results:

• FOS treatment significantly attenuated the increased detrusor contractility observed in CP-induced cystitis.
• FOS administration restored impaired bladder vascular permeability and markedly suppressed elevated MPO activity in bladder tissue.
• FOS treatment significantly decreased TLR4 expression, indicating an anti-inflammatory effect by inhibiting key inflammatory pathways.

Conclusions:

• Fosaprepitant demonstrates significant protective effects in a preclinical model of interstitial cystitis.
• FOS ameliorates detrusor overactivity and reduces inflammation by inhibiting MPO activity and TLR4 expression.
• These findings suggest FOS holds potential as a therapeutic agent for managing interstitial cystitis and related inflammatory bladder conditions.