Uroprotective effect of ambroxol in cyclophosphamide-induced cystitis in mice

Int Urol Nephrol. 2019 May;51(5):803-810. doi: 10.1007/s11255-019-02128-y. Epub 2019 Mar 20.


Purpose: Hemorrhagic cystitis (HC) is defined as any types of acute or chronic inflammation of urinary bladder with several reasons. One of the most common causes of HC is cyclophosphamide (CYP), an effective antineoplastic agent, due to its urotoxic potential. Ambroxol (AMB) is a mucoactive drug that has been used for numerous respiratory diseases. Besides its mucolytic activity, AMB is a potent antioxidant and antiinflammatory agent that is becoming more attractive for the treatment of several oxidative/inflammatory disorders. The aim of this study was to evaluate the uroprotective potential of AMB in CYP-induced HC.

Method: Male Balb/c mice were pretreated with AMB (30, 70, and 100 mg/kg) once a day for 3 consecutive days before HC induction with CYP (300 mg/kg). Mesna (30 mg/kg;i.p.), only drug in the management of CYP-induced HC, was administered 20 min before; 4 and 8 h after cystitis induction. The urinary bladders were harvested and evaluated in functional, biochemical, and histological studies.

Results: CYP-induced HC markedly reduced acetylcholine (ACh)-induced contractions in detrusor strips and AMB at 100 mg/kg caused a significant increase in the responsiveness to ACh. Pretreatment with AMB prevented the elevation of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) level, reduction of total glutathione (GSH) that induced by CYP. However, treatment with AMB did not improve the bladder weight and some histological parameters.

Conclusion: These results suggest that AMB pretreatment could improve CYP-induced HC via antioxidant and antiinflammatory activities.

Keywords: Ambroxol; Antiinflammatory; Antioxidant; Cylophosphamide; Cystitis; Mesna.

MeSH terms

  • Ambroxol / therapeutic use*
  • Animals
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Cyclophosphamide / adverse effects*
  • Cystitis / chemically induced*
  • Cystitis / prevention & control*
  • Hemorrhage / chemically induced*
  • Hemorrhage / prevention & control*
  • Male
  • Mice
  • Mice, Inbred BALB C


  • Antineoplastic Agents, Alkylating
  • Ambroxol
  • Cyclophosphamide