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Uroprotective effect of ambroxol in cyclophosphamide-induced cystitis in mice

  • Urology - Original Paper
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Abstract

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.

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Acknowledgements

This study was supported by the Scientific Research Project Coordination Unit of Karadeniz Technical University (Grant Number: THD-2018-7356). The authors are grateful to Asst. Prof. Mahmoud Abudayyak for helping to determine the antioxidant assays.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey

    Elif Nur Barut & Seckin Engin

  2. Deparment of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey

    Burak Barut & Arzu Ozel

  3. Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Cansu Kaya & Gokcen Kerimoglu

  4. Drug and Pharmaceutical Technology Application and Research Center, Karadeniz Technical University, Trabzon, Turkey

    Arzu Ozel

  5. Faculty of Medicine, Department of Pharmacology, Karadeniz Technical University, 61080, Trabzon, Turkey

    Mine Kadioglu

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  1. Elif Nur Barut
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Correspondence to Mine Kadioglu.

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Ethical approval

The experimental protocols were approved by Karadeniz Technical University the Institutional Animal Ethical Committee (2016/29). All animal studies were performed according to the Guide for the Care and Use of Laboratory Animals.

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Barut, E.N., Engin, S., Barut, B. et al. Uroprotective effect of ambroxol in cyclophosphamide-induced cystitis in mice. Int Urol Nephrol 51, 803–810 (2019). https://doi.org/10.1007/s11255-019-02128-y

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  • DOI: https://doi.org/10.1007/s11255-019-02128-y

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