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. 2018 Apr 3;32(8):4408–4419. doi: 10.1096/fj.201701415R

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© The Author(s)

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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H-IPSE mitigates ifosfamide-induced histopathological changes in the bladder. Histologic assessment of bladders from mice receiving the following: saline only (A), ifosfamide only (B), MESNA and ifosfamide (C), recombinant IL-4 and ifosfamide (D), H-IPSE and ifosfamide (E), and H-IPSE + neutralizing anti-IL-4 antibody and ifosfamide (F). Bladders from the saline-treated group showed normal urothelium with no sign of edema (ed) or urothelial denudation (ud). Ifosfamide-injected bladders exhibited segmental urothelial denudation, severe edema with effacement of the submucosa and occasional frank hemorrhage. Ifosfamide-injured bladders exposed to H-IPSE, IL-4, or MESNA showed intact urothelium and overall preserved bladder architecture with a relative lack of edema. The protective effect of H-IPSE was reversed by prior administration of neutralizing anti-IL-4 antibody.