Home
Resources
Publications
Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium

Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium

Francis M Hughes Jr, Alexa G Corn, Andrew R Nimmich, Jeffery D Pratt-Thomas, J Todd Purves

Adv Biosci Biotechnol. 2013 Aug;4(88):10.4236/abb.2013.48A2002.

PMID: 24353901

Abstract:

Purpose:
Hemorrhagic cystitis (HC or bladder inflammation) affects a significant number of patients undergoing cyclophosphamide (CP) chemotherapy despite treatment with 2-mercaptoethane sulfonate (Mesna) to inactivate the metabolite acrolein. While the mechanism is unknown, there is clearly acrolein-independent damage to the urothelium. In this study we have explored the induction of apoptosis in the urothelium as a marker of damage and the mechanism underlying the acrolein-independent apoptosis.
Materials and methods:
Apoptosis in urothelium (caspase-3/7 activity and Poly (ADP-ribosyl) polymerase (PARP) cleavage) was measured following CP administration (80 mg/kg). Sodium 2-mercaptoethane sulfonate (Mesna) was used to mask acrolein's effect. An IL-1β receptor antagonist and a cell-permeable caspase-1 inhibitor were used to assess the involvement of IL-1β and caspase-1, respectively.
Results:
Two waves of apoptosis were detected following CP administration, one peaking at 2 h and a second at 48 h. The first wave was independent of acrolein. Caspase-1 was also active at 2 h and activation of caspase-3/7 was blocked by a caspase-1 inhibitor but not an IL-1β receptor antagonist suggesting the direct activation of caspase-3/7 by caspase-1 without the need for IL-1β as an intermediate.
Conclusions:
Our results indicate that CP initiates an early, acrolein-independent wave of apoptosis that results from direct cleavage of caspase-3/7 by caspase-1.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415323	Caspase-1 Inhibitor I, Cell-Permeable			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: