Nrf2 Pathway Ameliorates Bladder Dysfunction in Cyclophosphamide‐Induced Cystitis via Suppression of Oxidative Stress

Abstract

Objective. To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC). Methods. We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway. Results. After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2-/- CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2+/+ CYP mice, while there were no significant changes in the Nrf2-/- CYP mice. Conclusion. Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.

β-Caryophyllene Ameliorates Cyclophosphamide Induced Cardiac Injury: The Association of TLR4/NFκB and Nrf2/HO1/NQO1 Pathways

“…Nrf2 not only mediates an effect in the cardiac tissue only, but also in other organs. For instance, the Nrf2 pathway ameliorated bladder dysfunction in cyclophosphamide-induced cystitis through oxidative stress suppression [ 43 ].…”

Cannabidiol as a Promising Therapeutic Option in IC/BPS: In Vitro Evaluation of Its Protective Effects against Inflammation and Oxidative Stress

“…Given that the production of ROS is central to the progression of many inflammatory diseases [27] and has already been identified as an important underlying feature in IC/BPS pathobiology [28,84,85], we herein evaluated the effects of TNFα on the production of ROS and how this is affected by concomitant treatment with CBD. The production and maintenance of controlled levels of intracellular ROS are critical for cells to perform a number of physiological functions, including maintenance of redox homeostasis, cell cycle signaling, and hormone production [86].…”

“…Nrf2 was recently identified as one of the contributors to IC/BPS by Ni et al [85]. They showed that nrf2 knockout mice with an experimentally induced cystitis developed more severe symptoms of IC/BPS and bladder injury with structural destruction of the urothelium compared to wild type mice [85].…”

“…Nrf2 was recently identified as one of the contributors to IC/BPS by Ni et al [85]. They showed that nrf2 knockout mice with an experimentally induced cystitis developed more severe symptoms of IC/BPS and bladder injury with structural destruction of the urothelium compared to wild type mice [85]. In addition, D'Amico et al [94] have shown that the use of bioactive olive oil compounds to treat mice with induced cystitis reduces bladder damage and oxidative stress by upregulating the Nrf2/HO1 pathway, restoring levels of antioxidant enzymes, and reducing lipid myeloperoxidation in the bladders [103].…”

[8] and [10]-Gingerol reduces urothelial damage in ifosfamide-induced hemorrhagic cystitis via JAK/STAT/FOXO signaling pathway via IL-10

“…NrF-2 diminishes bladder dysfunction through suppressing oxidative stress 31 . Ni, et al 32 showed that NrF-2 knockout mice presented more severe symptoms of cystitis after cyclophosphamide administration, followed by a decrease in SOD-1 activity and increase in mRNA expression of HO-1 and NQO-1. mRNA expression of HO-1 and NQO-1 after IFO-induced cystitis was also described by Kim, et al 33 .…”