Acacia Senegal Gum Exudate Offers Protection Against Cyclophosphamide‐Induced Urinary Bladder Cytotoxicity

Abstract

Cylophosphamide (CYCL) is a strong anticancer and immunosuppressive agent but its urotoxicity presents one of the major toxic effects that limit its wide usage particularly in high dose regimens. Therefore, this study aimed to investigate Acacia Senegal gum exudate, Gum Arabic (GA), for its possible role as a natural, nontoxic agent against CYCL-induced urotoxicity. Male Swiss albino rats were exposed to CYCL (150 mg/kg BW, once i.p) with or without GA oral supplementation (7.5 g/kg/day for 6 days) through drinking water. Glutathione (GSH), Malondialdehyde (MDA) and Nitric oxide (NO) bladder contents were assessed. Responsiveness of the bladder rings to acetylcholine (ACh) in vitro, microscopic and macroscopic features are also investigated. CYCL produced pronounced harmful effects on bladder urothelial lining with significant increases in (MDA) and NO levels in the tissue homogenates. Bladder-GSH content is dropped by over 60% following CYCL injection. Bladder contractility, as measured by its responsiveness to ACh, recorded a marked reduction. The isolated bladders exhibited such macroscopic changes as severe edema, inflammation and extravasation. The bladder weight increased as well. Histological changes were evident in the form of severe congestion, petechial hemorrhage and chronic inflammatory reaction in the lamina propria accompanied with desquamated epithelia. GA, a potential protective agent, produced an almost complete reversal of NO induction, lipid peroxidation or cellular GSH bladder contents in the GA + CYCL-treated group. Likewise, bladder inflammation and edema were reduced. Bladder rings showed a remarkable recovery in their responsiveness to ACh. Bladder histological examination showed a near normal configuration and structural integrity, with a significant reduction in inflammation and disappearance of focal erosions. These remarkable effects of GA may be attributed to its ability to neutralize acrolein, the reactive metabolite of CYCL and/or the resultant reactive oxygen metabolites, through a scavenging action. GA may limit the cascading events of CYCL-induced damage, initiating a cytoprotective effect leading to structural and functional recovery of the bladder tissues.

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna

“…Acrolein causes the depletion of cellular antioxidant nucleophiles, such as glutathione, and it initiates the lipid peroxidation that results in HC [39]. Scientists have demonstrated a severe depletion in cellular GSH content in urinary bladder homogenates of CPtreated groups [25,40]. IFO caused significant reductions in GSH levels both in kidney and bladder, when compared Images presented in column A were stained with HxE.…”

Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats

“…On the other hand, the increase in MDA and NO(x) levels along with the decreased GSH contents, might be due to the ability of acrolein to deprive the cell of its natural defense (GSH) against the ROS (Al-Yahya et al, 2009) or to the direct conjugation of CP and its metabolites with free or protein bound SH groups (Yousefipour et al, 2005), stimulating the formation of free radicals thereby interfering with the antioxidant functions (Al-Yahya et al, 2009;Tsakadze et al, 2003).…”

“…It is also used to treat some non-cancerous conditions (Al-Yahya et al, 2009). CP used in regimen prior to stem cell transplantation and in low doses in the treatment of several autoimmune diseases (Luznik and Fuchs, 2010).…”

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

“…[192021] In an actively sensitized animal model, Zhu et al . [9] demonstrated that nebulized ketamine decreased IL-4 and NO levels and the expression of i-NOS in the inflamed airways and, as a result, ketamin-attenuated airway hyperresponsiveness and inflammation in experimental asthma.…”