The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide‐Induced Cystitis in Rats

Abstract

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats.

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

“…The metabolic conversion of CYP into toxic metabolites is associated with ROS production resulting in oxidative stress, lipid peroxidation, and oxidative cell damage (Mohammad et al, 2012). In animal models of CYP--induced urinary bladder injury, several studies have shown that animals injected with CYP exhibited elevated levels of bladder lipid peroxidation (LPO) and reduced levels of bladder GSH (Arafa, 2009;Bhatia et al, 2008;Sakthivel and Guruvayoorappan, 2015), glutathione-S-transferase (GST) (Arafa, 2009), GR, GP, CAT and SOD (Bhatia et al, 2008;Kim et al, 2014), along with increased levels of bladder MDA and NO in both bladder and serum (Al-Yahya et al, 2009;Arafa, 2009;Kim et al, 2014;Moraes et al, 2013). These results are attributed to the toxic metabolite of CYP acrolein which led to NO overproduction, and lipid peroxide formation.…”

“…It has been reported that CYP-induces a marked rise in levels of CCL11 in serum, and urinary bladder protein and mRNA expression (Abdi et al, 2018). However, a notable increase in the bladder MPO which is correlated with leukocyte infiltration in the urothelium has been documented following CYP administration (Moraes et al, 2013).…”

“…Furthermore, the Caesalpinia pyramidalis Tul. (F: Fabaceae), a Brazilian tree and its inner bark extract possesse anti-inflammatory and antioxidant properties, as well as having the capability of reducing the bladder damage occurring in models of CYP-induced urotoxicity through marked reduction of bladder MPO content (Moraes et al, 2013). Moreover, the food coloring and spice agent curcumin has pharmacological properties including antioxidant and anti-inflammatory effects, which was evidenced by the marked reduction of bladder MPO level following CYP (Arafa, 2009).…”

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

“…In recent years, alternative medicine has been used to treat many diseases by utilizing antioxidants from herbal agents 18 . In this regard, a number of researches have demonstrated that extracts or isolated compounds of medicinal plants can reduce cystitis and treat CYP-related HC 7,19,20 , as well as nephrotoxicity [20][21][22] . The aerial parts of HT with methanolic extract possesses high antioxidant activities 23 which might be useful in protecting against or decelerating the development of diverse oxidative stress-induced disorders 24 .…”

Traditional use, phytochemistry and biological activities of Poincianella pyramidalys (Tul.) LP Queiroz

“…The groups treated with the extract (100 and 400 mg kg -1 ) showed a significant reduction of cyclophosphamide-induced MPO. 100 mg kg -1 concentration was significantly decreased in leukocyte infiltration in the urinary bladder and basal concentration of MDA (Moraes et al, 2013). Santana et al (2012) evaluated the anti-inflammatory activity of ethanolic extract of P. pyramidalis in acute pancreatitis model in rats.…”