title: Uroprotective effect of oleuropein in a rat model of hemorrhagic cystitis.
abstract: Hemorrhagic cystitis is one of the devastating complications seen after receiving cyclophosphamide chemotherapy. Oleuropein is the most important phenolic compound of olive leaves that mediates most of its beneficial pharmacological properties. Herein, we investigated the possible uroprotective effect of oleuropein against cyclophosphamide induced hemorrhagic cystitis in a rat model. For this purpose, we measured bladder nitric oxide, reduced glutathione, catalase, tumor necrosis factor-alpha and vascular endothelial growth factor levels in addition to the bladder gene expression of intercellular adhesion molecule-1 after induction of hemorrhagic cystitis in the presence or absence of oleuropein. Histopathological examination of bladder tissues was also performed. After cyclophosphamide injection, we demonstrated a significant decrease in bladder reduced glutathione (39%) and catalase (55.4%) levels and a significant increase of nitric oxide (5.6 folds), tumor necrosis factor-alpha (3.3 folds), vascular endothelial growth factor (2 folds) and intercellular adhesion molecule-1 (8 folds) bladder contents when compared to those in normal control rats. Administration of oleuropein induced a marked elevation in bladder reduced glutathione (37.8%), catalase (100.4%) with a prominent reduction of bladder nitric oxide (40%), tumor necrosis factor-alpha (35.9%) and vascular endothelial growth factor (56.2%) levels along with downregulation of intercellular adhesion molecule-1 bladder expression (73.1%) in comparison to cyclophosphamide treated rats levels. Our data demonstrated that oleuropein counteracts the harmful effects of cyclophosphamide on the bladder through its antioxidant and anti-inflammatory activities. Oleuropein exerts a definite uroprotective effect against cyclophosphamide induced hemorrhagic cystitis in rats.
authors.affiliation: Emergency Hospital, Biochemistry Department, Mansoura University, Mansoura 35516, Egypt; Pharmaceutical Sciences Department, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia. Electronic address: emyosh@yahoo.com.
authors.forename: Iman O
authors.initials: IO
authors.lastname: Sherif
authors.affiliation: Urology Department, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia.
authors.forename: Ziad M
authors.initials: ZM
authors.lastname: Nakshabandi
authors.affiliation: Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mie A
authors.initials: MA
authors.lastname: Mohamed
authors.affiliation: Urology Department, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Osama M
authors.initials: OM
authors.lastname: Sarhan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D001743:Urinary Bladder / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D057888:Iridoid Glucosides; D039823:Iridoids; D018799:Intercellular Adhesion Molecule-1; C002769:oleuropein; D003520:Cyclophosphamide
keywords: Cyclophosphamide; Hemorrhagic cystitis; Intercellular adhesion molecule-1 (ICAM-1); Oleuropein; Tumor necrosis factor (TNF)-α; Vascular endothelial growth factor (VEGF)