title: In vivo prevention of bladder urotoxicity: purified hydroxytyrosol ameliorates urotoxic effects of cyclophosphamide and buthionine sulfoximine in mice.
abstract: Urotoxicity is a troublesome complication associated with cyclophosphamide (CP) and L-buthionine-SR-sulfoximine (BSO) treatment in chemotherapy. With this concern in mind, the present study investigated the potential effects of a hydroxytyrosol extract from olive mill waste (OMW) on urotoxicity induced by acute CP and BSO doses using a Swiss albino mouse model. Toxicity modulation was evaluated by measuring lipid peroxidation (LPO) and antioxidants in urinary bladder. The findings revealed that the hydroxytyrosol extract exerted a protective effect not only on LPO but also on enzymatic antioxidants. When compared to the controls, the CP-treated animals underwent significant decreases in the glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP), and catalase (CAT) activities. The level of glutathione (GSH) was also reduced with increased doses of LPO in the CP-treated animals. L-Buthionine-SR-sulfoximine treatment exerted an additive toxic effect on the CP-treated animals. Interestingly, pretreatment with the hydroxytyrosol extract restored the activities of all enzymes back to normal levels and exhibited an overall protective effect on the CP- and BSO-induced toxicities in urinary bladder. The restoration of GSH through the treatment with the hydroxytyrosol extract can play an important role in reversing CP-induced apoptosis and free radical-mediated LPO.
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, University of El-Manar I, Tunis, Tunisia. rouissik2000@yahoo.fr
authors.forename: Kamel
authors.initials: K
authors.lastname: Rouissi
authors.forename: Bechr
authors.initials: B
authors.lastname: Hamrita
authors.forename: Soumaya
authors.initials: S
authors.lastname: Kouidi
authors.forename: Yosra
authors.initials: Y
authors.lastname: Messai
authors.forename: Bassem
authors.initials: B
authors.lastname: Jaouadi
authors.forename: Khaled
authors.initials: K
authors.lastname: Hamden
authors.forename: Imen
authors.initials: I
authors.lastname: Medimegh
authors.forename: Slah
authors.initials: S
authors.lastname: Ouerhani
authors.forename: Mohamed
authors.initials: M
authors.lastname: Cherif
authors.forename: Amel Benammar
authors.initials: AB
authors.lastname: Elgaaied
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000633:toxicity*; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007220:Industrial Waste / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D031658:Olea / Q000737:chemistry; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D007220:Industrial Waste; D010936:Plant Extracts; C005975:3,4-dihydroxyphenylethanol; D019328:Buthionine Sulfoximine; D003520:Cyclophosphamide; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D010626:Phenylethyl Alcohol