title: Oral glutamine attenuates cyclophosphamide-induced oxidative stress in the bladder but does not prevent hemorrhagic cystitis in rats.
abstract: Cyclophosphamide (CP) is widely used in the treatment of cancer and non-malignant disease states such as rheumatoid arthritis. Hemorrhagic cystitis is a major dose-limiting side effect of CP. The incidence of this side effect is related to the dosage and can be as high as 75%. Elimination of the side effects of CP can lead to better tolerance of the drug, and a more efficient therapy can be achieved for patients in need of CP treatment. Several studies have demonstrated that oxidative stress and neutrophil infiltration play important roles in CP-induced bladder damage. Glutamine is utilized under clinical conditions for preventing chemotherapeutic drug-induced side effects, based on its ability to attenuate oxidative stress. The aim of the study is to verify whether glutamine prevents CP-induced oxidative stress and bladder damage using a rat model. Adult male rats were administered 150 mg/kg body weight of CP intraperitoneally. Glutamine pretreated rats were administered 1 g/kg body weight of glutamine orally 2 h before the administration of CP. Vehicle/glutamine-treated rats served as controls. All the rats were killed 16 h after the dose of CP/vehicle. The urinary bladders were removed and used for light microscopic and biochemical studies. The markers of oxidative stress including malondialdehyde content, protein carbonyl content, protein thiol, and myeloperoxidase activity, a marker of neutrophil infiltration, were measured in bladder homogenates. CP treatment induced hemorrhagic cystitis in the rats. Pretreatment with glutamine significantly reduced CP-induced lipid peroxidation (p < 0.01), protein oxidation (p < 0.01), and increase in myeloperoxidase activity (p < 0.05). However, it did not prevent CP-induced bladder damage. The results of the present study show that glutamine pretreatment does not attenuate CP-induced hemorrhagic cystitis, although it prevents CP-induced oxidative stress and neutrophil infiltration significantly. It is therefore necessary to clarify the utility of glutamine as a chemoprotective agent before it is recommended in the market as a nutrient supplement.
authors.affiliation: Department of Biochemistry, Christian Medical College, Bagayam, Vellore, 632002, Tamil Nadu, India. premilaabraham@yahoo.com
authors.forename: Premila
authors.initials: P
authors.lastname: Abraham
authors.forename: Bina
authors.initials: B
authors.lastname: Isaac
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Ramamoorthy
authors.forename: Kasthuri
authors.initials: K
authors.lastname: Natarajan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005973:Glutamine / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005973:Glutamine; D008315:Malondialdehyde; D003520:Cyclophosphamide