title: Effect of hyperbaric oxygen on cyclosporine-induced nephrotoxicity and oxidative stress in rats.
abstract: Reactive oxygen species have been suggested to be involved in cyclosporine nephrotoxicity. Hyperbaric oxygen is known to induce the generation of reactive oxygen species in tissues. The aim of this study was to investigate whether the use of hyperbaric oxygen concurrently with cyclosporine potentiates cyclosporine nephrotoxicity by inducing oxidative stress in kidneys. The study consisted of four groups of rats: a control group, a cyclosporine group (15 mg/kg/day intraperitoneally for 14 days), a hyperbaric oxygen group (60 min. every day for five days at 2.5 atmosphere absolute), and a cyclosporine + hyperbaric oxygen group (cyclosporine 15 mg/kg/day intraperitoneally for 14 days + hyperbaric oxygen for 60 min at 2.5 atmosphere absolute every day for five days on the last five days of cyclosporine treatment). Oxidative stress was determined by measuring renal thiobarbituric acid-reactive substances content, renal superoxide dismutase, and glutathione peroxidase activities. Cyclosporine increased serum urea and creatinine levels, indicating the development of nephrotoxicity, and induced significant oxidative stress in rat kidneys. Hyperbaric oxygen alone did not alter any of the biochemical and oxidative stress parameters compared to the control group. When used concurrently with cyclosporine, hyperbaric oxygen significantly reduced cyclosporine-induced oxidative stress, but it neither attenuated nor aggravated cyclosporine-induced nephrotoxicity. These results suggest that reactive oxygen species are involved in cyclosporine nephrotoxicity, but are not the direct cause of the toxicity. Although concurrent use of cyclosporine and hyperbaric oxygen did not exacerbate cyclosporine nephrotoxicity in this model, we recommend that the renal functions of patients be monitored periodically when these treatments are used concurrently.
authors.affiliation: Department of Undersea and Hyperbaric Medicine, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Uskudar, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Ay
authors.forename: Gunalp
authors.initials: G
authors.lastname: Uzun
authors.forename: Yalcin
authors.initials: Y
authors.lastname: Onem
authors.forename: Secil
authors.initials: S
authors.lastname: Aydinoz
authors.forename: Senol
authors.initials: S
authors.lastname: Yildiz
authors.forename: Oguz
authors.initials: O
authors.lastname: Bilgi
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal
authors.forename: Enes Murat
authors.initials: EM
authors.lastname: Atasoyu
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D004357:Drug Synergism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006931:Hyperbaric Oxygenation; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007677:Kidney Function Tests; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances
chemical_list: D007166:Immunosuppressive Agents; D017392:Thiobarbituric Acid Reactive Substances; D016572:Cyclosporine; D005979:Glutathione Peroxidase