title: Protective effects of doxycycline in ischemia/reperfusion injury on kidney.
abstract: Renal ischemia and reperfusion injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. The aim of this study was to evaluate whether doxycycline, a member of the tetracycline family of antibiotics, protects kidney tissue or not. 36 Sprague-Dawley rats (200-250 g) were used. The animals were divided into three groups: control, ischemia/reperfusion and ischemia/reperfusion+doxycycline group. Rats were subjected to renal ischemia by clamping the left pedicle for 1 h, and then reperfused for 1 h. The ischemia/reperfusion+doxycycline group were pretreated intraperitoneally with doxycycline suspension (10 mg/kg) 2 h before the induction of ischemia. Our results indicate that malondialdehyde, matrix-metalloproteinase-2, interleukin-2, interleukin-6, interleukin-10, interleukin 1-beta and tumor necrosis factor-alpha levels were significantly higher in the ischemia/reperfusion group than those in the control group. Doxycycline administration significantly decreased these parameters. Tissue inhibitor of metalloproteinases-1 levels also increased after ischemia/reperfusion and decreased with doxycycline pretreatment, but these changes were not significantly different. Glutathione levels significantly decreased after ischemia/reperfusion injury when compared with the control group and doxycycline pretreatment significantly increased glutathione levels when compared with the ischemia/reperfusion group. Apoptotic cells and p53 positive cells were significantly decreased in doxycycline treated group. These results suggest that doxycycline reduces renal oxidative injury and facilitates repair. Doxycycline may play a role in a renoprotective therapeutic regimen.
authors.affiliation: Dumlupinar University, Medical Faculty, Physiology Department, Kutahya, Turkey. kucukaysegul@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Kucuk
authors.forename: S
authors.initials: S
authors.lastname: Kabadere
authors.forename: M
authors.initials: M
authors.lastname: Tosun
authors.forename: T
authors.initials: T
authors.lastname: Koken
authors.forename: M K
authors.initials: MK
authors.lastname: Kinaci
authors.forename: B
authors.initials: B
authors.lastname: Isikli
authors.forename: N
authors.initials: N
authors.lastname: Erkasap
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004318:Doxycycline / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000517:prevention & control*; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016753:Interleukin-10; D008315:Malondialdehyde; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020778:Matrix Metalloproteinase 2; D005978:Glutathione; D004318:Doxycycline