title: Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model.
abstract: Ischemia-reperfusion (IR) has been reported to be associated with augmented reactive oxygen radicals and cytokines. Currently, we aimed to examine the influence of fluoxetine, which is already used as a preoperative anxiolytic, in the context of IR induced by occlusion of infrarenal abdominal aorta (60 min of ischemia) and its effects on renal oxidative status, inflammation, renal function, and cellular integrity in reperfusion (120 min post-ischemia). Male rats were randomly assigned as control, IR, and pretreated groups. The pretreated group animals received fluoxetine (20 mg/kg, i.p.) once daily for 3 days. Renal tissue oxidative stress, myeloperoxidase activity, proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6), histology, and function were assessed. As an anti-inflammatory cytokine, interleukin-10 was also assessed. IR led to a significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant antioxidant balance and decrease in superoxide dismutase activity and ferric reducing/antioxidant power level (p < 0.05), but fluoxetine was able to restore these parameters. High concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase activity caused by IR were significantly decreased in kidney tissue with fluoxetine. In addition, interleukin-10 levels were high in fluoxetine pretreated group. IR resulted in disrupted cellular integrity, infiltration of tissue with leukocytes, and decreased serum creatinine-urea levels (p < 0.05). Fluoxetine significantly restored impaired redox balance and inflammation parameters of rats subjected to IR to baseline values. This beneficial effect of fluoxetine on redox balance might be addressed to an improvement in renal function.
authors.affiliation: Department of Biology, Science Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Aksu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Guner
authors.forename: Onur M
authors.initials: OM
authors.lastname: Yaman
authors.forename: Hayriye
authors.initials: H
authors.lastname: Erman
authors.forename: Duygu
authors.initials: D
authors.lastname: Uzun
authors.forename: Meliha
authors.initials: M
authors.lastname: Sengezer-Inceli
authors.forename: Ahmet
authors.initials: A
authors.lastname: Sahin
authors.forename: Nermin
authors.initials: N
authors.lastname: Yelmen
authors.forename: Remisa
authors.initials: R
authors.lastname: Gelisgen
authors.forename: Hafize
authors.initials: H
authors.lastname: Uzun
authors.forename: Gulderen
authors.initials: G
authors.lastname: Sahin
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D005473:Fluoxetine; D009195:Peroxidase