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Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model

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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.

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Conflict of interest

All authors have disclosed potential conflicts of interest and all authors have read the journal’s policy on conflicts of interest and have none to declare. AS is a Ph.D. student at Istanbul University, Cerrahpasa Medical School, and no financial benefit was provided by Asfarma, International Pharmaceutical Marketing Company.

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Authors and Affiliations

  1. Department of Biology, Science Faculty, Istanbul University, Istanbul, Turkey

    Ugur Aksu & Meliha Sengezer-Inceli

  2. Department of Physiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    Ibrahim Guner, Onur M. Yaman, Nermin Yelmen & Gulderen Sahin

  3. Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    Hayriye Erman, Remisa Gelisgen & Hafize Uzun

  4. Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    Duygu Uzun

  5. Asfarma, International Pharmaceutical Marketing, Istanbul, Turkey

    Ahmet Sahin

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  1. Ugur Aksu
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  2. Ibrahim Guner
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  3. Onur M. Yaman
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Correspondence to Gulderen Sahin.

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Aksu, U., Guner, I., Yaman, O.M. et al. Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model. J Physiol Biochem 70, 925–934 (2014). https://doi.org/10.1007/s13105-014-0361-0

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  • DOI: https://doi.org/10.1007/s13105-014-0361-0

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