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.

Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: a possible role for the regulation of TLR4/MyD88/NF-κB signaling pathway

“…TNF-α was also reported as an upstream regulator for MMP-9 [43]. In our study, we found that fluoxetine downregulated these inflammatory cytokines, which is in accordance with previous studies [44, 45]. TLRs belong to a large family of pattern recognition receptors that play a key role in innate immunity and inflammatory responses.…”

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis

“…First, the activation of TNF-α, IL-1β and IL-6 could promote the synthesis of leukocytes and release superoxide and proteolytic enzymes to result in loss of cellular integrity [35]. On the other hand, increased ECM expression induced by IL-6 in turn result in glomerular hypertrophy and narrowing renal tubular lumen [34,36].…”

Effect of Fluoxetine on Periodontal Status in Patients With Depression: A Cross‐Sectional Observational Study

“…Thus, the influence of depression cannot be considered to be responsible for this observation. The second possibility suggests the pleiotropic anti‐inflammatory, 22,41 antioxidative, 42 and anticollegenolytic 22 properties of fluoxetine contributing toward better periodontal health in patients receiving this medication. This explanation seems credible in light of the demonstration of downregulation of the matrix metalloproteinase (MMP) level by fluoxetine in the studies by Li et al, 21 Benekareddy et al, 43 and Branco‐de‐Almeida 22 .…”