Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species

Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β)). In the animal model, 14-week-old conscious Wistar–Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1β in conscious rats.

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Action of chondroitin sulfate on the level of cytokines and reactive oxygen species in blood serum upon carrageenan-induced inflammation

Bulletin of Taras Shevchenko National University of Kyiv Series Problems of Physiological Functions Regulation ◽

10.17721/2616_6410.2017.22.9-11 ◽

2017 ◽

Vol 22 (1) ◽

pp. 9-11

Author(s):

K. Dvorshchenko ◽

M. Ashpin ◽

O. Korotkyi ◽

Ye. Torgalo ◽

T. Falalyeyeva

Keyword(s):

Reactive Oxygen Species ◽

Blood Serum ◽

Chondroitin Sulfate ◽

Inflammatory Cytokines ◽

Superoxide Radical ◽

Reactive Oxygen ◽

Oxygen Species ◽

Tnf Α ◽

Rat Paw ◽

Pro Inflammatory Cytokines

Increase of concentration of pro-inflammatory cytokines (IL-1β, TNF-α) is fixed in blood serum at carrageenan-induced rat paw inflammation, as well as increase of the content of reactive oxygen species (superoxide radical, hydrogen peroxide). At introduction of the preparation on the basis of chondroitin sulfate the level of pro-inflammatory cytokines and reactive oxygen species in blood serum decreases, while the concentration of IL10 increases in 1,7 times concerning the group of animals with сarrageenan-induced inflammation.

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Pinellia ternata lectin exerts a pro-inflammatory effect on macrophages by inducing the release of pro-inflammatory cytokines, the activation of the nuclear factor-κB signaling pathway and the overproduction of reactive oxygen species

International Journal of Molecular Medicine ◽

10.3892/ijmm.2015.2315 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1127-1135 ◽

Cited By ~ 13

Author(s):

HONG-LI YU ◽

TENG-FEI ZHAO ◽

HAO WU ◽

YAO-ZONG PAN ◽

QIAN ZHANG ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Reactive Oxygen ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Oxygen Species ◽

Pinellia Ternata ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

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Regulation of multiple transcription factors by reactive oxygen species and effects of pro-inflammatory cytokines released during myocardial infarction on cardiac differentiation of embryonic stem cells

International Journal of Cardiology ◽

10.1016/j.ijcard.2013.04.178 ◽

2013 ◽

Vol 168 (4) ◽

pp. 3458-3472 ◽

Cited By ~ 13

Author(s):

Sau Kwan Law ◽

Cecilia Sze-Lee Leung ◽

Ka Long Yau ◽

Chi Lok Tse ◽

Chun Kit Wong ◽

...

Keyword(s):

Myocardial Infarction ◽

Reactive Oxygen Species ◽

Stem Cells ◽

Transcription Factors ◽

Embryonic Stem Cells ◽

Inflammatory Cytokines ◽

Embryonic Stem ◽

Cardiac Differentiation ◽

Oxygen Species ◽

Pro Inflammatory Cytokines

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P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0527a ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Dan Li ◽

Chenyu Li ◽

Yan Xu

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Tnf Α ◽

Public Dataset ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine ◽

Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

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Intracellular Reactive Oxygen Species Mediate the Therapeutic Effect of Induced Pluripotent Stem Cells for Acute Kidney Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1609638 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Shun Wang ◽

Xiaoyu Tian ◽

Yijun Li ◽

Rong Xue ◽

Haochen Guan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Acute Kidney Injury ◽

Therapeutic Effect ◽

Pluripotent Stem Cells ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Oxygen Species ◽

Renal Ischemia Reperfusion Injury ◽

Induced Pluripotent

Aims. Treatment for acute kidney injury (AKI) is challenging. Induced pluripotent stem cells (iPSCs) have great therapeutic potential. This study sought to determine whether iPSCs attenuate AKI and the role of reactive oxygen species (ROS). Results. We intravenously injected isogenic iPSCs into mice 2 h after renal ischemia-reperfusion injury (IRI). The cells were selectively trafficked to ischemia/reperfusion-injured kidney where they decreased kidney ROS and inflammatory cytokines and improved kidney function and morphology. Pretreating the cells with ROS inhibitors before administration decreased iPSC engraftment and abolished the protective effect of iPSCs. In contrast, pretreating iPSCs with hydrogen peroxide increased iPSC engraftment and therapeutic effect. Although the intravenously administered iPSCs trafficked to the IRI kidney, the cells did not differentiate into proximal or distal tubular epithelial cells. In vitro, the capabilities of the iPSC-released substances to promote proliferation and decrease apoptosis of renal epithelial cells were increased by ROS pretreatment of iPSCs. Moreover, pretreatment of the iPSCs with ROS inhibitor had the opposite effect. Similarly, moderate concentrations of ROS increased while ROS inhibitors decreased iPSC mobility, adhesion to the extracellular matrix, and mitochondrial metabolism. Innovation and Conclusion. iPSCs decreased renal ischemia/reperfusion injury mainly through iPSC-released substances. The therapeutic effect, mitochondrial metabolism, mobility, and kidney trafficking of iPSCs were ROS dependent.

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