Hydrogen Sulfide Attenuates LPS‐Induced Acute Kidney Injury by Inhibiting Inflammation and Oxidative Stress

Chen, Yuhong; Jin, Sheng; Teng, Xu; Hu, Zhenjie; Zhang, Zhihong; Qiu, Xuan; Tian, Danyang; Wu, Yuming

doi:10.1155/2018/6717212

Cited by 118 publications

(113 citation statements)

References 38 publications

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“…Male wild-type C57BL6 mice, 6-8 weeks old, weighing 20 to 25 g, taken from the River of Life laboratory in Beijing, were kept at constant temperature and humidity (22 ± 1°C and 50 ± 10%, respectively) and under a 12 h light/dark cycle in a laboratory animal care facility with free access to food and water. TheS-AKI mouse model was constructed by an intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS, E. coli O111: B4, Sigma, USA) according to previous reports [16]. Mdivi-1 (Sigma, USA) was properly dissolved in dimethyl sulfoxide (DMSO) and administered intraperitoneally at a dose of 3 mg/kg one hour before LPS injection.…”

Section: Methodsmentioning

confidence: 99%

An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

Liu

Wang

et al. 2020

BioMed Research International

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Mitochondria play an essential role in energy metabolism. Oxygen deprivation can poison cells and generate a chain reaction due to the free radical release. In patients with sepsis, the kidneys tend to be the organ primarily affected and the proximal renal tubules are highly susceptible to energy metabolism imbalances. Dynamin-related protein 1 (DRP1) is an essential regulator of mitochondrial fission. Few studies have confirmed the role and mechanism of DRP1 in acute kidney injury (AKI) caused by sepsis. We established animal and cell sepsis-induced AKI (S-AKI) models to keep DRP1 expression high. We found that Mdivi-1, a DRP1 inhibitor, can reduce the activation of the NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis pathway and improve mitochondrial function. Both S-AKI models showed that Mdivi-1 was able to prevent the mitochondrial content release and decrease the expression of NLRP3 inflammasome-related proteins. In addition, silencing NLRP3 gene expression further emphasized the pyroptosis importance in S-AKI occurrence. Our results indicate that the possible mechanism of action of Mdivi-1 is to inhibit mitochondrial fission and protect mitochondrial function, thereby reducing pyroptosis. These data can provide a potential theoretical basis for Mdivi-1 potential use in the S-AKI prevention.

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Section: Methodsmentioning

confidence: 99%

An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

Liu

Wang

et al. 2020

BioMed Research International

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“…Acute kidney injury has an occurrence of 30–40% in intensive care unit patients ( Hoste et al, 2015 ), and one of its main causes is the endotoxemia promoted by LPS, a naturally found component present in the outer membrane of most gram-negative bacteria, which can trigger cytokine secretion and a systemic inflammatory process ( Chen et al, 2018 ). Organ impairment by our AKI model was confirmed by increased blood urea and creatinine levels, as well as increased gene expression of well-described AKI markers: NGAL and Kim-1 ( Mishra et al, 2004 ; Han et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…With respect to sepsis and endotoxemia models, both are known to be associated with the generation of reactive oxygen species (ROS) and oxidant injury, responses that are normally present in AKI ( Chen et al, 2018 ; Gu et al, 2019 ). We measured the activity of enzymes related to oxidative stress and the GSH levels, and we found a decrease in reduced GSH in both LPS groups.…”

Section: Discussionmentioning

confidence: 99%

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Physical Exercise Exacerbates Acute Kidney Injury Induced by LPS via Toll-Like Receptor 4

et al. 2020

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Introduction: Lipopolysaccharide (LPS) is a systemic response-triggering endotoxin, which has the kidney as one of its first targets, thus causing acute injuries to this organ. Physical exercise is capable of promoting physiological alterations and modulating inflammatory responses in the infectious process through multiple parameters, including the toll-like receptor (TLR)-4 pathway, which is the main LPS signaling in sepsis. Additionally, previous studies have shown that physical exercise can be both a protector factor and an aggravating factor for some kidney diseases. This study aims at analyzing whether physical exercise before the induction of LPS endotoxemia can protect kidneys from acute kidney injury. Methods: C57BL/6J male mice, 12 weeks old, were distributed into four groups: (1) sedentary (control, N = 7); (2) sedentary + LPS ( N = 7); (3) trained ( N = 7); and (4) trained + LPS ( N = 7). In the training groups, the animals exercised 5×/week in a treadmill, 60 min/day, for 4 weeks (60% of max. velocity). Sepsis was induced in the training group by the application of a single dose of LPS (5 mg/kg i.p.). Sedentary animals received LPS on the same day, and the non-LPS groups received a saline solution instead. All animals were euthanized 24 h after the administration of LPS or saline. Results: The groups receiving LPS presented a significant increase in serum urea ( p < 0.0001) and creatinine ( p < 0.001) concentration and renal gene expression of inflammatory markers, such as tumor necrosis factor alpha and interleukin-6, as well as TLRs. In addition, LPS promoted a decrease in reduced glutathione. Compared to the sedentary + LPS group, trained + LPS showed overexpression of a gene related to kidney injury (NGAL, p < 0.01) and the protein levels of LPS receptor TLR-4 ( p < 0.01). Trained + LPS animals showed an expansion of the tubulointerstitial space in the kidney ( p < 0.05) and a decrease in the gene expression of hepatic AOAH ( p < 0.01), an enzyme involved in LPS clearance. Conclusion: In contrast to our hypothesis, training was unable to mitigate the renal inflammatory response caused by LPS. On the contrary, it seems to enhance injury by accentuating endotoxin-induced TLR-4 signaling. This effect could be partly due to the modulation of a hepatic enzyme that detoxifies LPS.

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“…Многочисленные исследования показали, что сульфид водорода (H 2 S) может быть включен в терапию септического шока, оказывая потенциальное воздействие на ишемию/реперфузионное повреждение во многих органах и метаболические заболевания путем ингибирования воспаления и окислительного стресса [1,6,71]. Сероводород синтезируется из L-цистеина аминокислоты через витамин-B6-зависимую цистатионин-β-синтазу или цистатионин-γлиазу.…”

Section: сульфид водорода (H 2 S)unclassified

Septic shock: perspective methods of diagnostics and therapy based on immunopathogenesis

Гоманова

2020

Med. immunol.

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Based on the III International Consensus on the definition of Sepsis and Septic Shock (Sepsis-3), the modern definition of septic shock was proposed: “Septic shock is a type of sepsis that is accompanied by severe hemodynamic, metabolic and cellular disorders, and these disorders are associated with a higher risk fatal outcome”. Despite the classic idea of septic shock development (proinflammatory, immunosuppressive phases and, finally, multiple organ failure with distinct shock organs), the theory of activation of the caspase, endocannabioid system and system of protein of programmed death-1 in evolving septic shock are promising approaches to development of new diagnostic and therapeutic methods. Lymphopenia is already observed at an early stage of septic shock, which further leads to deep immunosuppression. Previous experimental studies have revealed some treatment methods to reduce the pro-inflammatory stage, which, however, did not show desired results in clinics. Now it is necessary to look for ways to inhibit apoptosis, depletion of lymphocytes, macrophages and other immune cells in the course of septic shock. It is known that caspases mediate innate detection of pathogenic microorganisms, cause pyroptosis, activation of monocytes. It has been proven that inhibition of caspase-8, caspase-11 leads to decreased monocyte functioning and cytokine release, which plays an important role in immunopathogenesis of septic shock. Associations of PD-1 and PD-2 expression on CD4+ lymphocytes and monocytes are also shown to be connected with immune dysfunctions, decrease in lymphocyte proliferation, and increased interleukin-10 concentration. Stimulation of the cannabinoid receptors is able to reduce inflammation by inhibiting cytopathic and immunosuppressive effects of pathogens. It has been shown that classic septic shock biomarkers (pro-inflammatory, anti-inflammatory cytokines; procalcitonin, lactate, etc.) do not have predictive power in relation to the outcome of the disease. Circulating and citrullated histones, determined by mass spectrometry, may serve as potential diagnostic markers of septic shock, but they require further study. Use of oxidized phospholipid oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphocholine), hydrogen sulfide and Fasciola hepatica fatty acid binding proteins (hepatic fluke) prevents oxidative stress, synthesis of pro-inflammatory cytokines and provides maturation of macrophages and dendritic cells. Further study of immunological reactions during septic shock is of great importance for substantiation of new approaches to the diagnostics and therapy of septic shock.

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Hydrogen Sulfide Attenuates LPS‐Induced Acute Kidney Injury by Inhibiting Inflammation and Oxidative Stress

Cited by 118 publications

References 38 publications

An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

Physical Exercise Exacerbates Acute Kidney Injury Induced by LPS via Toll-Like Receptor 4

Septic shock: perspective methods of diagnostics and therapy based on immunopathogenesis

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