Ozone therapy ameliorates tubulointerstitial inflammation by regulating TLR4 in adenine-induced CKD rats

Chen, Zhiyuan; Liu, Xiuheng; Yu, Gang; Chen, Hui; Wang, Lei; Wang, Zhishun; Qiu, Tao; Wang, Xiaodong

doi:10.3109/0886022x.2016.1143757

Cited by 19 publications

(8 citation statements)

References 33 publications

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“…TLR4, as the promoter of a signaling pathway, activates nuclear factor-κB (NF-κB) and stimulates pro-inflammatory responses. Some studies have revealed that the knockdown of the TLR4 significantly reduces the risk of fibrosis [37]. Renal fibrosis could be effectively ameliorated through inhibition of the NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Ameliorates Renal Interstitial Fibrosis by Inhibiting the TLR4/NF-κB and MAPK Signaling Pathways

Guo

Zhang

et al. 2019

IJMS

123

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Salidroside (Sal) is an active ingredient that is isolated from Rhodiola rosea, which has been reported to have anti-inflammatory activities and a renal protective effect. However, the role of Sal on renal fibrosis has not yet been elucidated. Here, the purpose of the current study is to test the protective effects of Sal against renal interstitial fibrosis (RIF), and to explore the underlying mechanisms using both in vivo and in vitro models. In this study, we establish the unilateral ureteric obstruction (UUO) or folic acid (FA)-induced mice renal interstitial fibrosis in vivo and the transforming growth factor (TGF)-β1-stimulated human proximal tubular epithelial cell (HK-2) model in vitro. The levels of kidney functional parameters and inflammatory cytokines in serum are examined. The degree of renal damage and fibrosis is determined by histological assessment. Immunohistochemistry and western blotting are used to determine the mechanisms of Sal against RIF. Our results show that treatment with Sal can ameliorate tubular injury and deposition of the extracellular matrix (ECM) components (including collagen Ш and collagen I). Furthermore, Sal administration significantly suppresses epithelial-mesenchymal transition (EMT), as evidenced by a decreased expression of α-SMA, vimentin, TGF-β1, snail, slug, and a largely restored expression of E-cadherin. Additionally, Sal also reduces the levels of serum biochemical markers (serum creatinine, Scr; blood urea nitrogen, BUN; and uric acid, UA) and decreases the release of inflammatory cytokines (IL-1β, IL-6, TNF-α). Further study revealed that the effect of Sal on renal interstitial fibrosis is associated with the lower expression of TLR4, p-IκBα, p-NF-κB and mitogen-activated protein kinases (MAPK), both in vivo and in vitro. In conclusion, Sal treatment improves kidney function, ameliorates the deposition of the ECM components and relieves the protein levels of EMT markers in mouse kidneys and HK-2 cells. Furthermore, Sal treatment significantly decreases the release of inflammatory cytokines and inhibits the TLR4/NF-κB and MAPK signaling pathways. Collectively, these results suggest that the administration of Sal could be a novel therapeutic strategy in treating renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Salidroside Ameliorates Renal Interstitial Fibrosis by Inhibiting the TLR4/NF-κB and MAPK Signaling Pathways

Guo

Zhang

et al. 2019

IJMS

123

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“…Inhibition of NF-κB, a molecule involved in the TNFα/Tnfr1 cascade, by pyrrolidine dithiocarbamate also attenuated AdCKD progression 9 . Ozone therapy attenuated AdCKD by decreasing the expression of toll-like receptor 4 (TLR4) 10 , a lipopolysaccharide (LPS) receptor. Endoplasmic reticulum (ER) stress was also elevated in the kidneys of AdCKD mice, although this was reduced by the fatty acid receptor GPR40 agonist and aggravated in GPR40 knockout mice 11 .…”

Section: Introductionmentioning

confidence: 99%

Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression

Ōshima

Wakino

Kanda

et al. 2023

Sci Rep

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Sodium benzoate (SB), a known D-amino acid oxidase (DAO) enzyme inhibitor, has an anti-inflammatory effect, although its role in renal damage has not been explored. 2,8-dihydroxyadenine crystal induced chronic kidney disease, in which TNF-α is involved in the pathogenesis, was established by oral adenine administration in C57BL/6JJcl mice (AdCKD) with or without SB to investigate its renal protective effects. SB significantly attenuated AdCKD by decreasing serum creatinine and urea nitrogen levels, and kidney interstitial fibrosis and tubular atrophy scores. The survival of AdCKD mice improved 2.6-fold by SB administration. SB significantly decreased the number of infiltrating macrophages observed in the positive F4/80 immunohistochemistry area and reduced the expression of macrophage markers and inflammatory genes, including TNF-α, in the kidneys of AdCKD. Human THP-1 cells stimulated with either lipopolysaccharide or TNF-α showed increased expression of inflammatory genes, although this was significantly reduced by SB, confirming the anti-inflammatory effects of SB. SB exhibited renal protective effects in AdCKD in DAO enzyme deficient mice, suggesting that anti-inflammatory effect of SB was independent of DAO enzyme activity. Moreover, binding to motif DNA sequence, protein level, and mRNA level of NF-κB RelB were significantly inhibited by SB in AdCKD kidneys and lipopolysaccharide treated THP-1 cells, respectively. We report that anti-inflammatory property of SB is independent of DAO enzymatic activity and is associated with down regulated NF-κB RelB as well as its downstream inflammatory genes such as TNF-α in AdCKD.

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“…Although the exact mechanism of action of ozonated autohemotherapy is less well characterized, amelioration of inflammation and tissue damage could play critical roles. 9,10 Furthermore, ozonated autohemotherapy is not only a safe procedure without reperfusion damage but also a much more economical and practical treatment, and this may, thus, benefit the global COVID-19 patient population with refractory hypoxemia.…”

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confidence: 99%

Recovery of Four COVID-19 Patients via Ozonated Autohemotherapy

Tan

Heng

et al. 2020

The Innovation

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We report a case series of ozonated autohemotherapy of four COVID-19 patients, classified as critically ill (1 patient), severe (1 patient), and moderate (2 patients). Each ozonated autohemotherapy treatment was performed at a concentration of 40 μg/ml of ozone per 100 ml of blood. The number of treatments varied from 1 to 9 depending on the disease severity. All 4 patients, including 1 critically ill patient with severe acute respiratory distress syndrome (ARDS) and life-threatening refractory hypoxemia, recovered uneventfully and were discharged from the hospital after viral clearance. The younger sibling of the critically ill patient was also diagnosed with COVID-19 and developed ARDS with hypoxemia, who received mechanical ventilation through an endotracheal tube and extracorporeal membrane oxygenation (ECMO) support. The overall medical cost for 18 days spent in the intensive care unit (ICU) and 56 days of hospitalization was $139,935 USD. On the other hand, our critically ill patient underwent 9 ozonated autohemotherapy treatments and spent 10 days in the ICU and was discharged on hospital day 30; his hospitalization cost amounted to $15,466.50 USD. This case series suggests that ozonated autohemotherapy may be an alternative noninvasive medical treatment for COVID-19 patients.

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Ozone therapy ameliorates tubulointerstitial inflammation by regulating TLR4 in adenine-induced CKD rats

Cited by 19 publications

References 33 publications

Salidroside Ameliorates Renal Interstitial Fibrosis by Inhibiting the TLR4/NF-κB and MAPK Signaling Pathways

Salidroside Ameliorates Renal Interstitial Fibrosis by Inhibiting the TLR4/NF-κB and MAPK Signaling Pathways

Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression

Recovery of Four COVID-19 Patients via Ozonated Autohemotherapy

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