AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats

Lu, Lijuan; Pan, Cailong; Chen, Lu; Hu, Liang; Wang, Chao-Yu; Han, Yuan; Yang, Yanjing; Cheng, Zhixiang; Li, Wentao

doi:10.1093/jmcb/mjw043

Cited by 28 publications

(18 citation statements)

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“…23,24 Our previous study demonstrated that medical ozone could attenuate neuropathic pain by activating AMPK. 25 We also demonstrated that AMPK activation could inhibit neuroinflammation via upregulate SOCS3 expression to suppress the TLR-4/p38 signaling pathway. 26 The aforementioned studies encouraged us to explore the potential protective effects of ozone therapy on chemotherapeutic enteritis and to investigate the role of AMPK/SOCS3-mediated negative inflammatory feedback in the strategy.…”

Section: Introductionmentioning

confidence: 68%

AMPK activation by ozone therapy inhibits tissue factor‐triggered intestinal ischemia and ameliorates chemotherapeutic enteritis

Yang

Zhang

et al. 2020

FASEB j.

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Chemotherapeutic enteritis is a major dose‐limiting adverse reaction to chemotherapy, with few effective drugs in clinic. Intestinal ischemic injury plays prominent role in chemotherapeutic enteritis clinically. However, mechanism is not clear. In this article, irinotecan (CPT‐11) was used to establish chemotherapeutic enteritis mice model. Western blotting, gelatin zymography, immunohistochemistry (IHC), Laser Doppler flowmetry (LDF) were used to detect the pathogenesis of ischemia‐hypoxia injury. CPT‐11 increased levels of tissue factor (TF) both in the blood and in intestines, and decreased the intestinal blood flow in mice. Interestingly, the elevation of TF in the blood displayed “double‐peak,” which was consistent with the intestinal mucosal “double‐strike” injury trend. Intestinal microthrombus and mixed thrombus formation were detectable in chemotherapeutic enteritis. Furthermore, ozone therapy relieved chemotherapeutic enteritis in mice. Ozone inhibited TF expression induced by CPT‐11 via activating AMPK/SOCS3, and effectively ameliorated the intestinal mucosal injury in mice. Moreover, ozone autotransfusion therapy effectively attenuated chemotherapeutic enteritis and the blood hypercoagulability in patients. For the first time, we proposed that TF‐induced thrombotic intestinal ischemic injury is a core trigger pathological mechanism of chemotherapeutic enteritis, and provided a new treatment strategy, ozone therapy, to suppress TF expression and treat chemotherapeutic enteritis.

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Section: Introductionmentioning

confidence: 68%

AMPK activation by ozone therapy inhibits tissue factor‐triggered intestinal ischemia and ameliorates chemotherapeutic enteritis

Yang

Zhang

et al. 2020

FASEB j.

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“…LULIN MA 1 , SONG WEN 1 , JIE YUAN 1,2 , DEXIN ZHANG 1 , YAN-LIU LU 3 , YOU ZHANG 4 , YING LI 1 and SONG CAO 1,2 oxidative and anti-pathogenic effects and immune regulation ability, as well as the increase of oxygen supply and reduction of oxidative stress (12,(20)(21)(22)(23)(24)(25)(26)(27). For instance, ozone was proven to relieve pain by causing the following effects: i) Release of endorphins (26); ii) inhibition of the activation of microglia via adenosine monophosphate (AMP)-dependent protein kinase signaling (28); iii) inhibition of the expression of purinergic receptors P2X3 and P2X7 in the spinal dorsal horn (29); iv) promoting phosphodiesterase 2A-cyclic guanosine monophosphate/cyclic AMP/NFκB-p65 signaling (30); v) inhibition of autophagy (31,32); vi) reduction of the expression of pro-inflammatory/pro-apoptotic caspases (33); and vii) increase of oxygen supply in tissues and cells (22).…”

Section: Detection Of Chlorite Chlorate and Perchlorate In Ozonated mentioning

confidence: 99%

Detection of chlorite, chlorate and perchlorate in ozonated saline

Wen

Yuan

et al. 2020

Exp Ther Med

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Medical ozone is used to treat various diseases, including numerous pathologies associated with chronic pain. Chronic pain may be treated by systemic administration of ozone, with ozonated autohemotherapy (OAH) being the commonly used method. In the clinic, intravenous infusion of ozonized saline has been used to treat various diseases. Compared with OAH, ozonized saline infusion is less technically demanding and causes minimal damage to veins. However, it has been indicated that ozone may oxidize saline and generate toxic substances, and therefore, the safety of ozone treatment has been questioned. In the present study, the potential chemical compounds produced from ozone and saline, including chlorite, chlorate and perchlorate, were examined at various time-points with ion chromatography-mass spectrometry (IC-MS). A control group (pure oxygen group) and an ozone group were included in the present study. Two subgroups were included within each group: A saline bottle (made from polypropylene) subgroup and an ozone-resistant blood transfusion bag [made from medical polyvinyl chloride, di(2-ethyl) hexyl phthalate plasticized] subgroup. For the ozone group, 100 ml saline and 100 ml medical ozone at various concentrations (20, 40 or 60 µg/ml in pure oxygen) were injected into the saline bottle or blood bag, and for the control group, 100 ml of pure oxygen was injected into the saline bottle or blood bag. The presence and the content of chlorite, chlorate and perchlorate were determined at different time-points (3, 6 and 15 days after mixing) by IC-MS. Chlorate was detected in the ozone groups at three time-points and its content increased as the ozone concentration and the reaction time increased. Under the same conditions (the same ozone concentration and the same incubation time), the chlorate content (0.90±0.14-7.69±0.48 µg/l) in the blood bag subgroup was significantly lower than that in the saline bottle subgroup (45.23±6.14-207.6±15.63 µg/l). However, chlorite and perchlorate were not detected at any time-point in the two groups. In addition, in the control group (pure oxygen group), chlorite, chlorate and perchlorate were not detected at any time-point. These results indicate that ozone reacts with saline to produce chlorate. Ozone may also react with the polypropylene saline bottle to increase the chlorate content in the bottled solution. Due to a lack of toxicology studies of chlorate in blood, it remains elusive whether ozonated saline and chlorate at the range of 0.90±0.14-7.69±0.48 µg/l has any toxic effects. The potential toxicity of chlorate should be considered when ozonated saline is used for clinical infusions.

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“…RNA isolation, reverse transcription and quantitative PCR [20] in vitro analy-5 collected, and total RNA was isolated as well. cDNA was ---Western blotting analysis 6 2 -2 at room temperature [22] Statistical analysis dent's t P<0.05 was considered Emodin decreased polarization of AAMs during acute allergic ment [11] . Therefore, we determined whether emodin attenuates in vivo in a murine asthma model.…”

Section: Murine Asthma Modelsmentioning

confidence: 99%

Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model

Song

et al. 2018

Acta Pharmacol Sin

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Alternatively activated macrophages (AAMs) are not only associated with asthma but also lead to asthmatic airway inflammation and remodeling. Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. In this study we investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone), isolated from the rhizome of Rheum palmatum, alleviated asthmatic airway inflammation and reduced AAM polarization in a murine asthma model. Mice were sensitized with a triple allergen mix containing dust mite, ragweed and aspergillus (DRA). In mice with DRA-induced asthma, asthmatic inflammation was significantly enhanced. Intraperitoneal injection of emodin (20 mg·kg·d, ip) 1 h prior to DRA challenge on days 12-14 significantly decreased pulmonary eosinophil and lymphocyte infiltration, mucus secretion and serum IgE production, as well as IL-4 and IL-5 production in bronchoalveolar lavage fluid. In response to emodin treatment, activated markers of AAM Ym-1, Fizz-1 and arginase-1 in the lung tissues were remarkably decreased. In mouse bone marrow-derived macrophages (BMDMs) in vitro, emodin (2-50 μmol/L) dose-dependently inhibited IL-4-induced AAM polarization and STAT6 phosphorylation. Collectively, our results suggest that emodin effectively ameliorates asthmatic airway inflammation and AAM polarization, and it may therefore become a potential agent for the treatment of asthma.

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AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats

Cited by 28 publications

References 50 publications

AMPK activation by ozone therapy inhibits tissue factor‐triggered intestinal ischemia and ameliorates chemotherapeutic enteritis

AMPK activation by ozone therapy inhibits tissue factor‐triggered intestinal ischemia and ameliorates chemotherapeutic enteritis

Detection of chlorite, chlorate and perchlorate in ozonated saline

Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model

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