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Effect of ischemia reperfusion and ozone pretreatment to ischemia reperfusion in jejunum and ileum (stained with hematoxylin-eosin, magnification ×200). Desquamation of the epithelium and denuded villi (asteriks) in both jejenum (a) and ileum (b) of IR group. Shortened and thick villi in both jejenum (c) and ileum (d) of ozone pretreated IR group. A less marked subepithelial space (arrow) at the villus tip in ileum.
Source publication
Objectives:
Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine.
Material and method:
Twenty eight Wistar rats were randomized into fo...
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Citations
... The increased ozone dosage, which was thought to be more beneficial, was determined based on current literature. [7] All rats were fasted and killed 24 h following de-occlusion. Two centimeter specimens of the small intestine were resected (5 cm away from the terminal ileum) for histopathological and biochemical examinations. ...
... While Dere Günal et al. could not see an increase in the antioxidant system by giving 0.7 mg/ kg ozone in ischemia/reperfusion injury, Onal et al. applied preconditioning before ischemia/reperfusion by giving ozone at a dose of 1 mg/kg for 5 days as we did and they saw its benefit. [7] Another significant difference between our study and Dere Günal et al. is that they evaluate the SOD instead of GSH activity to evaluate the antioxidant system. SOD and GSH are essential markers to evaluate the antioxidant system. ...
Background:
Ischemia/reperfusion injury of the intestines is a severe surgical condition. This study aimed to reveal ozone therapy effects with relatively increased ozone dosage in a created ischemia/reperfusion injury model.
Methods:
In this study, 24 albino Wistar rats were examined in three groups. Rats in the control group (CG, n=8) underwent only a laparotomy. In the sham group (SG, n=8) and ozone group (OG, n=8), the superior mesenteric artery (SMA) of the rats was occluded for 1 h. After deoccluding the SMA, the abdomen was closed, physiological saline was infused intraperitoneally in the SG, and an increased ozone/oxygen mixture dose (from 0.7 mg/kg to 1 mg/kg) was infused intraperitoneally in the OG. Small intestine samples were obtained at the 24th h for histopathological examination of intestinal mucosal injury and evaluated according to the Chiu score. In addition, Malondialdehyde and Myeloperoxidase levels were evaluated for oxidant levels, whereas, Glutathione (GSH) enzyme activity was measured to evaluate the tissue antioxidant system.
Results:
Histopathologically, the Chiu score was the lowest in the CG. It was lower in the OG compared to the SG showing the ameliorating effect of ozone on the intestinal mucosa. Chiu score in the OG was higher compared to that in the CG, but not statistically significant. A significantly higher GSH level was observed in the OG compared to the SG, proving antioxidant activity.
Conclusion:
In this experimental model of ischemia/reperfusion in rats, treatment with an increased ozone level decreased the inflammatory process through antioxidant mechanisms and reduced intestinal mucosal damage. However, the effectiveness of ozone therapy depends on its dosages.
... Furthermore, ozone has demonstrated effective antibacterial activity in rats with induced peritonitis [11]. Ozone intraperitoneal administration in rats reduced the lesions of the intestinal mucosa caused by the phenomenon of ischemia-reperfusion associated with the increase of antioxidant enzymes [12]. Blood circulation and oxygenation of ischemia tissues have also been improved as a result of ozone therapy [13]. ...
Simple Summary: Wounds of the extremities in cats accompanied by considerable loss of substance are frequently encountered in current practice and their therapeutic management and choice of closing method is a challenge for the veterinarian while also exerting an influence on the evolution of healing. In this case report, a new complementary technique is proposed, which involved supporting a skin graft using ozone therapy both before and after applying the graft. This approach accelerated the recovery of the patient and no complications were observed. Abstract: This case report describes a new therapeutic approach for a domestic shorthaired female cat, who has an extensive posttraumatic wound in the right hind limb. After patient stabilization, general anesthesia was started and the wound was cleaned and debrided of devitalized tissues, followed by the application of ozone therapy and bandage. Eight sessions of ozone therapy were performed for 17 days until the application of the skin graft. Three more sessions of ozone therapy were performed every 3 days postoperatively. The bagging method and the perilesional infiltration method were used. The ozone therapy ensured an accelerated recovery of the patient without any complications. According to our knowledge, this is the first case report with the use of ozone therapy to support a free skin graft in a cat. The new therapeutic approach could be used to accelerate healing of the wounds with a significant lack of substance, by supporting pre-and post-operative skin grafts.
... An increase in SOD levels after ozone treatment has been described previously [21,38,39]. We attempted to develop a protocol for measuring SOD levels in a cell culture medium using the SOD Colorimetric Activity Kit (Thermo Fisher Scientific) to simulate serological levels of the enzyme. ...
... In contrast with some prior studies [21,38], we observed a progressive decrease in CAT levels as we increased the ozone concentration. CAT levels are an indicator of mitochondrial oxidative stress. ...
... Few studies have evaluated the effect of ozone as a treatment for in vitro ischemia. Most studies used ozone for preconditioning cells, which were subjected to hypoxia only after treatment with the gas [38,39,[47][48][49][50][51][52]. Similar to our study, Cai et al. [21] used ozone after inducing hypoxia. ...
Encephalic vascular accident, or stroke, is the most common pathology of the central nervous system in humans, the second leading cause of death and physical and cognitive disabilities, in developing countries. It presents as an ischemic (more common) or hemorrhagic form. Ozone therapy has been shown to be effective in neuromodulation, neuroprotection, and nerve regeneration. The present study aimed to evaluate the effect of targeted mild ozone after inducing cerebral ischemia in vitro. Neuroblastoma lineage cells (SH-SY5Y) and canine amniotic membrane stem cells were subjected to 24 hours of hypoxia in an incubator culture chamber. The cells were evaluated by MTT assay, colorimetric assay spectrophotometry, fluorescence microscopy, and flow cytometry. Treatment with low concentrations of ozone (2–10 µg/mL), indicated a possible neuroregenerative effect at low concentrations, correlated with lower levels of apoptosis and oxidative stress compared to cells not subjected to hypoxia. High concentrations of ozone (18–30 µg/mL) promoted an increase in rate of apoptosis and cell death. We developed a novel protocol that mimics ozone therapy for ischemic stroke, using ozonized culture medium after hypoxia induction. Although more studies are needed, we conclude that ozone has a dose-dependent hormetic effect and can reverse the effect of ischemia in vitro at low concentrations.
... In recent years, ozone therapy has been widely applied to the treatment of multiple human diseases as a complementary medical approach [8]. It has been reported that preconditioning with small doses of ozone protects kidney, intestinal mucosa and brain from ischemia-reperfusion injury in animal models [13][14][15]. Wu et al. [9] demonstrated that therapeutic dosage of ozone can attenuate chemically induced damage of nerve roots in radiculoneuritis rat. In rat model of experimental uveitis, ozone therapy decreases inflammation in histopathologic examination when compared with the sham group [16]. ...
Background
Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR).
Material and methods
After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin–eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting.
Results
Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment.
Conclusions
Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.
... In the group pre-treated with O3, using 3 L/min of an O2 (97%)-O3 (3%) gas mixture with 60 μg/mL O3, volume 3.2-4.2 ml, the animals exhibited a decreased intestine mucosa injury and increased total antioxidant capacity (TAC), SOD, glutathione peroxidase and catalase [206]. ...
... An increase in NO following O3 treatment was reported very recently also by Yasemin Dere Günal and colleagues in an ischemia/reperfusion (I/R) injury model in male Wistar rats [212]. However, in these I/R injury models with rats, protocols are crucial to envisage a positive result from using O3 as a profilactic Table 1) [206]. The correct O3 protocol is mandatory to earn positive outcome in the use of this gas. ...
... Endothelial dysfunction plays a major role in I/R injury [219]. Wistar rats, undergoing superior mesenteric artery occlusion for 1 hour and reperfusion for two hours, when administered with 1.0 mg/kg of O3 increased intestinal tissue levels of SOD, glutathione peroxidase and catalase [206]. Moreover, tissue protection from I/R injury by O3 may involve the activation of iNOS. ...
An increasing amount of reports in the literature is showing that medical ozone (O3) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O3 to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O3 should act on COVID-19. The knowledge on how O3 works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.
... In rats, the effects of ozone therapy on oxidative stress markers remain controversial. While one study demonstrated that intraperitoneal ozone applied for five days was sufficient to increase TAC (Onal et al., 2015), another study showed that two different doses of intraperitoneal ozone applied for ten days resulted in a decrease of TAC (Simos et al., 2011). One of the limitations of the present study is that the uterine ozone therapy protocol was performed for only 3 days, a period shorter than that used in rats, which may have contributed to the divergence of results. ...
... While the TOC increased after ozone therapy, there was no increase in lipid peroxidation using TBARS. Tsuzuki et al. (2016) observed no increase in oxidizing compounds after ozone therapy by major autohemotherapy in horses and Onal et al. (2015) detected a decrease of TOC in rats following intraperitoneal ozone therapy. Such discrepancies may be due to the methodologies used to determine TOC and to species-specific responses to oxidative aggressions. ...
... In humans, the increase in TBARS after ozone therapy has been demonstrated in one patient with myocardial infarction (Hernández, 2007) and after blood ozonation . In rats, similar to our results, no increase was seen in TBARS at 5 (Onal et al., 2015) or 15 (Kesik et al., 2009) days following intraperitoneal ozone therapy. In this study, lipid peroxidation was likely restricted to the uterus, or the oxidative stress triggered was not enough to increase lipid peroxidation to systemic levels. ...
With the purpose of assessing the effects of uterine ozone therapy and anticoagulant sampling on oxidative stress (OS) parameters in mares, ten mares underwent three consecutive days of uterine ozone therapy by flushing the uterus with ozonated lactated Ringer's solution followed by insufflation with ozone‑oxygen gas. Serum samples were obtained at baseline and days 3, 6, 10 and 17 to determine the effect of ozone therapy on OS markers. Plasma obtained with anticoagulants citrate, ethylenediaminetetraacetic acid (EDTA) and heparin were at baseline and 6 days following therapy to determine the effect of anticoagulant on OS parameters. Antioxidants albumin and uric acid, total antioxidant capacity (TAC) using four different methods, total oxidant capacity (TOC) and lipid peroxidation were determined through photocolorimetry. Statistical analyses comprised repeated measures ANOVA followed by Dunnett's test or Friedman followed by Dunn's post-hoc test. Differences were considered significant when p < 0.05. Uterine ozone therapy significantly decreased uric acid, TAC in all four different methods, concomitantly with an increase on TOC at days 3 and 6 following therapy. No changes were observed on albumin and lipid peroxidation levels. Anticoagulants prevented the detection of oxidative stress induced by uterine ozone therapy depending on the method of analysis. In conclusion, uterine ozone therapy causes systemic oxidative stress in mares and the choice of anticoagulant sampling interferes with laboratory tests.
... Various experimental studies assessed the antioxidative effects of ozone therapy (Table 1), mostly in rats with ischemia-reperfusion injury (IRI) because oxidative stress largely contributes to IRI [91,92]. Hepatic [93,94], renal [95,96], intestinal [97], cochlear [98], retinal [99] and testicular [100] tissues among others have been investigated so far. According to these studies, ozone therapy has a protective role against IRI by shifting the redox balance towards the antioxidant activity. ...
Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS
... In the present study, data analysis from the IR group indicated a significant decrease in intestinal TAC and increase in MDA and NO. These results are in consistent with previous studies which indicated that intestinal oxidative stress was increased with IR [30][31][32]. ...
Objective
Intestinal ischemia reperfusion (IR) is a pathophysiologic process that leads to oxidative stress and acute inflammatory responses. Understanding the mechanisms explaining this inflammation is essential to developing therapeutic strategies. Therefore, the purpose of this study was to evaluate the protective outcome of modafinil (Mod) against intestinal damages caused by intestinal IR injury.
Methods/materials
Fourty adult Male Wistar rats were randomly divided into four groups: sham control group; intestinal IR group; Mod pre-treated IR group and Mod post-treated IR group. Mod in a dose of 10 mg/kg was injected intraperitoneally once daily for 7 days pre or post IR treatment.
Results
Mod significantly attenuated the IR induced elevations in intestinal malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin 1-β (IL-1β) and P-glycoprotein (P-gp) levels, caspase-3 activity. However, a significant increase in TAC was reported as compared with the IR group but its post-treated IR group was highly protective. Mod post-treatment down-regulated the IR induced cyclo-oxygenase-2 (COX-2) over-expression. Distorted mucosa with loss of surface epithelial cells, epithelial separation oedematous lamina propria and inflammatory cellular infiltration detected by histopathological examination of intestinal tissue, were markedly ameliorated by Mod post-treatment.
On the other hand, Mod pre-treatment showed less protection against intestinal IR in rats.
Conclusion
Current study suggests that Mod post-treatment ameliorated intestinal damages, so it can be considered a potential therapeutic agent to protect against the major clinical challenge of intestinal injury resulting from IR.
... no effective therapeutic regimen has yet been described in the medical literature. [2,4,[6][7][8] Ozone (O3) is a colorless gas having a characteristic odor at room temperature, consisting of three oxygen atoms. Ozone has adverse effects on the human body, such as damage to cells and tissues, because of its strong oxidation activity, especially at high concentrations. ...
... Furthermore, it may also affect the production and release of proinflammatory cytokines from inflammatory cells and activate the immune and neuroendocrine systems by increasing the blood circulation and oxygen delivery at low doses. [2,[6][7][8][12][13][14][15] Due to these antioxidant and anti-ischemic effects, clinical studies have suggested that ozone therapy is useful to treat many diseases, including peritonitis, wound infections, burns, skin ulcers, and gangrene. [6,7] However, there are few experimental studies regarding the effects of ozone on intestinal I/R injury and also there is a lack of standardization among them. ...
... [2,[6][7][8][12][13][14][15] Due to these antioxidant and anti-ischemic effects, clinical studies have suggested that ozone therapy is useful to treat many diseases, including peritonitis, wound infections, burns, skin ulcers, and gangrene. [6,7] However, there are few experimental studies regarding the effects of ozone on intestinal I/R injury and also there is a lack of standardization among them. ...
Background:
In this study, we aimed to examine the therapeutic effects of ozone on the acute phase of intestinal ischemia-reperfusion (I/R) injury in rats to resemble clinical practice.
Methods:
Eighteen Wistar albino rats were assigned to control (CG, n=6), sham (SG, n=6) and ozone groups (OG, n=6). A midline laparotomy was performed and a superior mesenteric artery (SMA) in the SG and OG was occluded with a 0/0 catgut suture, but in the CG, the incision was closed without any intervention. Tissue oxygenation was monitored with a tissue oxygenation monitor to achieve the same grade during intestinal ischemia. The incision was closed and, in the OG, ozone/oxygen mixture (0.7 mg/kg) was injected intraperitoneally, 20 minutes before reperfusion. Surgical incision was reopened and reperfusion was achieved after 60 minutes of ischemia in the SG and OG. After 60 minutes of reperfusion, 2 cm small intestine segment was sampled for histopathological assessment of the intestinal mucosal damage (Chiu score) and biochemical assessment of oxidative stress markers (nitric oxide: NO, malondialdehyde: MDA, superoxide dismutase: SOD) in all groups.
Results:
The Chiu scores of the SG and OG were statistically increased than that of the CG (p=0.002; and p=0.002, respectively). Chiu score in the OG was higher compared to that in the SG, but not statistically significant (p=0.175). MDA levels were statistically higher in the SG and OG than that of the CG (p=0.004; and p=0.010, respectively). However, the difference between the SG and OG was not statistically significant (p=0.522). SOD and NO levels were not significantly different between groups (p=0.451 and p=0.056, respectively).
Conclusion:
Contrary to the literature, single-dose ozone therapy did not reduce the oxidative stress or improve the ischemic damage in intestinal I/R injury in rats. Further evaluation with different doses in different time periods is needed for potential clinical use.
... Recently, intrarectal application of MO has been shown to reduce ROS by stimulating and/or preserving endogenous antioxidant systems in experimental reperfusion models of hepatic and renal ischemia. [28] Preconditioning with MO reduced the pulmonary wet/dry ratio, neutrophil infiltration, lipid membrane peroxidation and increased SOD activity in the lungs after intestinal I/R. Consistent with these observations, histopathological analysis also indicated that preconditioning could improve lung injury induced by intestinal I/R injury. ...
COVID-19 is the disease caused by the new coronavirus SARS-CoV-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms, to severe respiratory failure and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high risk of mortality.COVID 19 is characterized by an abnormal inflammatory response similar to a cytokine storm, which is associated with endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its potentially life-threatening complications.Numerous experimental and clinical observations have suggested that the gut microbiota plays a key role in sepsis and ARDS pathogenesis. The incidence of diarrhea in COVID-19 patients and the high mortality rate in elderly patients, considered together, indicate a possible involvement of the intestine-lung axis in COVID-19 with association of dysbiosis.Ozonetherapy is the administration of a mixture of ozone and oxygen, or Medical Ozone (MO), which produces a series of benefits capable of counteracting a wide range of pathologies, in use for over a century as an unconventional medicine practice.MO is fundamental to inhibit the activation of the inflammatory reaction and to obtain an antioxidant activity both in the tissue and in the blood. Oxidative ozone preconditioning causes an increase in SOD, GSH-Px values.MO, using large auto-hemo-infusion or rectal insufflation technique or ozonized water, could help oxygenate the tissues better, decrease gut inflammation and regulate immune response, help slow down viral growth, regulate circulation and avoid or slow down vascular hypertrophy and consequent hyperemia , especially in the early stages, with obvious benefit at microbiome level.
