Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro.

Oxygen-ozone (O2-O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O2-O3 gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O3 stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-ß1 secretion, while in LPS-activated fibroblasts, O3 stimulated only antioxidant response and cytokines secretion. Therefore, the low O3 concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.

Photooxidation Responsive Elastin-Like Polypeptide Conjugates for Photodynamic Therapy Application.

Stimuli-responsive recombinant elastin-like polypeptides (ELPs) are artificial protein polymers derived from the hydrophobic domain of tropoelastin that have attracted significant interest for drug delivery and tissue engineering applications. In the present study, we have conjugated a photosensitizer (PS) to a hydrophobic methionine-containing ELP scaffold, which upon reaction with singlet oxygen (1O2) is transformed into a hydrophilic sulfoxide derivative facilitating the disassembly of photosensitizer-delivery particles during the photodynamic therapy (PDT) process. A peripherally substituted carboxy-Zn(II)-phthalocyanine derivative (TT1) bearing a carboxyl group directly linked to the Pc-ring, and presenting an absorption maximum around 680 nm, was selected as PS which simultaneously acted as a photooxidation catalyst. A TT1-ELP[M1V3-40] conjugate was prepared from ELP[M1V3-40] modified with an alkyne group at the N-terminal chain end, and from TT1-amide-C3-azide by copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. This innovative model photooxidation sensitive PS delivery technology offers promising attributes in terms of temperature-controlled particle formation and oxidation-triggered release, narrow molar mass distribution, reproducibility, scalability, non-immunogenicity, biocompatibility, and biodegradability for pharmaceutical applications in an effort to improve the clinical effectiveness of PDT treatments.

Combined therapies with exercise, ozone and mesenchymal stem cells improve the expression of HIF1 and SOX9 in the cartilage tissue of rats with knee osteoarthritis.

PURPOSE: Knee osteoarthritis (OA) is a common type of degenerative joint disease which decreases the quality of life. Sex-determining region Y box 9 (SOX9) and hypoxia-inducible factor-1 (HIF1) are considered as the key regulators of OA. We investigated the effect of combined therapies with mesenchymal stem cells (MSCs), ozone (O3) and exercise training on SOX9 and HIF1 expression in the cartilage of rats with knee OA. METHODS: Knee OA was induced by surgical method. OA rats were divided into model, MSCs, ozone, exercise, MSCs + ozone, MSCs + exercise, ozone + exercise and MSCs + ozone + exercise groups. Rats in the MSCs group received intraarticular injection of 1 × 106 cells/kg. Rats in the ozone group received O3 at the concentration of 20 µg/mL, once weekly for 3 weeks. Rats in the exercise group were trained on rodent treadmill three times per week. 48 hours after the programs, cartilage tissues were isolated and the expression of SOX9 and HIF1 was determined using Real-Time PCR. RESULTS: Significant differences were found in the expression of SOX9 and HIF1 between groups (P < 0.0001). Although combined therapies with exercise, MSCs and O3 significantly increased the expression of SOX9 and HIF1 in the cartilage tissue of rats with knee OA, combination of exercise with O3 was significantly more effective compared to the other combined therapies (P < 0.001). CONCLUSIONS: Combined therapy with exercise, MSCs and O3 significantly increased the expression of SOX9 and HIF1 genes in the cartilage of rats with knee OA; however, exercise + O3 was significantly more effective.

Ozone and pulsed electro-magnetic field therapies improve endometrial lining thickness in frozen embryo transfer cycles: Three case reports.

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.

Ozone therapy ameliorates inflammation and endometrial injury in rats with pelvic inflammatory disease.

As a common cause of infertility, pelvic inflammatory disease (PID) is characterized by chronic pain, ectopic pregnancy as well as inflammation and infection of the female upper genital tract. Ozone water, also known as O3, has been previously reported to be a distinctly effective agent in treating inflammation. During the present study, we asserted the hypothesis that O3 could be applied by pelvic inflammation and works to regulate the expression of inflammatory factors including interleukin-6 (IL-6), IL-2 and tumor necrosis factor-α (TNF-α). In an attempt to evaluate the effect of O3 on PID, an acute PID rat model was subsequently established. O3 at concentrations of 45 µg/mL and 60 µg/mL in addition to levofloxacin (LVLX) was injected respectively into the PID rats in a bid to alter the contents of inflammatory factors and immunologic markers. Hematoxylin-eosin (HE) staining was applied to analyze endometrial inflammation. Reductions to the contents of IL-6 and TNF-α were recorded, while that of IL-2, IgA, IgG, IgM, C3 and C4, and E rosette formation rate and transformation rate of T lymphocytes exhibited notably elevated levels after the PID rats had been injected with 45 µg/mL O3, 60 µg/mL O3 or LVLX. The pathological condition of the endometrium in rats with PID was alleviated among the PID rats after injected with the 45 µg/mL O3, 60 µg/mL O3 or LVLX. Taken together, the key findings of the current study present evidence demonstrating that the administration of O3 to the pelvic cavity ameliorated the PID conditions among rat models via inhibition of the necrosis of the endometrial epithelial cells as well as alleviated the inflammatory reactions, highlighting a potential novel PID treatment target.

Methyl jasmonate and ozone affect the antioxidant system and the quality of wine grape during postharvest partial dehydration.

Postharvest partial dehydration is a technique used in the production of important dry and sweet wines in Italy. An accurate management of the dehydration environmental parameters allows for the modulation of berry metabolism and the maintenance/improvement of the enochemical quality of grapes. As it is known that water loss induces oxidative processes in berries, our hypothesis was that methyl jasmonate (MeJA) and ozone (O3), as postharvest treatments before partial dehydration, might be beneficial for grape berry quality. Grape bunches were postharvest treated with 10 or 100 µM MeJA at 20 °C or with ozone gas at 10 °C, in 70% relative humidity (RH) and air flow, for 12 h; the control bunches were untreated and kept at 20 °C for 12 h. Subsequently, partial dehydration was performed at 10 °C until a 30% weight loss (w.l.) was reached. MeJA hastened grape berry water loss. Polyphenol and flavonoid contents at the end of the partial dehydration were lower in the MeJA-treated berries than in the control and ozone samples. Superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (GPX) activity rates increased in the treated samples. In contrast, lipoxygenase (LOX) and polyphenoloxidase (PPO) had lower activities in the MeJA-treated samples than in the controls. It would seem that MeJA accelerates grape water loss but at the same time activates the antioxidant system. Ozone does not accelerate grape water loss but induces the antioxidant system and increases polyphenol content.

The Value of Ozone in CT-Guided Drainage of Multiloculated Pyogenic Liver Abscesses: A Randomized Controlled Study.

Objective: This study was designed to compare the effects of catheter drainage alone and combined with ozone in the management of multiloculated pyogenic liver abscess (PLA). Methods: The prospective study included 60 patients diagnosed with multiloculated PLA. All patients were randomly divided into two groups: catheter drainage alone (group I) and catheter drainage combined with ozone (group II). Drainage was considered successful when (1) the abscess cavity was drained and (2) clinical symptoms were resolved. Kruskal-Wallis nonparametric test was used to compare the success rates, length of stay (LOS), and need for further surgery of the two groups. P < 0.05 indicates significant difference. Results: All patients' catheters were successfully placed under CT guidance. Group I was treated with catheters alone and group II was treated with catheters and ozone. The success rates of groups I and II were 86% and 96%, respectively (P < 0.05). And compared with group II, the duration of fever in group I was longer (P < 0.05), and the LOS was also longer (P < 0.05). Conclusion: Catheter drainage combined with ozone is an effective and safe treatment in multiloculated PLA. The Clinical Registration Number is ChiCTR1800014865.

In vitro study evaluating the instantaneous treatment of ozonised olive oil on human sperm.

OBJECTIVE: The aim of our study was to evaluate the effects of ozonised olive oil (OOO) on human sperm in vitro. METHODS: Human sperm was incubated with OOO for 20 s in vitro. The lowest concentration that completely immobilised all the sperm in 20 s without subsequent recovery of motility was recorded as the minimum effective concentration (MEC). The effects of OOO at MEC on human sperm viability, mitochondrial and acrosomal status, DNA integrity and transmission electron microscopy were observed. RESULTS: Our findings demonstrate that OOO dose-dependently inhibits sperm motility. The MEC of OOO for 100% sperm immobilisation in 20 s was 6 µg/ml. Further experiments showed that sperm ultrastructure, function and DNA integrity were significantly affected after treatment with 6 µg/ml OOO in vitro. CONCLUSIONS: OOO has spermicidal potential and may be explored as a promising vaginal contraceptive agent.

The effects of ozone on bacterial growth and thiol-disulphide homeostasis in vascular graft infection caused by MRSA in rats

Abstract: Purpose: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. Methods: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. Results: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. Conclusions: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.

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

Tubulointerstitium inflammation is a common pathway aggravating chronic kidney disease (CKD) progression and the mechanism is partly associated with excessive activation of toll-like receptor 4 (TLR4) in tubulointerstitium. Ozone therapy is demonstrated to alleviate inflammation in some experiments. The aim of this study is to examine whether ozone therapy could ameliorate chronic tubulointerstitium inflammation by suppressing TLR4 in adenine-induced CKD rats. Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and tubulointerstitium inflammation injury. Ozone therapy (1.1 mg/kg) was simultaneously administrated by rectal insufflations (i.r.). After 4 weeks, serum and kidney samples were collected for detection. Renal function and systemic electrolyte were detected. Renal pathological changes were assessed by hematoxylin-eosin (H&E) staining and Masson trichrome (MT) staining. Immunohistochemistry, Western blot and Real-time PCR were applied to evaluate tubulointerstitium inflammation as well as the expression of TLR4 and phosphorylated nuclear factor kappa B P65 (p-NF-κB P65) in rats. The results showed ozone therapy improved serious renal insufficiency, systemic electrolyte disorder and tubulointerstitium morphology damages in adenine-induced CKD rats. In addition, ozone therapy suppressed excessive activation of TLR4 and p-NF-κB P65 in the tubulointerstitium of adenine-induced CKD rats, accompanied by the reduction of inflammation-related cytokines including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). The protein expression of TLR4 was positively correlated with the protein expression levels of MCP-1 (r = 0.7863, p < 0.01) and TNF-α (r = 0.7547, p < 0.01) in CKD rats. These findings indicated ozone therapy could attenuate tubulointerstitium inflammation injury in adenine-induced CKD rats and the mechanism might associate with the mediation of TLR4.

Bombesin Receptor-Activated Protein (BRAP) Modulates NF-κB Activation in Bronchial Epithelial Cells by Enhancing HDAC Activity.

Our previous studies provided evidence that bombesin receptor-activated protein (BRAP), encoded by C6ORF89, is widely expressed in human airway epithelial cells and may play a role in the stress response of lung epithelia. In this study, we demonstrated that BRAP has a regulatory effect on NF-κB transcriptional activity in cultured human bronchial epithelial cells (HBECs). BRAP overexpression by gene transfer inhibited both basal and inducible NF-κB transcriptional activity in HBECs, whereas BRAP knockdown had the opposite effect. BRAP was shown to regulate NF-κB activity by enhancing histone deacetylase (HDAC) activity. In addition, BRAP might increase HDAC activity that leads to NF-κB activation via its putative C-terminal domain. Our study suggests that the BRAP protein is an important regulator of immune and inflammatory responses in the human airway epithelium.

Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect.

Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1ß, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone.

ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice.

Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/-) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction.

The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model.

BACKGROUND: The aim of the study was to evaulate the effect of ozone and naringin on the intestine after intestinal ischemia-reperfusion(II/R) injury. METHODS: Thirty five rats divided into 5 groups of 7 animals: control, II/R, ozone, naringin and naringin + ozone. Only laparotomy and exploration of the superior mesenteric artery (SMA) were done in control group. In the experimental groups, SAM was occluded for 1 h and reperfused for 1 h. 15 min after ischemia, ozone (25 µg/ml, 0.5 mg/kg), naringin (80 mg/kg) and naringin + ozone(80 mg/kg + 25 µg/ml, 0.5 mg/kg) were infused intraperitoneally to each groups. Ileum tissues were harvested to determine intestinal mucosal injury and oxidative stress markers. For SMA occlusion, different than literature, silk suture binding was used. RESULTS: Oxidative stress markers were significantly low in experimental groups compared with II/R group (p < 0.05). Histopathologically, the injury score was significantly low at experimental groups compared with II/R group (p < 0.05). The lowest injury score was encountered at naringine + ozone group. CONCLUSIONS: Ozone alone or combined with naringin has a protective effect for mesenteric ischemia. Instead of using instruments such as clamps in the II/R rat model, silk binding may be used safely.

Inhibitory effect of hydrogen sulfide on ozone-induced airway inflammation, oxidative stress, and bronchial hyperresponsiveness.

Exposure to ozone has been associated with airway inflammation, oxidative stress, and bronchial hyperresponsiveness. The goal of this study was to examine whether these adverse effects of ozone could be prevented or reversed by hydrogen sulfide (H2S) as a reducing agent. The H2S donor sodium (NaHS) (2 mg/kg) or vehicle (PBS) was intraperitoneally injected into mice 1 hour before and after 3-hour ozone (2.5 ppm) or air exposure, and the mice were studied 24 hours later. Preventive and therapeutic treatment with NaHS reduced the ozone-induced increases in the total cells, including neutrophils and macrophages; this treatment also reduced levels of cytokines, including TNF-α, chemokine (C-X-C motif) ligand 1, IL-6, and IL-1ß levels in bronchial alveolar lavage fluid; inhibited bronchial hyperresponsiveness; and attenuated ozone-induced increases in total malondialdehyde in bronchoalveolar lavage fluid and decreases in the ratio of reduced glutathione/oxidized glutathione in the lung. Ozone exposure led to decreases in the H2S production rate and in mRNA and protein levels of cystathionine-ß-synthetase and cystathionine-γ-lyase in the lung. These effects were prevented and reversed by NaHS treatment. Furthermore, NaHS prevented and reversed the phosphorylation of p38 mitogen-activated protein kinase and heat shock protein 27. H2S may have preventive and therapeutic value in the treatment of airway diseases that have an oxidative stress basis.

[Effect on performance ozonized perftoran cytokine profile in generalized peritonitis].

The article analyzes the results of surgical treatment of 78 patients with generalized peritonitis (GP) between the ages of 18 to 76 years. Severity was assessed by RP Mannheim peritoneal index (MPI). The study was conducted according to a comparative evaluation of the method of treatment in both groups. In the comparison group included 38 patients who received conventional therapy without immune complex. In 40 patients of the study group on the background of complex therapeutic measures in pre- and postoperative additionally used concomitant local and systemic ozone therapy (OT) with ozonatedperftoran (OP). All patients in the dynamics of blood prior to surgery, on the 3rd and 7th day after surgery was determined TNF-α, IL-4 and IL-8 by IFA. In general, patients in both groups at admission were identified imbalance between pro- and anti-inflammatory cytokines. Patients of the main group on the complex background of basic therapy combined local and systemic administration of OP positive effect in terms of acceleration available cytokine imbalance. The complex therapeutic interventions GP application of local and systemic OT with OP accelerates elimination of imbalances in the cytokine profile.

Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway, and the postnatal developing lung.

Children are uniquely susceptible to ozone because airway and lung growth continue for an extensive period after birth. Early-life exposure of the rhesus monkey to repeated ozone cycles results in region-specific disrupted airway/lung growth, but the mediators and mechanisms are poorly understood. Substance P (SP), neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling pathway components involved in ozone-induced cell death. We hypothesize that acute ozone (AO) exposure during postnatal airway development disrupts SP/NK-1R/Nur77 pathway expression and that these changes correlate with increased ozone-induced cell death. Our objectives were to 1) spatially define the normal development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how postnatal age modulates responses to AO exposure; and 3) determine how concomitant, episodic ozone exposure modifies age-specific acute responses. Male infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day × 2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day × 5 days/14-day cycle+AO). O3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle) delivered early at age 2 mo resulted in an airway that was hypersensitive to AO exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles) resulted in an airway that was hyposensitive to AO exposure at 6 mo. These observations collectively associate with greater overall inflammation and epithelial cell death, particularly in early postnatal (2 mo), distal airways.

Effect of ozone on intestinal recovery following intestinal ischemia-reperfusion injury in a rat.

BACKGROUND: Growing evidence suggests that ozone (O3) protects the host against pathological conditions mediated by reactive oxygen species by increasing the activity of antioxidant enzymes. The purpose of the present study was to examine the effect of O3 on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy; (2) sham-O3 rats underwent laparotomy and were treated with an ozone/oxygen mixture intraperitoneally and intraluminally (50 %/50 %); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 48 h of reperfusion, and (4) IR-O3 rats underwent IR and were treated with an ozone/oxygen mixture similar to group 2. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 48 h following IR. Western blot was used to determine ERK and Bax protein levels. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with p < 0.05 considered statistically significant. RESULTS: Treatment of IR rats with O3 resulted in a significant increase in mucosal weight in jejunum (70 %) and ileum (32 %), mucosal DNA (twofold increase) and protein (35 %) in ileum, villus height and crypt depth in jejunum (61 and 16 %, correspondingly) and ileum (31 and 43 %, correspondingly) compared to IR animals. IR-O3 rats also had a significantly lower intestinal injury score as well as a lower apoptotic index in jejunum and ileum compared and IR animals. A significant increase in cell proliferation rates in IR-O3 animals was accompanied by increased levels of p-ERK protein. CONCLUSIONS: Treatment with ozone prevents intestinal mucosal damage, stimulates cell proliferation and inhibits programmed cell death following intestinal IR in a rat.

Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice.

Adiponectin is an adipose-derived hormone with anti-inflammatory activity. Following subacute ozone exposure (0.3 ppm for 24-72 h), neutrophilic inflammation and IL-6 are augmented in adiponectin-deficient (Adipo(-/-)) mice. The IL-17/granulocyte colony-stimulating factor (G-CSF) axis is required for this increased neutrophilia. We hypothesized that elevated IL-6 in Adipo(-/-) mice contributes to their augmented responses to ozone via effects on IL-17A expression. Therefore, we generated mice deficient in both adiponectin and IL-6 (Adipo(-/-)/IL-6(-/-)) and exposed them to ozone or air. In ozone-exposed mice, bronchoalveolar lavage (BAL) neutrophils, IL-6, and G-CSF, and pulmonary Il17a mRNA expression were greater in Adipo(-/-) vs. wild-type mice, but reduced in Adipo(-/-)/IL-6(-/-) vs. Adipo(-/-) mice. IL-17A(+) F4/80(+) cells and IL-17A(+) γδ T cells were also reduced in Adipo(-/-)/IL-6(-/-) vs. Adipo(-/-) mice exposed to ozone. Only BAL neutrophils were reduced in IL-6(-/-) vs. wild-type mice. In wild-type mice, IL-6 was expressed in Gr-1(+)F4/80(-)CD11c(-) cells, whereas in Adipo(-/-) mice F4/80(+)CD11c(+) cells also expressed IL-6, suggesting that IL-6 is regulated by adiponectin in these alveolar macrophages. Transcriptomic analysis identified serum amyloid A3 (Saa3), which promotes IL-17A expression, as the gene most differentially augmented by ozone in Adipo(-/-) vs. wild-type mice. After ozone, Saa3 mRNA expression was markedly greater in Adipo(-/-) vs. wild-type mice but reduced in Adipo(-/-)/IL-6(-/-) vs. Adipo(-/-) mice. In conclusion, our data support a pivotal role of IL-6 in the hyperinflammatory condition observed in Adipo(-/-) mice after ozone exposure and suggest that this role of IL-6 involves its ability to induce Saa3, IL-17A, and G-CSF.

Selective DNA purine base photooxidation by bis-terdentate iridium(III) polypyridyl and cyclometalated complexes.

Two bis-terdentate iridium(III) complexes with polypyridyl and cyclometalated ligands have been prepared and characterized. Their spectroscopic and electrochemical properties have been studied, and a photophysical scheme addressing their properties is proposed. Different types of excited states have been considered to account for the deactivation processes in each complex. Interestingly, in the presence of mono- or polynucleotides, a photoinduced electron-transfer process from a DNA purine base (i.e., guanine or adenine) to the excited complex is shown through luminescence quenching experiments. For the first time, this work reports evidence for selective DNA purine bases oxidation by excited iridium(III) bis-terdentate complexes.