Ozone Therapy Protects Against Rejection in a Lung Transplantation Model: A New Treatment?

Santana‐Rodríguez, Norberto; Llontop, Pedro; Clavo, Bernardino; Fiuza-Pérez, M. Dolores; Zerecero, Keila; Ayub, Adil; Alshehri, Khalid; Yordi, Nagib Atallah; Re, Lamberto; Raad, Wissam; Fernández-Pérez, Leandro; García‐Herrera, Ricardo; Huang, Chyun-Yin; Bhora, Faiz Y.

doi:10.1016/j.athoracsur.2017.02.054

Cited by 9 publications

(6 citation statements)

References 38 publications

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“…The first was a DNA microarray study of chronic rejection in lung transplantation,30 in which Hsp27 was involved in the protection of the cytoskeleton and the inhibition of apoptosis. The second study described the protective effect of ozone therapy on chronic rejection after lung transplantation, which was also associated with decreased Hsp27 expression 31. We believe that the decreased Hsp27 expression seen in the ADSC treatment groups is likely related to lesser need of expression, as less lung damage was evidenced.…”

Section: Discussionmentioning

confidence: 95%

“…The second study described the protective effect of ozone therapy on chronic rejection after lung transplantation, which was also associated with decreased Hsp27 expression. 31 We believe that the decreased Hsp27 expression seen in the ADSC treatment groups is likely related to lesser need of expression, as less lung damage was evidenced. However, further studies are required to establish the precise role of Hsp27 in PF.…”

Section: Original Researchmentioning

confidence: 90%

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Airway Transplantation of Adipose Stem Cells Protects against Bleomycin-Induced Pulmonary Fibrosis

Llontop

López-Fernández

Clavo

et al. 2018

Journal of Investigative Medicine

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Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Adipose-derived stem cells (ADSC) have demonstrated regenerative properties in several tissues. The hypothesis of this study was that airway transplantation of ADSC could protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). Fifty-eight lungs from 29 male Sprague-Dawley rats were analyzed. Animals were randomly divided into five groups: a) control (n=3); b) sham (n=6); c) BLM (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8). Animals received 500 µL saline (sham), 2.5 UI/kg BLM in 500 µL saline (BLM), and 2×10 ADSC in 100 µL saline intratracheally at 2 (BLM+ADSC-2d) and 14 days (BLM+ADSC-14d) after BLM. Animals were sacrificed at 28 days. Blinded Ashcroft score was used to determine pulmonary fibrosis extent on histology. Hsp27, Vegf, Nfkβ, IL-1, IL-6, Col4, and Tgfβ1 mRNA gene expression were determined using real-time quantitative-PCR. Ashcroft index was: control=0; sham=0.37±0.07; BLM=6.55±0.34 vs sham (P=0.006). BLM vs BLM+ADSC-2d=4.63±0.38 (P=0.005) and BLM+ADSC-14d=3.77±0.46 (P=0.005). BLM vs sham significantly increased Hsp27 (P=0.018), Nfkβ (P=0.009), Col4 (P=0.004), Tgfβ1 (P=0.006) and decreased IL-1 (P=0.006). BLM+ADSC-2d vs BLM significantly decreased Hsp27 (P=0.009) and increased Vegf (P=0.006), Nfkβ (P=0.009). BLM+ADSC-14d vs BLM significantly decreased Hsp27 (P=0.028), IL-6 (P=0.013), Col4 (P=0.002), and increased Nfkβ (P=0.040) and Tgfβ1 (P=0.002). Airway transplantation of ADSC significantly decreased the fibrosis rate in both early and established pulmonary fibrosis, modulating the expression of Hsp27, Vegfa, Nfkβ, IL-6, Col4, and Tgfβ1. From a translational perspective, this technique could become a new adjuvant treatment for patients with IPF.

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Section: Discussionmentioning

confidence: 95%

Section: Original Researchmentioning

confidence: 90%

Airway Transplantation of Adipose Stem Cells Protects against Bleomycin-Induced Pulmonary Fibrosis

Llontop

López-Fernández

Clavo

et al. 2018

Journal of Investigative Medicine

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“…In parallel to clinical advancement, an increasing number of scientific reports have been published on the biomedical effects of O 3 as adjuvant/alternative therapeutic approach for e.g., pain management [18,19,20,21,22], gastrointestinal diseases [23,24,25,26,27], lung diseases [28,29,30,31], diabetes [32,33,34,35,36,37], ischemia [38,39,40,41,42,43], cancer [44,45,46], infective diseases [47,48,49,50], dentistry [51,52,53,54,55,56].…”

Section: Ozone In the Biomedical Fieldmentioning

confidence: 99%

The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure

Galiè

Covi²,

Tabaracci³

et al. 2019

IJMS

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Ozone (O3) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O3 is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O3 exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O3 concentrations induce a moderate oxidative eustress activating antioxidant pathways. These properties make O3 a powerful medical tool, which can be used as either a disinfectant or an adjuvant agent in the therapy of numerous diseases. In this paper, the cellular mechanisms involved in the antioxidant response to O3 exposure will be reviewed with special reference to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role in the efficacy of ozone therapy.

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“…Often, the raw material for producing ozone is atmospheric air, as a more accessible source of oxygen, which leads to the appearance of additional impurities in the resulting gas mixture. [17][18][19][20] the high activity of ozone as a disinfectant is associated with its strong oxidative properties, which cause its high toxicity for macroorganisms [21,22]. Therefore, the key role in working with ozone is to determine the concentrations of ozone-containing gas mixtures that are safe for humans and animals and the conditions for their use.…”

Section: Introductionmentioning

confidence: 99%

Determination of inhalation toxicity of the ozone-air mixture

et al. 2020

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The work on the inhalation toxicity of the ozone-air mixture was carried out in two stages. At the first stage, acute inhalation toxicity was studied and the class of toxicity was determined, at the second stage, subchronic inhalation toxicity was determined. The object of the study was an ozone-air mixture. A portable standalone ozone generation device developed by us was used as a source of the mixture. A total of 58 outbred mature white Wistar rats of both sexes were used in the study, where 18 rats participated in the first stage, and 40 rats in the second. The animals were placed in an inhalation chamber. The procedure for testing acute inhalation toxicity was carried out according to the standard method at concentrations of ozone-air mixture of 100, 500, 2500 ppm and an exposure of 4 hours. As a result, the fatal outcome was observed only in 3 groups (2500 ppm), 3 out of 6 individuals were killed, including 2 males and 1 female. In fallen animals, death occurred as a result of respiratory arrest. The surviving animals were monitored for 14 days after the test. During the treatment of animals with ozone-air mixture, a gradual inhibition of the respiratory system was observed, followed by the development of pulmonary edema and respiratory failure. Based on the data obtained, the ozone-air mixture under study was assigned a hazard class 3. In the study of subchronic inhalation toxicity of oats, concentrations of 250, 125, and 50 ppm were studied. The experiment was carried out, according to the standards for determining the subchronic inhalation toxicity of substances, for 90 days. During the experiment, body weight, feed consumption, behavioral activity were recorded, and blood hematological and biochemical parameters were determined. As a result of the study of subchronic inhalation toxicity of the ozone-air mixture, no signs of intoxication were detected in rats, and there were no death cases.

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Ozone Therapy Protects Against Rejection in a Lung Transplantation Model: A New Treatment?

Cited by 9 publications

References 38 publications

Airway Transplantation of Adipose Stem Cells Protects against Bleomycin-Induced Pulmonary Fibrosis

Airway Transplantation of Adipose Stem Cells Protects against Bleomycin-Induced Pulmonary Fibrosis

The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure

Determination of inhalation toxicity of the ozone-air mixture

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