scholarly journals Effect of parenteral selenium administration on oxidative status of weaned piglets

2016 ◽  
Vol 85 (4) ◽  
pp. 377-386
Author(s):  
Martin Svoboda ◽  
Zdeněk Fajt ◽  
Jan Vašek ◽  
Jonáš Vaňhara ◽  
Martin Hostovský ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sodium Selenite ◽  
Feed Consumption ◽  
Serum Concentrations ◽  
Weaned Piglets ◽  
Negative Effects ◽  
Group 3 ◽  
Group 2 ◽  
Positive Effect ◽  
Group 1

The aim of the study was to evaluate the effect of additional selenium injection after weaning on the selenium (Se) status of piglets and to find whether the selected dose would be appropriate with respect to the level of oxidative stress. Another goal was to compare the efficacy and safety of sodium selenite and selenopyran as selenium sources for parenteral administration to piglets. Altogether 30 piglets were divided equally into three groups. Piglets in group 1 were injected i.m. with sodium selenite, piglets in group 2 were injected with selenopyran. The dose was 0.42 mg Se/kg body weight for both groups. Piglets in group 3 were given only saline. As expected, the study revealed low Se serum concentrations in weaned piglets. The injection of sodium selenite increased Se serum concentrations but did not have a positive effect on the peroxidase activities. Administration of selenopyran did not influence Se concentrations and gluthation peroxidase activities. The selected dose did not have a significant impact on the level of the oxidative stress. The piglets receiving Se only from the feed achieved comparable gluthation peroxidase activities during the trial. It seems that despite initially low Se concentrations, the physiological requirements for gluthation peroxidase synthesis were met with the feed consumption as the only Se source. The results of the study are important because until now it was unclear whether the selected dose would have negative effects on the organism with respect to the induction of oxidative stress in piglets.

Cholinesterase Activities and Oxidative Stress in Cattle Experimentally Exposed to Nitrate/Nitrite in Cultivated Pasture with Different Fertilization Schemes

2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Cholinesterase Activity ◽  
Blood Samples ◽  
Group 3 ◽  
Cholinesterase Activities ◽  
Group 2 ◽  
Nitrate And Nitrite ◽  
And Oxidative Stress ◽  
Group 1

  Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or en­vironmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes. Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three dif­ferent paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective pad­dock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following param­eters: levels of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups. Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.Keywords: plant toxicology, poisoning, methemoglobin, cholinergic system, oxidative stress.

scholarly journals Melatonin attenuates ovarian ischemia reperfusion injury in rats by decreasing oxidative stress index and peroxynitrite

2020 ◽  
Vol 50 (6) ◽  
pp. 1513-1522
Author(s):  
Şenol KALYONCU ◽  
Bülent YILMAZ ◽  
Mustafa DEMİR ◽  
Meltem TUNCER ◽  
Zehra BOZDAĞ ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stress Index ◽  
Oxidative Stress Index ◽  
Group 6 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background/aim: To evaluate the protective effect of melatonin on ovarian ischemia reperfusion injury in a rat model. Materials and methods: Forty-eight rats were separated equally into 6 groups. Group 1: sham; Group 2: surgical control with 3-h bilateral ovarian torsion and detorsion; Group 3: intraperitoneal 5% ethanol (1 mL) just after detorsion (as melatonin was dissolved in ethanol); Group 4: 10 mg/kg intraperitoneal melatonin 30 min before 3-h torsion; Group 5:10 mg/kg intraperitoneal melatonin just after detorsion; Group 6:10 mg/kg intraperitoneal melatonin 30 min before torsion and just after detorsion. Both ovaries and blood samples were obtained 7 days after detorsion for histopathological and biochemical analysis.Results: In Group 1, serum levels of total oxidant status (TOS) (μmol H2O2 equivalent/g wet tissue)were significantly lower than in Group2 (P = 0.0023), while tissue TOS levels were lower than in Group 3 (P = 0.0030). Similarly, serum and tissue levels of peroxynitrite in Group 6were significantly lower than those ofGroup 2 (P = 0.0023 and P = 0.040, respectively). Moreover, serum oxidative stress index (OSI) (arbitrary unit) levels were significantly increased in Group 2 when compared to groups 1 and 6 (P = 0.0023 and P= 0.0016, respectively) and in Group 3 with respect to groups 1, 4, 5, and 6 (P = 0.0023, P = 0.0026, P = 0.0008, and P = 0.0011, respectively). Furthermore, there was a significant decrease in histopathological scores including follicular degeneration, vascular congestion, hemorrhage, and inflammation in the melatonin and sham groups in comparison with control groups. Additionally, primordial follicle count was significantly higher in Group 6 than in Group 2 (P = 0.0002).Conclusion: Melatonin attenuates ischemia reperfusion damage in a rat torsion/detorsion model by improving histopathological and biochemical findings including OSI and peroxynitrite.

scholarly journals Pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, for COVID-19-related moderate pneumonia: a randomized, double-blind, placebo-controlled, phase IIa study

2021 ◽  
Author(s):  
Benjamin Gaborit ◽  
Eric Dailly ◽  
Bernard Vanhove ◽  
Régis Josien ◽  
Karine Lacombe ◽  
...  
Keyword(s):  
Adverse Events ◽  
High Serum ◽  
Serum Concentrations ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Good Tolerability ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Objective: We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. To evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. Methods : In this phase 2a trial, adults with COVID-19-related moderate pneumonia of ≤10 days duration were randomized to infusion of XAV-19 0.5mg/kg at day 1 and day 5 (group 1), 2mg/kg at day 1 and day 5 (group 2), 2mg/kg at day 1 (group 3) or placebo. Results : Eighteen patients (n=7 for group 1, n=1 for group 2, n=5 for group 3, and n=5 for placebo) were enrolled. Baseline characteristics were similar across groups, XAV-19 serum concentrations (μg/mL, median, range) at C max and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 μg/mL (tow fold the in vitro 100% inhibitory concentration [IC 100 ]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug. Conclusions : Single intravenous dose of 2mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. Trial registration: ClinicalTrials.gov Identifier: NCT04453384

scholarly journals Xenogeneic and Allogeneic Mesenchymal Stem Cells Effectively Protect the Lung Against Ischemia-reperfusion Injury Through Downregulating the Inflammatory, Oxidative Stress, and Autophagic Signaling Pathways in Rat

2020 ◽  
Vol 29 ◽  
pp. 096368972095414
Author(s):  
Kun-Chen Lin ◽  
Jun-Ning Yeh ◽  
Yi-Ling Chen ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Damage Cell ◽  
Group 4 ◽  
Flow Cytometric ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

This study tested the hypothesis that both allogenic adipose-derived mesenchymal stem cells (ADMSCs) and human inducible pluripotent stem cell-derived MSCs (iPS-MSCs) offered a comparable effect for protecting the lung against ischemia-reperfusion (IR) injury in rodent through downregulating the inflammatory, oxidative stress, and autophagic signaling pathways. Adult male Sprague–Dawley rats ( n = 32) were categorized into group 1 (sham-operated control), group 2 (IRI), group 3 [IRI + ADMSCs (1.0 × 106 cells)/tail-vein administration at 0.5/18/36 h after IR], and group 4 [IRI + iPS-MSCs (1.0 × 106 cells)/tail-vein administration at 0.5/18/36 h after IR], and lungs were harvested at 72 h after IR procedure. In vitro study demonstrated that protein expressions of three signaling pathways in inflammation (TLR4/MyD88/TAK1/IKK/I-κB/NF-κB/Cox-2/TNF-α/IL-1ß), mitochondrial damage/cell apoptosis (cytochrome C/cyclophilin D/DRP1/ASK1/APAF-1/mitochondrial-Bax/caspase3/8/9), and autophagy/cell death (ULK1/beclin-1/Atg5,7,12, ratio of LCB3-II/LC3B-I, p-AKT/m-TOR) were significantly higher in lung epithelial cells + 6h hypoxia as compared with the control, and those were significantly reversed by iPS-MSC treatment (all P < 0.001). Flow cytometric analysis revealed that percentages of the inflammatory cells in bronchioalveolar lavage fluid and circulation, and immune cells in circulation/spleen as well as circulatory early and late apoptotic cells were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4 (all P < 0.0001). Microscopy showed the lung injury score and numbers of inflammatory cells and Western blot analysis showed the signaling pathways of inflammation, mitochondrial damage/cell apoptosis, autophagy, and oxidative stress exhibited an identical pattern of flow cytometric results among the four groups (all P < 0.0001). Both xenogeneic and allogenic MSCs protected the lung against IRI via suppressing the inflammatory, oxidative stress, and autophagic signaling.

scholarly journals Microbiological analysis in the fixation and preservation of dog cadavers with ethyl alcohol and sodium chloride solution

2019 ◽  
Vol 40 (6Supl2) ◽  
pp. 3099
Author(s):  
Natália Pereira ◽  
Marita Vedovelli Cardozo ◽  
Thiago André Salvitti de Sá Rocha ◽  
Raphael Chiarelo Zero ◽  
Fernando Antônio de Ávila ◽  
...  
Keyword(s):  
Sodium Chloride ◽  
Ethyl Alcohol ◽  
Chloride Solution ◽  
Sodium Chloride Solution ◽  
Microbiological Analysis ◽  
Negative Effects ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

There are several fixative or preservative solutions for use on cadavers, and formaldehyde is the most widely used. However, this chemical may present negative effects for professionals who manipulate it. Therefore, this study aimed to identify and quantify the main microorganisms related to the fixation and preservation of dog cadavers using an alternative and formaldehyde-free solution. After arterial injection (120 mL kg?1 95% 96° GL ethyl alcohol and 5% pure glycerin), cadavers were placed in 96° GL ethyl alcohol for 30 (group 1), 60 (group 2), 90 (group 3), and 120 days (group 4). After the fixation period, they remained under preservation in a 30% aqueous sodium chloride solution for 120 days. Bacterial quantification was performed by the pour plate method. The bacterial population was present in all groups during fixation, except for group 1, but never exceeded 9 × 101 CFU mL?1 in total aerobes and 7 × 101 CFU mL?1 in total anaerobes. The microbial population was present in all groups in at least two moments during preservation and never exceeded 7 × 101 CFU mL?1 in total aerobes and anaerobes. The presence of fungi was observed in 8 out of 34 analyses. Pseudomonas sp., Escherichia coli, and Bacillus sp. were identified in the analyzed samples. Microbiological counting was low, and no signs of contamination were observed in the vats at visual inspection.

scholarly journals Effects of water quality and stocking density on growth performance of juvenile cod (Gadus morhua L.)

2006 ◽  
Vol 63 (2) ◽  
pp. 326-334 ◽  
Author(s):  
Björn Björnsson ◽  
Sólveig R. Ólafsdóttir
Keyword(s):  
Growth Rate ◽  
Gadus Morhua ◽  
Stocking Density ◽  
Ammonia Nitrogen ◽  
Limiting Factor ◽  
Negative Effects ◽  
Total Ammonia ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract In a 5-month experiment where groups of juvenile cod were reared in a flow-through system at low density (Group 1) and in a recirculating system at low (Group 2) and high densities (Group 3), the recirculated water had negative effects on growth rate, nutritional condition, and mortality. After the first month, mean weight was significantly larger in Group 1 than in the other two groups. The effect of stocking density on mean weight was not significant until the end of the experiment, when densities were 9.0 and 48.3 kg m−3 in Groups 2 and 3, respectively. Initial mean weight of fish was 37.3 g and at the termination of the experiment mean weights were 225.2, 181.8, and 167.9 g in Groups 1, 2, and 3, respectively. After 5 months, mean condition factors were 1.074, 0.965, and 0.946, mean liver indices 9.5, 9.0, and 7.6, and mean mortalities over the course of the experiment were 1.0%, 5.1%, and 2.4% in Groups 1, 2, and 3, respectively. Water temperature (10.4–10.6°C), pH (7.2–7.4) and oxygen concentration (8–10 mg l−1) were similar among groups. Concentration of total ammonia nitrogen (TAN) was similar among groups for the first half of the experiment (0.3–0.4), but during the last month it was 0.6, 1.3, and 1.5 mg l−1 in Groups 1, 2, and 3, respectively. There was a negative correlation (r2 = 0.48, n = 36) between relative growth rate and TAN, suggesting that ammonia may have been a limiting factor in the recirculating system. The apparent threshold limit of TAN for reduced growth was approximately 1 mg l−1.

Acute vs. chronic effects of elevated hemoglobin O2 affinity on O2 transport in maximal exercise

2000 ◽  
Vol 89 (1) ◽  
pp. 265-272 ◽  
Author(s):  
Kyle K. Henderson ◽  
Web McCanse ◽  
Tetsuya Urano ◽  
Ichiro Kuwahira ◽  
Richard Clancy ◽  
...  
Keyword(s):  
Maximal Exercise ◽  
Saturation Pressure ◽  
Relative Magnitude ◽  
Extraction Ratio ◽  
Negative Effects ◽  
Arterial Blood ◽  
Group 3 ◽  
Group 2 ◽  
Sodium Cyanate ◽  
Group 1

These studies were conducted to compare the effects on systemic O2 transport of chronically vs. acutely increased Hb O2 affinity. O2 transport during maximal normoxic and hypoxic [inspired Po 2(Pi O2 ) = 70 and 55 Torr, respectively] exercise was studied in rats with Hb O2 affinity that was increased chronically by sodium cyanate ( group 1) or acutely by transfusion with blood obtained from cyanate-treated rats ( group 2). Group 3 consisted of normal rats. Hb O2 half-saturation pressure (P50; Torr) during maximal exercise was ∼26 in groups 1 and 2 and ∼46 in group 3. In normoxia, maximal blood O2 convection (T˙o 2 max = cardiac output × arterial blood O2 content) was similar in all groups, whereas in hypoxia T˙o 2 max was significantly higher in groups 1 and 2 than in group 3. Tissue O2 extraction (arteriovenous O2 content/arterial O2 content) was lowest in group 1, intermediate in group 2, and highest in group 3 ( P < 0.05) at all exercise Pi O2 values. In normoxia, maximal O2 utilization (V˙o 2 max) paralleled O2extraction ratio and was lowest in group 1, intermediate in group 2, and highest in group 3( P < 0.05). In hypoxia, the lower O2extraction ratio values of groups 1 and 2 were offset by their higher T˙o 2 max; accordingly, their differences inV˙o 2 max from group 3 were attenuated or reversed. Tissue O2 transfer capacity (V˙o 2 max/mixed venous Po 2) was lowest in group 1 and comparable in groups 2 and 3. We conclude that lowering Hb P50 has opposing effects onT˙o 2 max and O2 extraction ratio, with the relative magnitude of these changes, which varies with Pi O2 , determiningV˙o 2 max. Although the lower O2 extraction ratio of groups 2 vs. 3suggests a decrease in tissue Po 2 diffusion gradient secondary to the low P50, the lower O2extraction ratio of groups 1 vs. 2 suggests additional negative effects of sodium cyanate and/or chronically low Hb P50 on tissue O2 transfer.

scholarly journals Influence of biopreparations on the postnatal period of highly productive cows

2021 ◽  
Vol 935 (1) ◽  
pp. 012041
Author(s):  
V G Semenov ◽  
E P Simurzina ◽  
S G Kondruchina ◽  
V G Tyurin ◽  
A F Kuznetsov ◽  
...  
Keyword(s):  
Effective Means ◽  
Blood Parameters ◽  
Postnatal Period ◽  
Control Group ◽  
Milk Productivity ◽  
Service Period ◽  
Group 3 ◽  
Group 2 ◽  
Positive Effect ◽  
Group 1

Abstract The article describes the results of comparative studies on the influence of new immunostimulants on the course of postnatal recovery of the cows under conditions of intensive milk production technology. Injections of PS-2 (group 1) and Prevention-N-E (group 2) at a dose of 10 ml forty, twenty and ten days before calving, and a injection of PDE at a dose of 20 ml with E-Selenium of 10 ml (group 3) twenty days before calving prevent the occurrence of obstetric and gynecological pathology, improve reproductive qualities, as compared to the control group, where no biologicals were injected. This fact impacts the acceleration of the first heat onset by 13.7-21.1 days, the conception rate by 0.5-0.7 times, the service period by 16-29.9 days. A positive effect of the tested agents on metabolic processes, morphological and biochemical blood parameters, nonspecific immunological reactivity of the organism was also established. All these factors led to an increase in milk productivity for 305 days of lactation by 186-478 kg, at the same time, milk quality indicators improved correspondingly. Thus, biological preparations PS-2 and Prevention-N-E are highly effective means of preventing obstetric and gynecological pathology.

scholarly journals Effect of cogon grass root ethanol extract on fatty acid binding protein 4 and oxidative stress markers in a sepsis mouse model

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Group 4 ◽  
Grass Root ◽  
Group 3 ◽  
Group 2 ◽  
And Oxidative Stress ◽  
Group 1

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, spleen, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant activity, FABP4 levels, and immune system-associated biomarker levels were also measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. Gpx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: Cogon grass root may aid in the development of herbal medicines and specific treatments for sepsis.

Abstract 11446: Systemic Administration of Mitochondria Alleviates 100% Oxygen-Induced Acute Respiratory Distress Syndrome in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hon Kan Yip ◽  
Tzu -Hsien Tsai ◽  
Steve Leu ◽  
Sarah Chua
Keyword(s):  
Oxidative Stress ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Ki 67 ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: We tested the hypothesis that mitochondria-replacement therapy ameliorated 100% oxygen-induced rat acute respiratory distress syndrome (ARDS). Methods and Results: Adult-Male SD rats (n=24) were equally categorized into group 1 (controls, room air inhalation), group 2 (ARDS: induced by inhalation of 100% oxygen for 48 hrs), and group 3 [ARDS + mitochondrial transfusion (1400 μg/each rat) from intra-venous administration 6 h after ARDS induction]. By 72 h after ARDS induction, the oxygen saturation (O 2 -Sat) was significantly lower in group 3 and more significantly lower in group 2 than in group 1, whereas pulmonary artery systolic-blood pressure showed a reversed pattern of O 2 -Sat among three groups (all p<0.001). H&E stain for lung crowded score showed an identical pattern of O 2 -Sat and number of alveolar sacs and lung weight exhibited an opposite pattern of O 2 -Sat among the three groups. The protein expressions of apoptotic (mitochondrial Bax, cleaved caspase 3 & PARP), fibrotic (Smad5, TGF-β), ROS (NOX-1, NOX-2, NOX-4), oxidative stress (oxidized protein), DNA- & mitochondrial-damaged (γ-H2AX, Ki-67; cytosolic cytochrome-c) and inflammatory (TNF-α, MMP-9, NF-κB) biomarkers, and IHC/IF microscopic findings of inflammatory (CD14+, CD68+), DNA-damaged (γ-H2AX+, Ki-67+) cells exhibited an opposite pattern, whereas the protein expressions of anti-apoptotic (Smad1/3, BMP-2) markers exhibited an identical pattern of O 2 -Sat among three groups (all p<0.001). The anti-oxidant (HO-2, NQO-1), mitochondrial-preserved (mitochondrial cytochrome-c) biomarkers, and cellular levels of anti-oxidants (HO-1, NQO-1, GR, GPx) were significantly higher in group 2 and more significantly higher in group 3 than in group 1 (all p<0.0001). Conclusions: Mitochondria therapy protects against 100% oxygen-induced ARDS. Key words: mitochondrial replacement, acute lung injury, inflammation, oxidative stress, DNA and mitochondrial damage

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