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

scholarly journals Continuation or Discontinuation of Statin Therapy Did Not Influence Patient Outcomes after the Development of Acute Respiratory Distress Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Seth R. Bauer ◽  
Simon W. Lam ◽  
Anita J. Reddy
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Statin Therapy ◽  
Distress Syndrome ◽  
Tertiary Care ◽  
Diagnosis Group ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background. The anti-inflammatory effects of statin therapy may be beneficial in the treatment and prevention of acute respiratory distress syndrome (ARDS). Objectives. Determine if continuation or discontinuation of prior statin therapy is associated with ventilator-free days (VFDs) at day 28 in patients with ARDS. Methods. Patients with ARDS admitted to the intensive care units of a tertiary care medical center were evaluated in this retrospective cohort study. Included patients were allocated to three groups: patients in whom statin therapy was given before and continued after ARDS diagnosis (Group 1), patients with statin therapy only before ARDS diagnosis (Group 2), and patients never exposed to statins (Group 3). Results. Of 244 patients evaluated, 187 were included; 17 (9.1%) patients in Group 1, 20 (10.7%) in Group 2, and 150 in Group 3. There were no differences among groups in APACHE II or SOFA scores. VFDs were not significantly different among groups (median 0 versus 4.5 versus 13.5 days, P=0.21). After adjustment for baseline characteristics, including propensity for statin administration, statin therapy was not associated with increased VFDs on linear regression. Conclusions. Exposure to statins before or after ARDS diagnosis was not associated with improved VFDs in this cohort of patients with ARDS.

scholarly journals Cellular Prion Protein Is Essential for Myocardial Regeneration but Not the Recovery of Left Ventricular Function from Apical Ballooning

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 167
Author(s):  
Jiunn-Jye Sheu ◽  
Han-Tan Chai ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
Yi-Ling Chen ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Cell Stress ◽  
Cellular Prion Protein ◽  
Myocardial Regeneration ◽  
Stress Signaling ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.

scholarly journals Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Cheuk-Kwan Sun ◽  
Yen-Yi Zhen ◽  
Hung-I Lu ◽  
Pei-Hsun Sung ◽  
Li-Teh Chang ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Similar Pattern ◽  
Sirna Delivery ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.

scholarly journals on some aspects of furosemide routine prescription at acute respiratory distress syndrome at the prehospital stage

2016 ◽  
Vol 1 (5) ◽  
pp. 15-18
Author(s):  
Горбачёва ◽  
Svetlana Gorbacheva ◽  
Дац ◽  
Andrey Dats ◽  
Дац ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Survival Rate ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Organ Dysfunction ◽  
Mortality Risk ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
Group 2 ◽  
Group 1

We studied the effect of furosemide application at the pre-hospital stage on survival rate and mortality risk in patients with acute respiratory distress syndrome. It was found that out of 665 patients admitted to intensive care units, 90 have been diagnosed with acute respiratory distress syndrome, of which 75 have noted decreased preload. Those patients were divided into two groups: group 1 (n = 28) received furosemide on the first day, group 2 (n = 47) did not receive furosemide. The patients of both groups matched by age, the severity of the condition and the severity of organ dysfunction. The 10-day survival rate in the patients with acute respiratory distress syndrome and reduced preload received furosemide at the pre-hospital stage made 11 % and was significantly lower than in the patients without furosemide– 43 % (p = 0.031). The frequency of multiple organ dysfunction syndrome in group 1 the was statistically higher than in patients without furosemide (93 % and 75 % respectively; p = 0.048). Furosemide admin-istration in patients with acute respiratory distress syndrome and reduced preload 1.8 times increases the relative mortality risk (p = 0.032).

Thyroid Hormone and Thyrotropin Responses to Parturition in Premature Infants With and Without the Respiratory Distress Syndrome

PEDIATRICS ◽  
1979 ◽  
Vol 63 (3) ◽  
pp. 380-385
Author(s):  
Alan H. Klein ◽  
Barbara Foley ◽  
Frederic M. Kenny ◽  
Delbert A. Fisher
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Premature Infants ◽  
Distress Syndrome ◽  
Mean Value ◽  
Term Infants ◽  
Serum T4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyrotropin (TSH), and thyroxine-binding globulin (TBG) concentrations were measured in well full-term infants (group 1), well premature infants (group 2), and premature infants with the respiratory distress syndrome (group 3). Samples were collected at birth and at 2, 12, and 24 hours after delivery. Significant increases in mean serum TSH concentrations occurred in all three groups two hours after delivery, but the two-hour levels measured in groups 2 and 3 were less than those in group 1 infants. Serum T4 concentrations increased significantly after delivery in groups 1 and 2 but not in group 3 newborns; mean TBG concentrations did not vary significantly in any of the groups. Serum T4, concentrations increased significantly at two hours in all three groups but were significantly depressed at 12 and 24 hours in group 3 infants. Mean serum rT3, concentrations decreased after birth in group 2 and 3 in contrast to group 1 newborns; the mean value increased significantly between 2 and 24 hours in group 3 infants. The pattern of decreasing senrum T3 and increasing rT3 concentrations in group 3 infants between 2 and 24 hours resembles the pattern of change in triiodothyronines in ill adult patients, which suggests that these variations are due primarily to illness and not to prematurity.

scholarly journals Combined melatonin-adipose derived mesenchymal stem cell therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury

2021 ◽  
Author(s):  
Yen‐Ta Chen ◽  
Fei-Chi Chuang ◽  
Chih‐Chao Yang ◽  
John Y. Chiang ◽  
Pei‐Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Testicular Torsion ◽  
Ischemia Reperfusion ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Background: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cell (ADMSC) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and Results: Male-adult SD rats (n=30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720 degrees counterclockwisely for 2h, then detorsion (i.e., reperfusion) to the original position for 72h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 minutes after ischemia, followed by 20 mg at 3h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSC/1.2 x 106 cells/intravenous administration at 30 minutes after ischemia, followed by days 1/2 TTIR) and group 5 (TTIR + Mel + ADMSC). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C) and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2 and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p<0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p<0.0001).Conclusion: Mel-ADMSCs effectively protected the testis against TTIR injury.

scholarly journals Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yen-Ta Chen ◽  
Fei-Chi Chuang ◽  
Chih-Chao Yang ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Testicular Torsion ◽  
Ischemia Reperfusion ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Background This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. Methods and results Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). Conclusion Mel-ADMSCs effectively protected the testis against TTIR injury.

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 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.

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