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 ◽  
...  

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.

2020 ◽  
Vol 50 (6) ◽  
pp. 1513-1522
Author(s):  
Şenol KALYONCU ◽  
Bülent YILMAZ ◽  
Mustafa DEMİR ◽  
Meltem TUNCER ◽  
Zehra BOZDAĞ ◽  
...  

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.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  

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.


2019 ◽  
Vol 65 (9) ◽  
pp. 1193-1200
Author(s):  
Orhan Fındık ◽  
Melda Yardımoglu Yılmaz ◽  
Yusufhan Yazır ◽  
Selenay Furat Rençber ◽  
Kübra Kavram Sarıhan ◽  
...  

SUMMARY OBJECTIVES This study was conducted to reveal the possible protective effects of ticagrelor and enoxaparin pretreatment against ischemia-reperfusion (IR)-induced injury on the lung tissue of a rat model. METHODS Wistar albino rats were randomly divided into 4 groups as follows: group-1 (control-sham), group-2 (control-saline+IR), group-3 (ticagrelor+IR), group-4 (enoxaparin+IR). Before the ischemic period, saline, ticagrelor, and enoxaparin were administered to the 2nd-4th groups, respectively. In these groups, IR injury was induced by clamping the aorta infrarenally for 2 h, followed by 4 h of reperfusion except group-1. After the rats were euthanized, the lungs were processed for histological examinations. Paraffin sections were stained with Haematoxylin&Eosin (H&E) for light microscopic observation. Apoptosis was evaluated by caspase-3 immunoreactivity. Data were statistically analyzed using the SPSS software. RESULTS In the lung sections stained with H&E, a normal histological structure was observed in group-1, whereas disorganized epithelial cells, hemorrhage, and inflammatory cell infiltration were seen in the alveolar wall in group-2. The histologic structure of the treatment groups was better than that of group-2. Caspase-3(+) apoptotic cells were noticeable in sections of group-2 and were lower in the treatment groups. In group-4, caspase-3 immunostaining was lower than in group-3. In group-2, apoptotic cells were significantly higher than in the other groups (p<0.001). CONCLUSION Based on the histological results, we suggested that both therapies ameliorated the detrimental effects of IR. Caspase-3 immunohistochemistry results also revealed that pre-treatment with enoxaparin gave better results in an IR-induced rat injury model. In further studies, other parameters such as ROS and inflammatory gene expressions should be evaluated for accurate results.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Osman Tiryakioglu ◽  
Kamuran Erkoc ◽  
Bulent Tunerir ◽  
Onur Uysal ◽  
H. Firat Altin ◽  
...  

Objective. The objective of this study was to examine the effects of iloprost and N-acetylcysteine (NAC) on ischemia-reperfusion (IR) injuries to the gastrocnemius muscle, following the occlusion-reperfusion period in the abdominal aorta of rats.Materials and Methods. Forty male Sprague-Dawley rats were randomly divided into four equal groups.Group 1: control group. Group 2 (IR): aorta was occluded. The clamp was removed after 1 hour of ischemia. Blood samples and muscle tissue specimens were collected following a 2-hour reperfusion period.Group 3 (IR + iloprost): during a 1-hour ischemia period, iloprost infusion was initiated from the jugular catheter. During a 2-hour reperfusion period, the iloprost infusion continued.Group 4 (IR + NAC): similar to the iloprost group.Findings. The mean total oxidant status, CK, and LDH levels were highest in Group 2 and lowest in Group 1. The levels of these parameters in Group 3 and Group 4 were lower compared to Group 2 and higher compared to Group 1 (P<0.05). The histopathological examination showed that Group 3 and Group 4, compared to Group 2, had preserved appearance with respect to hemorrhage, necrosis, loss of nuclei, infiltration, and similar parameters.Conclusion. Iloprost and NAC are effective against ischemia-reperfusion injury and decrease ischemia-related tissue injury.


2020 ◽  
Vol 55 (1) ◽  
pp. 11-17
Author(s):  
Ömer Faruk Gülaştı ◽  
Şadan Yavuz ◽  
Ali Ahmet Arıkan ◽  
Fatma Ceyla Eraldemir ◽  
Ersan Özbudak ◽  
...  

Introduction: Naftidrofuryl and cilostazol are drugs with proven efficacy in the treatment of claudication in peripheral vascular disease. In this experimental study, we evaluated the effects of naftidrofuryl and cilostazol in ischemia-reperfusion (IR) injury on various tissues. Materials and Methods: 40 male albino Wistar rats (8-12 weeks old, 250-350 g.) are randomly divided into 4 groups: Control (Group 1), sham (group 2), cilostazol pre-treatment (group 3), naftidrofuryl pre-treatment (group 4). During 21 days placebo is given to group 2, 12 mg/kg/day cilostazol is given to group 3, 50 mg/kg/day naftidrofuryl is given to group 4 orally. Ischemia and reperfusion are induced at the lower hind limb in Groups 2, 3 and 4. Ischemic muscle, kidney, liver, heart, brain and blood samples are obtained. The total antioxidant capacity, oxidant levels and oxidative stress index are studied for each group. Results: Both drugs have protective effects of remote organ injury following IR. Systemic effects are similar to each other, both have protective effects of IR injury. It showed no statistical significance in the total antioxidant capacity. Total oxidant levels are significantly affected by cilostazol in the heart (p < 0.01) and by naftidrofuryl in the liver (p < 0.01). The effect on oxidative stress was only significant with cilostazol on the heart (p < 0.01). Conclusion: Cilostazol and naftidrofuryl had beneficial effects in all tissues against tissue damage caused by IR injury. In ischemic muscle, kidney and heart cilostazol had improved outcomes comparing to naftidrofuryl. Naftidrofuryl had benefits over cilostazol in liver tissue.


2019 ◽  
Vol 18 (2) ◽  
pp. 149-155
Author(s):  
David Calderón Guzmán ◽  
Norma Osnaya Brizuela ◽  
Maribel Ortíz Herrera ◽  
Hugo Juárez Olguín ◽  
Armando Valenzuela Peraza ◽  
...  

Background & Objective: The purpose of this study was to measure the effect on brain biomarkers after treatment with anticancer compounds - cytarabine (CT) and ferric carboxymaltose (FC) (Fe+3) in Wistar rats. Methods: The Wistar rats were treated as follows: group 1 (control), NaCl 0.9%; group 2, CT (25 mg/k), group 3, FC(Fe+3) (50 mg/k) and group 4, CT + FC(Fe+3). The animals were sacrificed and their brains were obtained and used to measure lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolite (5-HIAA) and dopamine. The results indicated an enhancement of lipid peroxidation in the cortex and striatum of groups treated with FC(Fe+3) and CT, while GSH decreased in the cortex of group treated with CT + FC(Fe+3). Dopamine decreased in the cortex of the rats that received CT, while in the striatum, 5HIAA increased in all groups. </P><P> Results & Conclusion: These results suggest that the treatment with CT and FC(Fe+3) boosted oxidative stress and led to an alteration in momoamine concentrations in the brain.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  

  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.


2021 ◽  
pp. 197140092098356
Author(s):  
Marwan Alkrenawi ◽  
Michael Osherov ◽  
Azaria Simonovich ◽  
Jonathan Droujin ◽  
Ron Milo ◽  
...  

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.


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