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 ◽  
...  

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.

2018 ◽  
Vol 103 (3-4) ◽  
pp. 139-148
Author(s):  
İlhan Bali ◽  
Fatin Rüştü Polat ◽  
Mehmet Aziret ◽  
Selim Sözen ◽  
Cem Oruç ◽  
...  

Objective: Anastomotic leaks are one of the chief complications after gastrointestinal surgery. The aim of this study was to evaluate whether Nigella sativa administration protects against ischemia/reperfusion injury on healing of colonic anastomosis in rats. Method: Thirty male Wistar albino rats, weighing between 200 and 240 g, were used in the study. They were randomly divided into three groups (n = 10 for each group): Anastomosis (group 1), anastomosis and ischemia/reperfusion injury (group 2), and treatment group of anastomosis, ischemia/reperfusion injury, and Nigella sativa (group 3). After 7 days, serum, plasma, and colonic tissue were obtained and then all rats were sacrificed. Tissue and serum level of total oxidant status, total antioxidant status, total thiol levels, hydroxyproline, interleukin-6, and TNF-alpha were determined and specimens were histopathologically evaluated. Results: In the Nigella sativa treated rats, serum hydroxyproline levels were significantly higher, while tissue levels were significantly lower than those seen in group 1 and group 2 (P = 0.007, P = 0.01, respectively). In the Nigella sativa group, the serum levels of TNF-α were significantly lower than those seen in group 1 and 2 (P = 0.001). Also, in group 3, the tissue IL-6 level was significantly higher than that seen in group 1 and group 2 (P = 0.009). The histopathologic analysis showed less edema and inflammatory cell infiltration in the Nigella sativa treated group, as well as a statistically significant difference according to the Chiu classification (P < 0.05). Conclusion: The results of this study indicate that Nigella sativa has a protective and therapeutic effect against ischemia/reperfusion injury on the healing of colonic anastomosis in rats.


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.


Medicina ◽  
2013 ◽  
Vol 49 (3) ◽  
pp. 19 ◽  
Author(s):  
Saban Yalcin ◽  
Turgay Ulas ◽  
Mehmet Eren ◽  
Harun Aydogan ◽  
Aysun Camuzcuoglu ◽  
...  

Background and Objective. Oxidative stress is believed to play a role in the development of preeclampsia (PE). It is known that an increased cystatin C level is also associated with PE. The aim of this study was to investigate the relationship between oxidative stress parameters and cystatin C levels in patients with severe PE. Material and Methods. Forty-four patients with severe PE and 40 healthy pregnant women were recruited for the study. All study subjects were divided into 2 groups: group 1 (n=44) consisted of patients with severe PE, and group 2 (n=40) included healthy pregnant subjects. Blood samples were obtained from all subjects in order to measure the cystatin C level, total antioxidant status, and total oxidant status. The oxidative stress index was calculated. Results. The group 1 had significantly higher cystatin C, total oxidant status, oxidative stress index levels and lower total antioxidant status level as compared with the group 2 (P=0.001, P<0.001, P<0.001, P=0.036, respectively). The serum cystatin C level was significantly correlated with the oxidative stress index (r=0.609, P<0.001). Conclusions. The present study demonstrated that both oxidative stress and cystatin C levels were increased in patients with PE, and the increased cystatin C levels seem to be a consequence of oxidative stress. Correspondence to


2021 ◽  
Vol 91 (1) ◽  
pp. 81-88
Author(s):  
Tolunay Kozlu ◽  
◽  
Fatma Güler ◽  
Pınar Peker Akalın ◽  
Filiz Kazak ◽  
...  

The effect of Theranekron® on rat ovaries was evaluated in healthy and ischemia-reperfusion injury models. The rats were divided into four groups: group 1: control, group 2: Theranekron® (single dose of 0.3 mg/kg intraperitoneally), group 3: torsion + detorsion, and group 4: torsion + detorsion + Theranekron® (single dose 0,3 mg/kg, intraperitoneally). The ovaries were homogenized by sonication before the analysis and supernatant glucose-6-phosphate dehydrogenase activity, reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione and total protein levels were evaluated spectrophotometrically. Ovary tissues were histologically examined. In group 2, glucose-6-phosphate dehydrogenase activity was significantly reduced (P<0.01) compared to the control group and an increased number of atretic follicles, and hyperaemic and haemorrhagic regions were seen histologically; in group 3, although glucose-6-phosphate dehydrogenase activity was not changed, intense hyperaemia and hemorrhage was observed in the veins of the medulla region and in the cortex. Group 4 showed a decrease in glucose-6-phosphate dehydrogenase activity compared to the control group (P<0.01). Histologically, when compared to group 3, group 4 showed fewer atretic follicles and decreased hyperaemia and hemorrhage in the ovaries, excluding the medulla region. There were no significant differences regarding reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate levels between the groups. The Theranekron® dose applied had some negative effects, such as reduced glucose-6-phosphate dehydrogenase activity, an increased number of atretic follicles, and hyperemia in the corpus luteum and medulla region in intact rat ovaries. Although it reduced glucose-6-phosphate dehydrogenase activity, Theranekron® may have had slight remedial effects on rat ovaries with ischemia-reperfusion injury.


2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Ilker Tekin ◽  
Meltem Demir ◽  
Sebahat Özdem

Abstract Background Ischemia–reperfusion injury of saphenous vein grafts (SVG) during coronary artery bypass grafting surgery negatively impacts endothelial integrity and functionality and is associated with vein graft failure. The aim of this study was to evaluate the level of oxidative stress in human SVG segments following ischemic storage in three intraoperative graft storage solutions: saline (S), autologous heparinized blood (HB) and DuraGraft (DG). Methods 3 mm tissue rings derived from surplus SVG segments from 50 patients were stored at room temperature for 30 min in DG, S or HB. Total oxidative status (TOS) and total antioxidant status (TAS) levels were determined from which the oxidative stress index (OSI: TOS/TAS ratio) was calculated. A p-value < 0.017 was considered significant implementing a Bonferroni correction. Results TOS values were significantly lower for DG stored samples in comparison to both S and HB; there was no difference between S and HB (DG: 32.6 ± 1.8, S: 39.6 ± 2.8 and HB: 40.6 ± 2.4 µmol H2O2 eqv.; DG vs. S and DG vs. HB p < 0.0001, S vs. HB p = 0.047). TAS was higher for both DG and HB in comparison to S (DG: 8.9 ± 0.9, S: 6.9 ± 1.0 and HB: 8.6 ± 0.9 mmol Trolox eqv.; DG vs S p < 0.0001, DG vs. HB p = 0.263, S vs. HB p < 0.0001). OSI differed between all groups with the lowest value for DG (DG: 3.7 ± 0.2, S: 5.8 ± 0.4 and HB: 4.7 ± 0.2 µmol H2O2 eqv./mmol Trolox eqv.; all p < 0.0001). Conclusions Saphenous veins grafts stored in DuraGraft had a lower oxidative level, higher antioxidant level and a lower oxidative stress index in comparison to saphenous vein grafts stored in saline or heparinized blood. ClinicalTrials.gov Identifier NCT02922088.


2013 ◽  
pp. 681-690 ◽  
Author(s):  
F. T. HAMMAD ◽  
S. AL-SALAM ◽  
L. LUBBAD

The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28±0.36 vs. 0.39±0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18±0.05 vs. 0.10±0.02, P=0.07). The left renal FENa was significantly lower in Group-2 (29.9±6.4 vs. 49.7±7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, and fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.


1994 ◽  
Vol 267 (6) ◽  
pp. H2204-H2212 ◽  
Author(s):  
B. Friesenecker ◽  
A. G. Tsai ◽  
M. Instaglietta

Ischemia-reperfusion injury was investigated in terms of functional capillary density (FCD), capillary red blood cell velocity (cRBCv), and arteriolar and venular diameter after 4-h ischemia in the unanesthetized hamster skin-fold preparation. Animals in group 1 were studied by transillumination. Group 2 received a bolus injection of fluorescein isothiocyanate (FITC)-dextran (mol wt 150,000) and was studied by transillumination (zone 1) and epi-illumination (zone 2). In group 1, FCD decreased after ischemia (92% of baseline, 30 min), returning to control up to 24 h. cRBCv increased after reperfusion, being 175% of baseline at 24 h. Arterioles and venules dilated for 24 h after reperfusion. In group 2/zone 2, FCD progressively decreased to 11% of control, arteriolar dilation was inhibited, and cRBCv increased 30 min and 2 h after reperfusion. Tissue perfusion index (FCD x cRBCv) increased 158% in group 1 at 24 h, did not change in group 2/zone 1, and was 9% of control at 24 h in group 2/zone 2 (P < or = 0.05). We conclude that increased perfusion is a normal reaction to ischemia-reperfusion injury in this model, and previously observed capillary no reflow is due to FITC-dextran phototoxicity.


Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 417
Author(s):  
Karol Tejchman ◽  
Adam Nowacki ◽  
Katarzyna Kotfis ◽  
Edyta Skwirczynska ◽  
Maciej Kotowski ◽  
...  

Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and ET-3), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) during the reperfusion of human kidneys grafted from brain dead donors and later transplanted. The study group (n = 44) was analyzed according to the method of kidney storage: Group 1 underwent hypothermic machine perfusion (HMP) in the LifePort perfusion pump (n = 22), and Group 2 underwent static cold storage (SCS) (n = 22). The analysis of kidney function was performed daily during the first seven days after transplantation. The kidneys in Group 1 were characterized by higher absolute concentrations of ET-1, IL-18, and NGAL, as well as a lower concentration of ET-2 (p = 0.017) and ET-3. The relative increase of ET-1 (p = 0.033), ET-2, and ET-3 during reperfusion was lower in this group, while the relative decrease of NGAL was higher. Group 1 was also characterized by significant decrease of IL-18 (p = 0.026) and a tendency for better kidney function based on the higher total diuresis, higher glomerular filtration rate (GFR), higher potassium level, lower serum creatinine, and lower urea concentration during the seven-day postoperative observation period. The long-term beneficial impact of hypothermic machine perfusion on the outcome of transplanted kidneys may rely on the early modified proceedings and intensity of ischemia-reperfusion injury reflected by the dynamics of the concentrations of examined biomarkers.


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.


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