Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases that occur in individuals who do not consume a significant amount of alcohol, and the pathogenesis of NAFLD remains undefined. It was aimed to investigate whether the use of Trimetazidine (TMZ) could reduce warm ischemia-reperfusion (I/R) damage after liver ischemia on an experimental NAFLD model in this experimental study. Methods: For this aim, Sprague Dawley male rats were separated into 4 groups; control group (group 1, n = 6), sham operated control grup (group 2, n = 6), warm ischemia/reperfusion group (group 3, n=10), and TMZ group (group 4, n=10, administration of TMZ (10 mg/kg) 30-min before fatty liver I/R). The serum oxidant and antioxidant biochemical markers were measured by ELISA methods. The histopathological evaluation was also performed in the hepatocytes. Results: TMZ was caused to significantly decrease on oxidative stress markers levels which characterized myeloperoxidase (MPO) (p<0.001), nicotinamide adenine dinucleotide phosphate-oxidase (NOX) (p<0.001), and cytochrome C (Cyt-C) (p<0.001), and increase on antioxidant enzyme catalase (CAT) (p<0.001) activity as compared to group 3. However, TMZ was no caused to any significant change in other oxidant markers malondialdehyde (MDA) and 8-hydroxyguanosine (8-OHDG) levels (p> 0.05). While hepatocyte damage as a form of cell groups was observed due to I/R damage, whereas TMZ had caused positive improvements on dilatation of sinusoids, inflammation and the structural integrity of hepatic plaques. Conclusion: Trimetazidine could be positively contributing effects to the antioxidant defense mechanism and also the survival of cells by protecting mitochondrial integrity.

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The influence of Theranekron® on glucose-6-phosphate dehydrogenase activity in rat ovaries, intact and with ischemia-reperfusion injury

Veterinarski arhiv ◽

10.24099/vet.arhiv.0828 ◽

2021 ◽

Vol 91 (1) ◽

pp. 81-88

Author(s):

Tolunay Kozlu ◽

◽

Fatma Güler ◽

Pınar Peker Akalın ◽

Filiz Kazak ◽

...

Keyword(s):

Reperfusion Injury ◽

Dehydrogenase Activity ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Control Group ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Glucose 6 Phosphate Dehydrogenase

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.

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Effects of Nitroglycerine on Renal Ischemia-Reperfusion Injury in Adult Male Rats

Drug Research ◽

10.1055/a-0958-1987 ◽

2019 ◽

Vol 69 (11) ◽

pp. 612-620

Author(s):

Fatemeh Ahmadi ◽

Saeed Hajihashemi ◽

Ali Rahbari ◽

Fatemeh Ghanbari

Keyword(s):

Lipid Peroxidation ◽

Defense Mechanism ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Blood Flow Rate ◽

Renal Tissue ◽

Male Rats ◽

Control Group ◽

Protective Effects

Abstract Background Ischemia-reperfusion (I-R) leads to acute kidney injury (AKI). The present study investigated the effects of nitroglycerine (NG) on improving renal dysfunctions caused by I-R in rats. Methodology Twenty-four rats were equally divided into four groups: (1) the control group, (2) the sham group, (3) the I-R group, and (4) NG-treated groups.NG (50 μg/kg) was injected intraperitoneally after induction of IR. I-R was induced through clamping of the bilateral renal artery and vein of both kidneys for 20 min followed by 24 h of reperfusion. Results NG significantly increased the creatinine clearance levels and renal blood flow rate (which was reduced by I-R). NG also significantly improved serum electrolytes (sodium and potassium) that were disordered by I-R. In addition, NG significantly offset impaired antioxidant defense mechanism and inhibited lipid peroxidation. Conclusions The results show NG has a protective effect on renal tissue against AKI caused by I-R. These protective effects mediated through antioxidant activity and decrease of lipid peroxidation.

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Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3861914 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Zhongzhong Liu ◽

Xingjian Zhang ◽

Qi Xiao ◽

Shaojun Ye ◽

Chin-Hui Lai ◽

...

Keyword(s):

Reperfusion Injury ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Isolated Perfused Rat Liver ◽

Enzyme Release ◽

Circulatory Death ◽

Dependent Mechanism

Objective. Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism. Methods. 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion. Results. Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group. Conclusion. Pretreatment of DCD donors with simvastatin improves DCD livers’ functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.

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Biopolymeric Modification of Superoxide Dismutase (mPEG-SOD) to Prevent Muscular Ischemia-Reperfusion Damage

The International Journal of Artificial Organs ◽

10.1177/039139889501800309 ◽

1995 ◽

Vol 18 (3) ◽

pp. 167-172 ◽

Cited By ~ 9

Author(s):

R. Giardino ◽

S. Capelli ◽

M. Fini ◽

G. Giavaresi ◽

L. Orienti ◽

...

Keyword(s):

Superoxide Dismutase ◽

Ischemia Reperfusion Injury ◽

Clinical Course ◽

Ischemia Reperfusion ◽

Warm Ischemia ◽

Control Group ◽

Acute Ischemia ◽

Time Intervals ◽

Doppler Flowmetry ◽

Reperfusion Damage

The efficacy of preventing ischemia-reperfusion damage by employing native or modified (mPEG-SOD) superoxide dismutase in an experimental animal model of acute ischemia of the left hindlimb was tested. Four hours and thirty minutes complete warm ischemia was induced in the left hindlimb of 43 Wistar rats, by clamping the femoral artery and monitoring its efficacy with Laser Doppler flowmetry. After ten days, a significative difference (p=0.004) of the survival leg rate was found in the group treated with mPEG-SOD (86.6%) compared with the control group (30%). Histomorphological and ultrastructural analysis were performed at different time intervals confirming what the clinical course had already pointed out. These results show that SOD in its modified form, despite the lower dosage, can provide good protection against ischemia/reperfusion injury of muscles.

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Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502008000700006 ◽

2008 ◽

Vol 23 (suppl 1) ◽

pp. 31-35 ◽

Cited By ~ 6

Author(s):

Silvio Tucci Jr ◽

Carlos Augusto Fernandes Molina ◽

Adauto José Cologna ◽

Haylton Jorge Suaid ◽

Luis Fernando Tirapelli ◽

...

Keyword(s):

Reperfusion Injury ◽

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Dry Weight ◽

Warm Ischemia ◽

Unilateral Nephrectomy ◽

Control Group ◽

Compensatory Renal Growth

PURPOSE: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR) and mitochondrial function. METHODS: Forty five Wistar rats were divided in 3 groups: Control Group (GC) - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats) and 7th (15 rats) postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats) and to quantify mitochondrial respiration (9 rats); Group 1 (G1) - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats) and dry weight (6 rats). Group 2 (G2) - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats) and dry weight (6 rats). RESULTS: Dry weight (mg) of left kidneys at 7th day: GC - 219±18, G1 - 281±23 and G2 - 338±39 (GCxG1 p<0.01; GCxG2 p<0.001; G1xG2 p<0.01). State 4 mitochondrial respiration rate and respiratory control ratio (RCR) were similar in all groups (p>0.05). State 3 respirations (mM/min/mg) in GC, G1 and G2 was respectively: 99±23, 132±22 and 82±44 (p<0.02; the only statistical difference noted was between groups G1xG2 - p<0.05). CONCLUSIONS: Following unilateral nephrectomy CRG is associated with an increase in state 3 of mitochondrial respiration. Renal ischemia/reperfusion injury enhances the CRG provoked by unilateral nephrectomy but such enhancement seems independent on mitochondrial respiration.

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Metabolites of Tryptophane and Phenylalanine as Markers of Small Bowel Ischemia-Reperfusion Injury

Open Chemistry ◽

10.1515/chem-2018-0076 ◽

2018 ◽

Vol 16 (1) ◽

pp. 709-715

Author(s):

Jana Mašlanková ◽

Štefan Tóth ◽

Vladimíra Tomečková ◽

Tímea Tóth ◽

Matan Katz ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Serotonin Level ◽

Vanillylmandelic Acid ◽

Ischemic Reperfusion Injury ◽

Ischemic Reperfusion ◽

Hydroxyindoleacetic Acid

AbstractIschemic-reperfusion injury of the small intestine is an acute clinical condition with high mortality rate. This study describes the changes in levels of phenylalanine and tryptophan metabolites in intestinal homogenates and urine samples of Wistar male rats after 60 minutes of mesenteric ischemia and different reperfusion periods (1, 24, 30 hours) in comparison with a control group without the ischemia. The ischemic-reperfusion injury was quantified by the histopathological injury index. The levels of serotonin, epinephrine, and norepinephrine were determined in the intestinal homogenate and epinephrine, vanillylmandelic acid, and the 5-hydroxyindoleacetic acid was analyzed in urine using the HPLC method. The statistically significant increased level of serotonin, epinephrine and norepinephrine were detected in the intestinal samples after 24 hours of reperfusion (p<0.01); even the most elevated serotonin level was observed after one hour of reperfusion (p<0.001). A statistically significant decreased level of vanillylmandelic acid was observed after one hour of reperfusion, but it significantly increased after 24 hours (p<0.05) in urine. The elevated level of the 5-hydroxyindoleacetic acid after one hour and 24 hours after reperfusion (p<0.05) were determined in the urine. The most significant elevated epinephrine level was observed after 24 hours of reperfusion (p<0.001) in urine. Results showed a potential role of serotonin as an early biomarker (after one hour of reperfusion) of small intestinal damaged homogenate, while the best predictor of intestinal injury in urine was epinephrine, which was elevated after 24 hours.

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Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia

International Journal of Molecular Sciences ◽

10.3390/ijms22168373 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8373

Author(s):

Viktorija Zitkute ◽

Mindaugas Kvietkauskas ◽

Vygante Maskoliunaite ◽

Bettina Leber ◽

Diana Ramasauskaite ◽

...

Keyword(s):

Reperfusion Injury ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Combined Treatment ◽

Warm Ischemia ◽

Control Group ◽

Protective Effects ◽

Sprague Dawley

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.

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Opioid Preconditioning Modulates Repair Responses to Prevent Renal Ischemia-Reperfusion Injury

Pharmaceuticals ◽

10.3390/ph13110387 ◽

2020 ◽

Vol 13 (11) ◽

pp. 387

Author(s):

Adriana Franco-Acevedo ◽

Raquel Echavarria ◽

Bibiana Moreno-Carranza ◽

Cesar-Ivan Ortiz ◽

David Garcia ◽

...

Keyword(s):

Renal Function ◽

Reperfusion Injury ◽

Tissue Repair ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Vegf Receptor ◽

Renal Hilum ◽

Pharmacological Preconditioning

Progression to renal damage by ischemia-reperfusion injury (IRI) is the result of the dysregulation of various tissue damage repair mechanisms. Anesthetic preconditioning with opioids has been shown to be beneficial in myocardial IRI models. Our main objective was to analyze the influence of pharmacological preconditioning with opioids in renal function and expression of molecules involved in tissue repair and angiogenesis. Experimental protocol includes male rats with 45 min ischemia occluding the left renal hilum followed by 24 h of reperfusion with or without 60 min preconditioning with morphine/fentanyl. We analyzed serum creatinine and renal KIM-1 expression. We measured circulating and intrarenal VEGF. Immunohistochemistry for HIF-1 and Cathepsin D (CTD) and real-time PCR for angiogenic genes HIF-1α, VEGF, VEGF Receptor 2 (VEGF-R2), CTD, CD31 and IL-6 were performed. These molecules are considered important effectors of tissue repair responses mediated by the development of new blood vessels. We observed a decrease in acute renal injury mediated by pharmacological preconditioning with opioids. Renal function in opioid preconditioning groups was like in the sham control group. Both anesthetics modulated the expression of HIF-1, VEGF, VEGF-R2 and CD31. Preconditioning negatively regulated CTD. Opioid preconditioning decreased injury through modulation of angiogenic molecule expression. These are factors to consider when establishing strategies in pathophysiological and surgical processes.

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The cardioprotective potential of Tadalafil in myocardial ischemia/reperfusion

American Journal of BioMedicine ◽

10.18081/2333-5106/020-2/87-100 ◽

2020 ◽

Vol 8 (2) ◽

pp. 87-100

Author(s):

Najah R. Hadi ◽

Fadhil G. Al-Amran

Keyword(s):

Myocardial Ischemia ◽

Caspase 3 ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Male Rats ◽

Control Group ◽

Inflammatory Reactions ◽

Tnf Α ◽

Myocardial Ischemia Reperfusion

The objective of this study is to assess the potential protective effect of Tadalafil on myocardial ischemia reperfusion injury induced by LAD ligation, 28 male rats were randomized into 4 groups (7 rats per group); Sham, rats underwent the same anesthetic and surgical procedure except for LAD ligation; control, rats underwent LAD ligation for 30 minutes and reperfusion for 2 hours; vehicle, rats treated with 10% DMSO, the Tadalafil solvent 30 minutes before the ligation; Tadalafil group, rats pretreated with Tadalafil1mg/kg i.p 30 minutes before ligation. In control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P<0.05), while serum GSH significantly decreased (P<0.05). Histopathologically, control group showed a significant cardiac injury (P<0.05) compared with sham group. Tadalafil significantly counteracted (P<0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Tadalafil produces a significant elevation (P<0.05) in cardiac IL-10 and serum GSH with significant reduction in (P<0.05) cardiac injury. In We concluded that Tadalafil attenuates myocardial I/R injury in male rats through interfering with inflammatory reactions and apoptosis .

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