scholarly journals Protective Effect of Water-Soluble C60 Fullerene Nanoparticles on the Ischemia-Reperfusion Injury of the Muscle Soleus in Rats

2021 ◽  
Vol 22 (13) ◽  
pp. 6812
Author(s):  
Dmytro Nozdrenko ◽  
Tetiana Matvienko ◽  
Oksana Vygovska ◽  
Kateryna Bogutska ◽  
Olexandr Motuziuk ◽  
...  

The biomechanical parameters of muscle soleus contraction in rats and their blood biochemical indicators after the intramuscular administration of water-soluble C60 fullerene at doses of 0.5, 1, and 2 mg/kg 1 h before the onset of muscle ischemia were investigated. In particular, changes in the contraction force of the ischemic muscle soleus, the integrated power of the muscle, the time to achieve the maximum force response, the dynamics of fatigue processes, and the parameters of the transition from dentate to smooth tetanus, levels of creatinine, creatine kinase, lactate and lactate dehydrogenase, and parameters of prooxidant–antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, and reduced glutathione and catalase) were analyzed. The positive therapeutic changes in the studied biomechanical and biochemical markers were revealed, which indicate the possibility of using water-soluble C60 fullerenes as effective prophylactic nanoagents to reduce the severity of pathological conditions of the muscular system caused by ischemic damage to skeletal muscles.

2021 ◽  
Vol 22 (9) ◽  
pp. 4977
Author(s):  
Dmytro Nozdrenko ◽  
Olga Abramchuk ◽  
Svitlana Prylutska ◽  
Oksana Vygovska ◽  
Vasil Soroca ◽  
...  

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 μg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40–45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55–65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.


2005 ◽  
Vol 83 (6) ◽  
pp. 483-492 ◽  
Author(s):  
Eman El Eter ◽  
Hanan H Hagar ◽  
Ali Al-Tuwaijiri ◽  
Maha Arafa

Pyrrolidinedithiocarbamate (PDTC) is a potent antioxidant and an inhibitor of nuclear factor-κB (NF-κB). The present study examined the impact of PDTC preconditioning on gastric protection in response to ischemia-reperfusion (I/R) injury to the rat stomach. Male Wistar rats were recruited and divided into 3 groups (n=7). One group was subjected to gastric ischemia for 30 min and reperfusion for 1 hour. The second group of rats was preconditioned with PDTC (200 mg/kg body mass i.v.) 15 min prior to ischemia and before reperfusion. The third group of rats was sham-operated and served as the control group. Gastric I/R injury increased serum lactate dehydrogenase level, vascular permeability of gastric mucosa (as indicated by Evans blue dye extravasation) and gastric content of inflammatory cytokine; tumor necrosis factor-α (TNF-α). Moreover, oxidative stress was increased as indicated by elevated lipid peroxides formation (measured as thiobarbituric acid reactive substances) and depleted reduced glutathione in gastric tissues. NF-κB translocation was also detected by electrophoretic mobility shift assay. Microscopically, gastric tissues subjected to I/R injury showed ulceration, hemorrhages, and neutrophil infiltration. Immunohistochemical studies of gastric sections revealed increased expression of p53 and Bcl-2 proteins. PDTC pretreatment reduced Evans blue extravasation, serum lactate dehydrogenase levels, gastric TNF-α levels, and thiobarbituric acid reactive substances content, and increased gastric glutathione content. Moreover, PDTC pretreatment abolished p53 expression and inhibited NF-κB translocation. Finally, histopathological changes were nearly restored by PDTC pretreatment. These results clearly demonstrate that NF-κB activation and pro-apoptotic protein p53 induction are involved in gastric I/R injury. PDTC protects against gastric I/R injury by an antioxidant, NF-κB inhibition, and by reduction of pro-apoptotic protein p53 expression, which seems to be downstream to NF-κB, thus promoting cell survival. Key words: pyrrolidinedithiocarbamate, ischemia–reperfusion injury, gastric mucosa, nuclear factor-κB, inflammatory cytokines, oxidative stress.


2004 ◽  
Vol 286 (5) ◽  
pp. H1649-H1653 ◽  
Author(s):  
Yiru Guo ◽  
Adam B. Stein ◽  
Wen-Jian Wu ◽  
Wei Tan ◽  
Xiaoping Zhu ◽  
...  

Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 ± 3.5% vs. 36.5 ± 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 ± 4.9% of the region at risk ( n = 13) vs. 47.7 ± 3.8% ( n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.


2020 ◽  
Vol 21 (16) ◽  
pp. 5703 ◽  
Author(s):  
Arnau Panisello Rosello ◽  
Rui Teixeira da Silva ◽  
Carlos Castro ◽  
Raquel G. Bardallo ◽  
Maria Calvo ◽  
...  

Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Raquel Lopez Diez ◽  
Qing Li ◽  
Huilin Li ◽  
Shi Fang Yan ◽  
Ann Marie Schmidt

Peripheral vascular disease is a condition characterized by atherosclerotic narrowed arteries distal to the aorta which triggers an acute or critical limb ischemia. Development of ischemic PVD has been considered one of the principal complications of diabetes, leading to amputation of digits and limbs. Advanced glycation end products (AGE) ligands and their receptor (RAGE) have been implicated in multiple key mechanisms underlying diabetes and diabetic complications, including hypoxia and ischemia/reperfusion injury. We tested the hypothesis that vascular recovery after hind limb ischemia would be rescued by deficiency of RAGE, at least in part through modulation of macrophage dysfunction. Wild type (WT) and Ager deficient mice were rendered diabetic with streptozotocin, and subjected to unilateral hind limb ischemia. Previous results showed an increased accumulation and expression of AGEs and RAGE in ischemic muscle, especially in diabetic WT mice. Attenuated angiogenesis and impaired blood flow recovery were also observed, in parallel with reduced early inflammatory macrophage infiltration into ischemic muscle in the WT diabetic mice. We performed flow cytometry to analyze circulating monocyte subsets: pro-inflammatory Ly6G/C hi and anti-inflammatory Ly6G/C lo . Work by others reported higher levels of monocytes in diabetes in the baseline state without injury; our data indicate that the increase is mostly attributed to the pro-inflammatory Ly6G/C hi population, being significantly lower in the Ager -/- diabetic mice. After seven days of ischemia to the unilateral hind limb, lower levels of circulating pro-inflammatory Ly6G/C hi monocytes were found in both WT and Ager deficient diabetic mice. After four weeks of injury, the pro-inflammatory monocytes levels were significantly recovered to baseline levels in Ager -/- mice, whereas WT mice failed to reacquire their baseline levels. In vitro studies using murine endothelial cells and murine macrophages revealed that RAGE suppressed macrophage-endothelial cell interaction, particularly in diabetes-relevant concentrations of D-glucose. These data suggest unique ischemia-dependent mechanisms in hind limb ischemia through RAGE down-regulation of the early adaptive immune response.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed Bejaoui ◽  
Eirini Pantazi ◽  
Maria Calvo ◽  
Emma Folch-Puy ◽  
Anna Serafín ◽  
...  

Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proven their effectiveness in variousin vivoandin vitromodels of tissue injury. The present study aims to investigate whether the intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) could be an effective strategy for rat liver preconditioning against IRI. PEG 35 was intravenously administered at 2 and 10 mg/kg to male Sprague Dawley rats. Then, rats were subjected to one hour of partial ischemia (70%) followed by two hours of reperfusion. The results demonstrated that PEG 35 injected intravenously at 10 mg/kg protected efficiently rat liver against the deleterious effects of IRI. This was evidenced by the significant decrease in transaminases levels and the better preservation of mitochondrial membrane polarization. Also, PEG 35 preserved hepatocyte morphology as reflected by an increased F-actin/G-actin ratio and confocal microscopy findings. In addition, PEG 35 protective mechanisms were correlated with the activation of the prosurvival kinase Akt and the cytoprotective factor AMPK and the inhibition of apoptosis. Thus, PEG may become a suitable agent to attempt pharmacological preconditioning against hepatic IRI.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hui Liu ◽  
Lei Yang ◽  
Hui-Jun Wu ◽  
Kui-Hao Chen ◽  
Feng Lin ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document