Water-Soluble Nanoscale C60 Fullerenes as Effective Therapeutic Means for Prevention and Correction of Ischemic Injury in Skeletal Muscle

Author(s):  
Tetyana Yu. Matvienko ◽  
Danylo A. Zavodovskyi ◽  
Daria A. Vulytska ◽  
Svitlana Yu. Zay ◽  
Olexander P. Motuziuk ◽  
...  
1982 ◽  
Vol 60 (7) ◽  
pp. 877-884 ◽  
Author(s):  
John T. Hamilton ◽  
Peggy A. Stone

Changing trends in the use of anxiolytic agents and recent reassessment of their neuropharmacological activity has prompted this evaluation of the peripheral neuromuscular activity of the benzodiazepine, flurazepam. In previous reports we have documented peripheral neuromuscular activity of chlordiazepoxide and diazepam on the rat phrenic nerve diaphragm preparation. The water soluble benzodiazepine, flurazepam, has been studied on the rat phrenic nerve diaphragm and frog rectus abdominis in vitro. On the former preparation flurazepam enhanced and then blocked the response to indirect electrical stimulation (0.2 Hz) and readily blocked posttetanic potentiation and prevented the preparation from sustaining a tetanic contracture (30 Hz). On the later preparation, flurazepam blocked in a noncompetitive manner the response of the frog muscle to applied cholinergic agonists. Studies on the rat preparation with the neuromuscular blocking drug succinylcholine have shown an unexpected protection against blockade in preparations pretreated with low concentrations of flurazepam. This was not observed when flurazepam was given prior to d-tubocurarinc. The application of adenosine to rat diaphragms during steady-state partial blockade caused by flurazepam or d-tubocurarine showed an inhibiting action of adenosine which was reversed by theophylline. Pretreatment of rat preparations with dipyridamole significantly enhanced the blocking action of standard concentrations of succinylcholine.These results, along with those in the literature, encourage a reassessment of the action of purines and benzodiazepines on skeletal muscle and encourage a consideration of a possible involvement of purinergic neuromodulation of transmission which is unmasked when the safety factor for transmission is altered by muscle relaxants. The possible clinical significance of protection against succinylcholine by benzodiazepines is noted.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4416 ◽  
Author(s):  
Yang Hu ◽  
Qingju Li ◽  
Yunzheng Pan ◽  
Li Xu

Salvianolic acid B is one of the main water-soluble components of Salvia miltiorrhiza Bge. Many reports have shown that it has significant anti-myocardial ischemia effect. However, the underlying mechanism remains unclear. Our present study demonstrated that Sal B could alleviate myocardial ischemic injury by inhibiting the priming phase of NLRP3 inflammasome. In vivo, serum c-troponin I (cTn), lactate dehydrogenase (LDH) levels, the cardiac function and infract size were examined. We found that Sal B could notably reduce the myocardial ischemic injury caused by ligation of the left anterior descending coronary artery. In vitro, Sal B down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated H9C2 cells. Furthermore, Sal B reduced the expression levels of IL-1β and NLRP3 inflammasome in a dose-dependent manner. In short, our study provided evidence that Sal B could attenuate myocardial ischemic injury via inhibition of TLR4/NF-κB/NLRP3 signaling pathway. And in an upstream level, MD-2 may be the potential target.


Author(s):  
Louise L. Dunn ◽  
Stephanie M.Y. Kong ◽  
Sergey Tumanov ◽  
Weiyu Chen ◽  
James Cantley ◽  
...  

Objective: Hmox1 (heme oxygenase-1) is a stress-induced enzyme that catalyzes the degradation of heme to carbon monoxide, iron, and biliverdin. Induction of Hmox1 and its products protect against cardiovascular disease, including ischemic injury. Hmox1 is also a downstream target of the transcription factor HIF-1α (hypoxia-inducible factor-1α), a key regulator of the body’s response to hypoxia. However, the mechanisms by which Hmox1 confers protection against ischemia-mediated injury remain to be fully understood. Approach and Results: Hmox1 deficient ( Hmox1 –/– ) mice had impaired blood flow recovery with severe tissue necrosis and autoamputation following unilateral hindlimb ischemia. Autoamputation preceded the return of blood flow, and bone marrow transfer from littermate wild-type mice failed to prevent tissue injury and autoamputation. In wild-type mice, ischemia-induced expression of Hmox1 in skeletal muscle occurred before stabilization of HIF-1α. Moreover, HIF-1α stabilization and glucose utilization were impaired in Hmox1 –/– mice compared with wild-type mice. Experiments exposing dermal fibroblasts to hypoxia (1% O 2 ) recapitulated these key findings. Metabolomics analyses indicated a failure of Hmox1 –/– mice to adapt cellular energy reprogramming in response to ischemia. Prolyl-4-hydroxylase inhibition stabilized HIF-1α in Hmox1 –/– fibroblasts and ischemic skeletal muscle, decreased tissue necrosis and autoamputation, and restored cellular metabolism to that of wild-type mice. Mechanistic studies showed that carbon monoxide stabilized HIF-1α in Hmox1 –/– fibroblasts in response to hypoxia. Conclusions: Our findings suggest that Hmox1 acts both downstream and upstream of HIF-1α, and that stabilization of HIF-1α contributes to Hmox1’s protection against ischemic injury independent of neovascularization.


1988 ◽  
Vol 36 (7) ◽  
pp. 775-782 ◽  
Author(s):  
P Frémont ◽  
P M Charest ◽  
C Côté ◽  
P A Rogers

The objectives of the present study were to determine if carbonic anhydrase III (CA III) demonstrated a specific association for any particular organelle or structure of the skeletal muscle cell and to quantify the activity and content of this enzyme in different types of skeletal muscle fibers. Ultrastructural localization of CA III in the soleus (SOL), deep vastus lateralis (DVL), and superficial vastus lateralis (SVL), composed of predominantly type I, IIa, and IIb fibers, respectively, was performed using a high-resolution immunocytochemical technique and antibody specific for CA III on ultra-thin sections of skeletal muscle embedded in the water-soluble medium polyvinyl alcohol (PVA). The results indicated a uniform distribution of CA III within the sarcomere. Mitochondria, nuclei, triads, Z-, and M-bands were not specifically labeled. Immunoblotting of washed myofibril preparations did not show any detectable CA III associated with this structure. In addition to quantification of the immunogold labeling, CA III activity and content were assayed in the post-mitochondrial supernatant of the three muscles. In the SOL, these values were found to be 3.6-7.6 times higher than in the DVL. The SVL showed a labeling intensity slightly higher than background level, while the enzyme activity and content were indistinguishable from background levels. We therefore conclude that CA III is randomly distributed in the cytoplasm of the three muscle fiber types and that the relative CA III content and activity in the three muscles studied is SOL greater than DVL greater than SVL approximately equal to 0.


The Analyst ◽  
2016 ◽  
Vol 141 (9) ◽  
pp. 2682-2687 ◽  
Author(s):  
Angelina Cayuela ◽  
M. Laura Soriano ◽  
Miguel Valcárcel

A selective photoluminescence method based on Carbon Quantum Dots (CQDs) functionalized with carboxymethyl-β-cyclodextrin for the direct determination of water-soluble C60 fullerene has been developed.


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