scholarly journals Disorders of microcirculation in a comorbid patient

2020 ◽  
pp. 269-270
Author(s):  
L.K. Sokolova

Background. Diabetes mellitus (DM) is a global epidemic. According to the experts, by 2045 the number of patients with diabetes will rise by 48 %. Patients with diabetes are characterized by the high cardiovascular mortality and a significant reduction in life expectancy. Almost half of the deaths associated with diabetes are due to cardiovascular diseases (CVD). Patients with diabetes often have concomitant pathology (hypertension, dyslipidemia, obesity), which increases the cardiovascular risk. Objective. To describe microcirculation disorders in patients with comorbid conditions. Materials and methods. Analysis of literature sources on this topic. Results and discussion. Type 2 diabetes (DM2) is a multifaceted disease that has a number of cardiovascular, metabolic and renal complications. The links of the pathogenesis of cardiovascular complications of DM2 include dyslipidemia, systemic inflammation, insulin resistance, autonomic imbalance, and endothelial dysfunction (ED). ED leads to vasoconstriction, increased chronic inflammation, increased vascular permeability and hypercoagulation, which ultimately causes micro- and macroangiopathy. Neurological complications of diabetes are also mediated by ED and microangiopathies, which lead to nerve hypoxia with a decrease in conductivity velocity. In recent years, the literature has been actively discussing the syndrome of early vascular aging – premature and accelerated development of structural and functional age-related changes in blood vessels. Microcirculation disorders that accompany diabetes, CVD and their complications are mediated by nitric oxide (NO) imbalance. NO reduces the contractility and proliferation of smooth muscle cells, platelet aggregation, endothelin production, adhesion of monocytes and platelets, and oxidation of low-density lipoproteins. In humans, NO is produced from L-arginine. Increased L-arginase activity and decreased NO-synthase activity lead to a decrease in NO content and to the development of ED, atherosclerosis, and decreased insulin sensitivity. L-arginine as a substrate of NO improves the functional state of the endothelium, reduces the manifestations of oxidative stress, reduces the level of pro-inflammatory cytokines and adhesion molecules, inhibits platelet aggregation, reduces insulin resistance. It should be noted that the administration of 4.2 g of L-arginine in DM is not enough. In clinical studies, doses of 6.4-9 g per day were found to be effective in diabetes and obesity. Therefore, it is advisable to use Tivortin-200 (“Yuria-Pharm”), which contains 8.4 g of L-arginine in one vial. Conclusions. 1. Patients with diabetes are characterized by the high cardiovascular mortality and a significant reduction in life expectancy. 2. The links of the pathogenesis of cardiovascular complications of DM2 include dyslipidemia, systemic inflammation, insulin resistance, autonomic imbalance, and ED. 3. Disorders of microcirculation that accompany diabetes, CVD and their complications, are mediated by NO imbalance. 4. L-arginine as a substrate of NO improves the functional state of the endothelium, reduces the manifestations of oxidative stress, reduces the level of pro-inflammatory cytokines and adhesion molecules, inhibits platelet aggregation, reduces insulin resistance. 5. In diabetes and obesity, it is advisable to use Tivortin-200, which contains 8.4 g of L-arginine in one vial.

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.


Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.


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