Angiotensin II receptor blockade - Importance for intestinal smooth muscle tone

The significance of AT(1) and AT(2) receptor subtypes for the development of Angiotensin II (Ang II)-induced contractions of different intestinal segments was investigated. Longitudinal strips from rat jejunum, ileum, colon and rectum were prepared and treated by Ang II in a dose of 1 mu M. The specific effects on Ang II receptors were studied by pretreatment with the selective AT(1) antagonist Losartan (100 nM) or AT(2) receptor blocker PD 123319 (100 nM). The recorded force vs. time curves of smooth muscle contractions were explored by calculation of amplitudes, integral force, the power of the contraction, as well as time parameter analysis. The application of Losartan caused significant reduction of the amplitude of smooth muscle contraction of preparations from colon and rectum (2.53 +/- 0.12 g and 2.79 +/- 0.25 g, respectively) in comparison to those provoked with Ang II alone (3.43 +/- 0.38 g and 4.74 +/- 0.44 g). The blockade of AT(1) receptors completely neutralized Ang II-provoked jejunal activity. Pretreatment with PD 1233319 caused significant reduction of the amplitude of jejunal and rectal contractions (0.47 +/- 0.08 g and 2.86 +/- 0.33 g, respectively) and led to significantly higher amplitude of the ileal smooth muscle response (2.11 +/- 0.16 g). The results indicate the predominant role of AT(1) receptors for the induction of smooth muscle contraction. The blockade of AT(2) receptors affects both phases of the smooth muscle contraction - AT(2) receptors are of importance for the development of the intestinal response to Ang II, especially for the initiation and maintenance of the rectal muscle contraction.Trakia University, Stara Zagora, BulgariaTrakya University [23/2013]This work was supported by Trakia University, Stara Zagora, Bulgaria, under Grant 23/2013

Therapeutic approach of glutathione/glutathione peroxidase-4 axis modulation in the light of ferroptosis

In the 21st century beginning, the evidence of a new type of programmed cell death, different from apoptosis, began to accumulate. In 2012, the ferroptosis concept was officially introduced. It refers to a kind of cell death that is associated with iron accumulation in the cell, impaired redox potential, and ROS increment with concomitant lipid peroxidation. Ferroptosis plays an important role in the pathophysiology of several organ damages such as tumors, neurodegenerative, ischemia-reperfusion, inflammatory diseases, and others. In ferroptosis, the leading mechanism is the glutathione (GSH) depletion and inactivation of Glutathione peroxidase-4 (GPX4), which strongly shifts the oxidative balance in the cell, leading to the activation of certain signalling pathways to induce oxidative death. The article aims to focus attention on the modulation of the GSH/GPX axis as a key factor in the treatment of these diseases

Appetite–regulating hormones in rats with fructose-induced metabolic changes

Objectives: The aim of this research is to examine the effects of fructose-drinking on the plasma levels of appetite-regulating hormones insulin, leptin and ghrelin in male and female rats. Methods: Mature Wistar rats were divided as follows: two control groups - male (CM) and female (CF); two fructose-drinking groups - male (FDM) and female (FDF), received 15% fructose solution. The experiment lasted 11 weeks. At the end, insulin, leptin and ghrelin levels as well as lipid and glucose profile were assessed. Results: Plasma concentrations of the examined hormones were elevated in fructose-drinking groups. However, in the FDM group only the leptin levels were significantly increased compared to the control. In the FDF group, all three appetite-regulating hormones showed the highest concentrations in comparison to the other groups. Conclusion: Sex hormones may affect the appetite-regulation signals and could be a factor contributing to degree of metabolic changes caused by long-term fructose overconsumption

Metabolic Disorders Induced by Fructosedrinking Water Affect Angiotensin II-mediated Intestinal Contractility in Male Wistar Rats

Introduction: The high-fructose diet in rats has been reported to cause metabolic disorders such as impaired fasting glucose levels, in-sulin resistance, dyslipidemia, and dysregulation of the renin-angiotensin system. This could lead to further complications, for instance, to the smooth muscle dysfunction.Aim: The present study aimed at developing fructose-induced metabolic perturbations in rats and the investigation of their impact on angiotensin II-induced smooth muscle intestinal motility. Materials and methods: Mature Wistar rats were randomly divided into two groups (9 rats per group): control group (drinking tap water) and fructose-drinking group (15% fructose, dissolved in tap water). At the end of the experimental period (11 weeks), the plasma levels of insulin, renin, angiotensin II and creatinine, as well as the lipid profile were assessed. Morphometric analysis and lipid index calculation were also performed. The contractile properties of ileum, colon and rectum were studied using stimulation with angiotensin II in the isolated tissue bath system. Results: Our experiment showed that drinking 15% fructose solution induced dyslipidaemia accompanied by elevated lipid indexes as well as an increase in creatinine and renin plasma levels in the rats. Conclusions: Fructose drinking and consequently the developed metabolic disorders modified the Ang II-induced intestinal activity causing a gradual alteration in the distal direction with the rectum being the most strongly affected organ