scholarly journals Changes of L-Arginine Metabolism in Rat`S Colon Mucosa Under the Conditions of COX/LOX Inhibition and Acute Stress Action

2021 ◽  
Vol 18 (2) ◽  
pp. 313-326
Author(s):  
Nataliya Denysenko ◽  
Alexander Sklyarov

Introduction. L-arginine is a semi-essential amino acid and a precursor of many biologically active compounds. Polyamines and NO produced from L-arginine take part in the regulation of biochemical processes in colon mucosa. Emotional stress, nonsteroidal anti-inflammatory drugs (NSAIDs) and their combined action can change the activity of L-arginine metabolizing enzymes. The aim of this study was to investigate the single action of NSAIDs with different mechanisms of action and their combination with acute stress on L-arginine metabolism in colon mucosa of rats. Methods. Animals were divided into 8 groups: control group (1), administration of nonselective, COX-2 selective and dual COX-2/5-LOX inhibitors (groups 2-4), acute stress group (5), administration of same NSAIDs as in groups 2-4 under the conditions of acute stress (groups 6-8). The activity of iNOS, cNOS, arginase, concentration of L-arginine, nitrite and nitrate was measured in colon mucosa. Results. Nonselective COX inhibition by naproxen caused the increase in iNOS and decrease in cNOS activity in colon mucosa. Both COX-2 (celecoxib) and dual COX-2/5-LOX (2A5DHT) inhibitors enhanced cNOS and arginase acting in combination with acute stress. The concentration of L-arginine remained unchanged in most of the groups, but combination of dual COX-2/5-LOX inhibitor and acute stress raised this parameter.

Author(s):  
N. V. Denysenko ◽  
O. Ya. Sklyarov

Introduction. Extensive, and often uncontrolled, use of cyclooxygenase (COX) inhibitors, as well as the psychological stress, are important factors of inflammatory diseases development in the digestive tract, including the large intestine. The activation of lipoperoxidation processes is one of the pathogenetic links of the development of ulcers, which can serve as a marker for both the intensity of inflammation and the onset of proinflammatory state. The aim of the study – to find out the influence of certain COX and lipoxygenase (LOX) inhibitors on the activi­ty of free radical oxidation and the morphological state of the colon mucosa (CM) under the conditions of their independent action and under the conditions of stress. Research Methods. A model of 5 hours water-immobilization stress was selected for the stress simulation, for inhibition of COX and LOX – naproxen, celecoxib and compound 2A5DHT, which were administered intragastrically, in a single dose of 10 mg/kg. The morphological study of CM and the determination of the antioxidant enzymes activity in the CM homogenates were conducted. Results and Discussion. The single action of naproxen caused increase of SOD, catalase, MPO activity and TBA-active products concentration in the CM. Similar changes were noted under the conditions of stress. Administration of naproxen under the conditions of stress caused the increase of SOD activity compared to WIS action and increase of TBA-active products concentration, activity of catalase and MPO compared to naproxen action. Conclusions. It was found that non-selective COX inhibition was accompanied by proinflammatory effect in the CM, likely based on the prooxidant action of the nonselective COX inhibitor, which was confirmed by the activation of SOD. Selective COX-2 inhibition and inhibition of COX-2/5-LOX showed an anti-inflammatory effect due to a more effective mechanism of action.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Radwa Nasser Muhammad ◽  
Nada Sallam ◽  
Hanan Salah El-Abhar

Abstract 5-Fluorouracil (5-FU) is used in the treatment of different solid tumors; however, its use is associated with rare, but serious cardiotoxicity. Nevertheless, the involvement of ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 trajectories in the cardiotoxic effect and in the potential cardioprotective upshot of simvastatin has been elusive. Male Wistar rats were allocated into 5-FU (50 mg/kg/week; i.p, 6 weeks), simvastatin (15 mg/kg/day; p.o, 8 weeks) treated groups and simvastatin + 5-FU, besides the normal control group. 5-FU-induced cardiotoxicity boosted the serum level of N-terminal pro-brain (B-type) natriuretic peptide (NT-proBNP), aortic contents of endothelin (ET)-1 and thromboxane (TX) A2, as well as cardiac contents of NADPH oxidases (Nox), cyclooxygenase (COX)-2, malondialdehyde (MDA), phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and the protein expressions of rho-kinase (ROCK) and caspase-3. On the other hand, it suppressed cardiac reduced glutathione (GSH) and phosphorylated endothelial nitric oxide synthase (p-eNOS). Contrariwise, co-administration with simvastatin overcame these disturbed events and modulated the ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 signaling pathways. This study highlights other mechanisms than coronary artery spasm in the 5-FU cardiotoxicity and reveals that NT-proBNP is a potential early marker in this case. Moreover, the cross-talk between ROCK/ NF-κB, ROS/COX-2/TXA2, Akt/eNOS and ET-1/ERK1/2 pathways contributes via different means to upsetting the vasoconstriction/vasodilatation equilibrium as well as endothelial cell function and finally leads to cardiomyocyte stress and death—the modulation of these trajectories offers simvastatin its potential cardio-protection against 5-FU.


2017 ◽  
Vol 87 (3-4) ◽  
pp. 179-190
Author(s):  
Amel Kanane ◽  
Fayrouz Rouaki ◽  
Mohamed Brahim Errahmani ◽  
Abdenour Laraba ◽  
Hayet Mesbah ◽  
...  

Abstract. The aim of this study is to evaluate the effect of α-tocopherol supplementation at two doses (600 and 1200 mg × kg–1) on kidney antioxidant status and the histopathological changes in Wistar rats after 12 weeks of exposure at different diets. Forty rats has been divided into 4 groups of 10 rats each, the control group received basal diet with 5 % fresh sunflower oil (FSO), the second group: 5 % oxidized sunflower oil (OSO), the third group: 5 % OSO supplemented with 600 mg × kg–1 α-tocopherol and the fourth group: 5 % OSO supplemented with 1200 mg × kg–1 α-tocopherol. In OSO groups, the results showed highly significant increases of LPO (from 31.3 ± 0.9 to 53.8 ± 1.2 nmol of MDA formed/min/mg protein, p < 0.0001) with a significant decrease (p < = 0.001) of the antioxidant enzymatic activities (CAT, SOD, GPX, GR and G6PDH), body weight (339 ± 9 to 290 ± 3 g) and α-tocopherol levels (13.6 ± 0.6 to 6.5 ± 0.4 μg/mg protein). In OSO groups with 600 mg × kg–1 α-tocopherol, an antioxidant effect was found, reflected by a return of the parameters to values similar to those of the control group. However, higher doses of α-tocopherol (1200 mg × kg–1) induced a depletion of antioxidant status, α-tocopherol levels (6.0 ± 0.3 μg/mg protein, p < 0.001) and a very highly significant rise (p < 0.0001) of LPO content (54.86 ± 0.01 nmol of MDA formed/min/mg protein). The kidney tissues also showed changes in glomerular, severe inflammatory cells infiltration, and formation of novel vessels. So, we can conclude that the oxidative stress is attenuated by a moderate administration of 600 mg × kg–1 α-tocopherol, while a pro-oxidant effect occurs at 1200 mg × kg–1 α-tocopherol.


Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.


Author(s):  
N. N. Malyutina ◽  
A. F. Bolotova ◽  
R. B. Eremeev ◽  
A. Zh. Gilmanov ◽  
D. Yu. Sosnin

Introduction. The overwhelming number of publications contains only data on the content of individual antioxidants, but not on the overall antioxidant activity of the blood in patients with vibration disease.The aim of the study was to determine the total antioxidant activity of blood serum in patients with vibration disease.Materials and methods. Th e main group consisted of 30 people diagnosed with “Vibration disease” of 1 degree (n=21) and 2 degrees (n=9). Th e control group consisted of 30 clinically healthy men, comparable in age with the main group (p=0.66). Th e total activity of antioxidant systems of blood plasma was evaluated photometrically using the test system “Total antioxidant status-Novo” (“Vector-best”, Russia).Results. The indicator of the total antioxidant status (TAS) was 1,038±0.232 mmol/l in the examined main group, against 1,456±0.225 mmol/l in the examined control group (p<0.000001). Th e coefficient of variation (CV) in patients with vibration disease was 22.35%, 1.45 times higher than in the control group (15.45%). In the main group there was a positive correlation between age and TAS (R=0.525), in the control group there was no such relationship (R=0.095). Th e degree of decrease depended on the severity of vibration disease.Conclusions. 1. The development of vibration disease is accompanied by a decrease in the antioxidant status of blood serum. 2. Th e degree of decrease in the antioxidant status of blood serum correlates with the severity of vibration disease. 3. Reduction of TAS can serve as a pathogenetic justification of the need to include drugs and/or biologically active additives with antioxidant activity in therapy


Author(s):  
A. Farkhutdinova

The expediency of using the probiotic drug Biolax-U in the rations of lactating and dry cows of Black-and-White breed has been studied and scientifically proved. The influence of this drug on the morphological and biochemical parameters of animal blood has been determined. The composition of the probiotic drug Biolax-U consists of eight strains of a balanced complex of living lactic acid bacteria, yeast and actinomycetes, as well as biologically active substances. For experimental studies conducted on 2 groups of cows have been selected by the method of pairs-analogs, the influence of feeding of feed have been prepared with the use of the microbiological drug with probiotic action Biolax-U on feed consumption, morphological and biochemical changes in blood has been studied. Analysis of the rations of cows indicates that the content of calcium, phosphorus, magnesium, sulfur and trace elements such as manganese, copper, zinc and cobalt in the feed has been reduced. It has been found by studies that the use of probiotic drug Biolax-U had the positive influence on the feed intake, digestibility and better assimilation of feed nutrients and contributed to the improvement of blood morphological and biochemical parameters. For example, in animals of the experimental group hemoglobin has increased by 3,6 % (Р < 0,05), red blood cells by 10,1 (P ≤ 0,05), the content of leukocytes by 4,43, carotene by 9,6, glucose by 3,4; reserve alkalinity by 15,6, calcium by 19,4 (P ≤ 0,01), and phosphorus by 18,4 % compared with the control group of animals. During the lactation significantly improved hematological parameters including alkalinity reserve by 5,11 %, calcium level by 11,1, phosphorus by 8,6, hemoglobin by 14,2 %, the content of erythrocytes by 12,3, leukocyte by 3,86, and carotene 11,1 % against the parameters of animals of control group. The improvement of morphological and biochemical parameters of blood of cows indicates about stimulating effect on hematopoiesis and the general clinical condition of animals that contributes to the improvement of metabolic processes when using feed prepared with the use of microbiological drug with probiotic action Biolax-U.


2018 ◽  
Author(s):  
Franziska Lautenbach

BACKGROUND Dealing with stress is of central importance. Lately, smartphone applications (apps) are deployed in stress interventions as they offer maximal flexibility for users. First results of experimental studies show that anti-stress apps effect subjective perception of stress positively (Ly et al., 2014). However, current literature lacks studies on physiological stress reactions (e.g., cortisol), although they are of special interest to health issues. OBJECTIVE Therefore, the aim of this study was to investigate the effectiveness of an anti-stress app in chronic and acute stress reduction on a physiological (cortisol) and psychological level (subjective perception of stress) in comparison to a face-to-face and a control group in a pre-post design, for the first time. METHODS Sixty-two participants took part in the pretesting procedure (drop-out of 53 %). Based on age, gender, physical activity and subjectively perceived acute stress due to the Trier Social Stress Test for groups (TSST-G; von Dawans et al., 2011) as well as based on subjectively chronic stress assessed during the pretest, participants were parallelized in three groups (anti-stress-app: n = 10, face-to-face: n = 11, control group: n = 9). RESULTS After six weeks of the cognitive-based resource-oriented intervention, participants were exposed to the TSST-G for post testing. Results did not show a change of cortisol secretion or cognitive appraisal of the acute stressor. Further, no changes were detected in the chronic physiological stress reaction. CONCLUSIONS Possible causes are discussed extensively. CLINICALTRIAL no


BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Fariba Heshmati Afshar ◽  
Masumeh Zadehkamand ◽  
Zahra Rezaei ◽  
Abbas Delazar ◽  
Vahideh Tarhriz ◽  
...  

Abstract Background Artemisia splendens from the Asteraceae family is a new source of biologically active compounds. The current study investigated to evaluate antimicrobial and cytotoxicity activity of methanolic extracts and their fractions obtained from aerial parts by agar disk diffusion and MTT methods, respectively. The active fractions were subjected to preparative HPLC for isolating the pure compounds, which were structurally elucidated, by 1H and 13C NMR. Results The results showed that the methanolic extract and its 60% SPE fraction have the anti-proliferative activity on A549 cell line in comparison with the control group. Meanwhile, the methanolic extract and its 40% SPE fraction can inhibit the growth of Gram-positive strains as anti-microbial activity. The 60% SPE fraction also illustrated anti-proliferative activity on the HT-29 cell line compared to the control group. Chromatographic separations via preparative HPLC yielded 5 flavonoids and three flavonoid glycosides. Conclusion Based on the results it can be concluded that A. splendens as a potential source of cytotoxic and antimicrobial compounds can be used in pharmaceutics.


1974 ◽  
Vol 76 (3) ◽  
pp. 556-569 ◽  
Author(s):  
E. Nieschlag ◽  
K. H. Usadel ◽  
H. K. Kley ◽  
U. Schwedes ◽  
K. Schöffling ◽  
...  

ABSTRACT A new method for the investigation of hypothalamo-pituitary-gonadal and adrenal feedback control mechanisms based on the biological neutralization of gonadal and adrenal steroids by active immunization is proposed. The regulatory influence of a given steroid in the feedback control is proved when reduction of the free, biologically active fraction of this steroid caused by antibody binding induces a positive response of the pituitary, thus effecting gonadal or adrenal hypertrophy and hyperfunction. The advantages and limitations of the new model are demonstrated by the effects of active immunization of rabbits with cortisol (F), aldosterone (Aldo), dehydroepiandrosterone (DHA), androstenedione (Δ4-A), testosterone (T), 5α-dihydrotestosterone (5α-DHT), 5β-DHT and oestradiol (E2). In the immunized animals and in a control group serum concentrations of total corticosteroids (TC), DHA, T, Δ4-A, E1, E2, LH and FSH, the percentage of binding of steroids in serum and the specificity of the antisera are determined. The testes are evaluated by histometry and the nuclear volume of the adrenocortical and Leydig cells is measured.


2021 ◽  
Vol 11 (4) ◽  
pp. 508
Author(s):  
Michael Schaefer ◽  
Julian Hellmann-Regen ◽  
Sören Enge

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.


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