Activity Of Enzyme System Research Articles

Synthesis and Antioxidative Activity of Piperine Derivatives Containing Phenolic Hydroxyl

Piperine was used in this study in its raw form, and different steps, such as amide hydrolysis and amidation, were used to synthesize piperine derivatives containing a phenolic hydroxyl group. DPPH and ABTS free radical scavenging assays were used to assess piperine derivative antioxidant activities. We constructed an AAPH oxidative stress erythrocyte model to study the effect of piperine derivatives on the hemolysis rate of oxidatively damaged erythrocytes as well as the hemoglobin oxidation rate. This AAPH model was also used to determine piperine derivative effects on antioxidant enzyme activity and malondialdehyde (MDA) content. Results showed that spectroscopic methods could synthesize and identify piperine derivatives containing phenolic hydroxyl groups (H-1∼H-3). Moreover, DPPH and ABTS assay results showed that piperine derivative free radical clearance rates were higher compared with the parent compound. Additionally, piperine derivatives (H-1∼H-3) were found to provide protection to AAPH oxidatively damaged erythrocytes in their ability to inhibit AAPH-induced erythrocyte lysis, while hemoglobin oxidation was higher compared with the parent compound. Piperine derivatives may protect intracellular glutathione peroxidase (GSH-Px) antioxidant enzyme system activities, safeguarding against oxidative damage. This study synthesized novel piperine derivatives for use as potential antioxidant agent candidates.

Effect of sodium selenite and feed additive “Metisevit plus” on morphological parameters of blood of rats at the intoxication of Cadmium and Lead

Heavy metals, Lead and Cadmium, are hazardous environmental pollutants. In the body of mammals, Cadmium and Lead have a toxic effect on a number of organs and systems. The mechanism of action of these poisons is to inhibit the activity of enzyme systems by blocking carboxyl, amine and SH groups of protein molecules. The aim of the study was to investigate the effect of sodium selenite and feed additive “Metisevit plus” on the morphological parameters of rat blood by Cadmium and Lead intoxication. The experiments were carried out on 200–220 g male Wistar rats, out of which 3 groups of animals were formed: a control and two experimental animals. Rats in the control and experimental groups were administered 16.6 % aqueous lead acetate at a dose of 100 mg/kg and 0.029 % aqueous cadmium chloride at a dose of 2.0 mg/kg. The rats of the first experimental group additionally used sodium selenite. The rats of the second experimental group additionally used the feed additive “Metisevit plus”. Lead-cadmium loading in rats was accompanied by erythrocytopenia and leukopenia. The lowest erythrocyte count was in the blood of diseased rats at 21 days, where it decreased by 41.3 %, respectively, compared to the initial values. It was found that hemoglobin level decreased to 90.3 ± 2.63 g/l during Cadmium and Lead intoxication in control rats. At the same time as the decrease in hemoglobin level and the number of erythrocytes in intoxicated rats, an increase in the average hemoglobin content in one erythrocyte of blood was observed up to 20.57 ± 1.20 pg As a result of the development of lead-cadmium intoxication in ill rats, leukopenia was noted, which, in our opinion, is associated with systemic lesions of cadmium and lead in the blood-forming organs of animals that suppress leukopoiesis. It was found that the number of leukocytes in patients of rats of group C decreased by 36.1 % compared with the initial data. The use of sodium selenite and the feed additive “Metisevit plus” in rats under lead-cadmium loading contributed to the increase in the number of red blood cells and hemoglobin level, as well as the decrease in the number of leukocytes in their blood. The improvement of normalizing effect on the morphological parameters of blood of rats under conditions of loading with heavy metals was shown by the feed additive “Metisevit plus” in comparison with sodium selenite.

The activity of the antioxidant protection enzymatic system of boars with a decrease in their reproductive capacity under oxidative stress

It was found that enzymatic system activity of the antioxidant protection of the breeding boars organism with a decrease in their reproductive ability under oxidative stress was significantly decreased, which was noted by a decrease in the antioxidant capacity. Males of the experimental group had a decrease in superoxide dismutase activity by 30,2% (p ˂ 0,01). At the same time, in the erythrocytes of breeding boars, catalase activity was reduced by 33,9% (p ˂ 0,001) compared with the indicators of the control group animals, due to the high sensitivity to nitric oxide, the content of which was significantly increased during oxidative stress; interacting with nitric oxide, a suppressed form of catalase – ferricatalase-NO was formed. A decrease in the activity of these enzymes is characteristic of the oxidative stress development – which is due to the high level of peroxidation processes in the body of breeding boars. With a decrease in the activity of glutathione system components, an imbalance of the prooxidant-antioxidant system was noted. According to the research results, a decrease in the activity of the glutathione redox cycle enzymes – glutathione peroxidase and glutathione reductase was noted, which in boars with a decrease of reproductive ability were also reduced, and this also confirmed the state of oxidative stress. Thus, boars of the experimental group had a pronounced decrease in glutathione peroxidase activity by 28,4% (p ˂ 0,05), while the activity of glutathione reductase in erythrocytes was significantly reduced by 20,2% (p ˂ 0,05). The lack of physiological activity of antioxidant enzymes will have a negative impact on the fertilizing ability of sperm, because the lack of components of the enzymatic antioxidant defence system affects the activity of enzymes in sperm received from the breeding boars. A balance was observed between the components of the enzymatic antioxidant defense: the ratio of antioxidant enzymes’ activity in the male experimental group was lower than the values in the control group, however, the indices of superoxide dismutase/catalase and glutathione peroxidase/glutathione reductase had the same values, indicating that the balance in the enzymatic system of antioxidant defense was maintained. A decrease in enzyme indices in the experimental group indicated a decrease in the antioxidant potential and confirmed a certain state of oxidative stress in the breeding boars organism.

BIOSYNTHESIS OF PROTEINASES AND PECTINASES BY WINE YEASTS

The relevance of research is determined by the need to use the biological potential of wine yeast to improve the quality of wines and ensure their stability against colloidal turbidity. The purpose of the research is to determine the activity of enzyme systems, proteinases,and pectinases, synthesized by wine yeast during alcohol fermentation and autolysis, depending on their race and the duration of contact of the wine material with yeast biomass. To determine the enzyme activity, yeasts of different strains were incubated on media containing the following substrates: albumin for proteinases, apple pectin for pectinases. The biosynthesis of proteinases and pectinases by various races of wine yeast was studied as well as their secretion into wine material. The research has shown that the activity of proteinases in the cell biomass and wine materials varies widely depending on the race of the yeast, which is explained by their genetic characteristics. The absence of a correlation between the activity of proteinases in yeast biomass and wine material has been established. For the first time, it has been shown that the biomass of active dry yeast cells has a large supply of proteinases in comparison with the yeast starters of races produced in Russia. The activity of pectinases in yeast biomass is significantly less than the activity of proteinases, which is due to a lower concentration of the substrate - pectin substances. The paper suggests several interpretations of the mechanisms of biochemical processes occurring during the contact of yeast biomass and wine materials. The paper contains experimental data on the effect of proteinases and pectinases synthesized by wine yeast on the composition of wine biopolymers. The study identifies the yeast strains that actively hydrolyze the high-molecular components of wine and complexes of biopolymers, and prolong the resistance of wines to colloidal turbidity.

ADJUSTING FLOUR QUALITY BY ENZYMES: CURRENT STATE, PROBLEM ANALYSIS, FUTURE DEVELOPMENT PROSPECTS

The article overviews the issue of wheat flour modification by enzymes. The role of enzymes in the dough formation process is considered. Modern ways of providing the desired dough parameters for flour products in conditions of Ukraine are shown. Recommendations and suggested directions for further research are given. Flour is a complex multicomponent product and have to correspond with a number of requirements for its composition and properties. Different conditions of grain cultivation and storage result in significant deviations of its quality indicators when it comes to flour mills. The modification of flour going through adding several technological additives, in particular by enzyme products. The action of enzymes to a large extent allows to adjust the properties of the dough and of flour end-products. In addition, enzymes further affect the nutritional values of flour, which makes it possible for the flour production to use low-quality grain, while maintaining the planned quality indicators of flour. The functional properties of flour fractions obtained on different technological passages depend on the content of various anatomical parts of the grain from which they derived from. Particle size, starch damage, protein content, fat content, ash content and intensity of enzyme activity vary significantly depending on the type of grinding equipment. All this gives reason for recommending the introduction of enzymes not while manufacturing bakery end-products but still at the stage of flour production. The damage to the grain with a corn bug, grain germination in Ukraine puts grain-processing plants the task of assessing the activity of own grain enzyme systems. Indirectly, this can be estimated using the gluten deformation index and the grain Falling Number. But the estimation of enzyme systems by such methods does not allow precisely to calculate the amount and composition of enzyme products necessary to achieve maximum effect when adjusting flour properties. The issue of removing anti-nutrient factors in flour, which is largely inhibitors of the action of both their own grain enzyme systems and additionally introduced enzyme preparations, is also relevant.

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes.

Flavonoids have been demonstrated to affect the activity of many mammalian enzyme systems. Their functional phenolic groups are able to mediate antioxidant effects by scavenging free radicals. Molecules of this class have been found able to modulate the activity of kinases, phospholipase A2, cyclooxygenases, lipoxygenase, glutathione S-transferase, and many others. Recently, it has been demonstrated that luteolin, in the form of Luteolin-7-O-β-d-glucoside (LUT-7G) is able to induce the keratinocyte differentiation process in vitro. This flavonoid is able to counteract the proliferative effects of IL-22/IL6 pathway by the inhibition of STAT3 activity also in vivo in a psoriatic mouse model. Observations on energy metabolism changes of differentiating cells led us to perform a complete metabolomics analysis using human primary keratinocytes treated with LUT-7G. Our results show that LUT-7G, is not only able to impair the nuclear translocation of STAT3, but it also blocks the energy metabolism pathway, depressing the glycolytic and Krebs pathway by the inhibition of hexokinase 2 activity. These data confirm that LUT-7G can be proposed as a potential candidate for the treatment of inflammatory and proliferative diseases, but its role as a hexokinase 2 (HEK2) inhibitor opens new perspectives in nutritional science, and especially in cancer therapy, in which the inhibition of the Warburg effect could be relevant.

Red Quinoa Bran Extracts Protects against Carbon Tetrachloride-Induced Liver Injury and Fibrosis in Mice via Activation of Antioxidative Enzyme Systems and Blocking TGF-β1 Pathway.

The late stages of liver fibrosis are considered to be irreversible. Red quinoa (Chenopodium formosanum Koidz), a traditional food for Taiwanese aborigines, was gradually developed as a novel supplemental food due to high dietary fibre and polyphenolic compounds. Its bran was usually regarded as the agricultural waste, but it contained a high concentration of rutin known as an antioxidant and anti-inflammatory agent. This study is to explore the effect of red quinoa bran extracts on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis. BALB/c mice were intraperitoneally injected CCl4 to induce liver fibrosis and treated with red quinoa whole seed powder, bran ethanol extracts, bran water extracts, and rutin. In the results, red quinoa powder provided more protection than rutin against CCl4-induced oxidative stress, pro-inflammatory factor expression and fibrosis development. However, the bran ethanol extract with high rutin content provided the most liver protection and anti-fibrosis effect via blocking the tumor necrosis factor alpha (TNF-α)/interleukin 6 (IL-6) pathway and transforming growth factor beta 1 (TGF-β1) pathway.

Differential toxicity of anatase and rutile TiO2nanoparticles to the antioxidant enzyme system and metabolic activities of freshwater biofilms based on microelectrodes and fluorescencein situhybridization

A first attempt to compare the eco-toxicities of An-NPs and Ru-NPs to freshwater biofilms in terms of the spatiotemporal microenvironment.

Biochemical and morphological changes in muscular tissue of pond fish in the process of autolytic transformations

Physical and chemical processes in muscular tissue of pond fish are considered in the process of storage. The muscle contraction appears mainly because of the myofibrils activity that utilizes energy of the sarcoplasm substances. Intense disintegration of glycogen causes sharp acidification (pH decreasing) in the muscular tissue that affects on chemical composition and physical-colloidal structure of proteins. Hardening of the muscular tissue is observed in the first hours of storage because of the proteins transformation to actin and myosin in insoluble actomyosin complex. The highest level of actomyosin is observed in the first 3–5 hours that is the evidence of unstable rate of biochemical processes corresponded to changing activity of enzyme systems. Cumulative level of the actomyosin complex grows in the first 8 hours of storage for all investigated fish species. Organoleptic and technological characteristics of the fish meat improve significantly in the process of its maturation: the meat has no definite taste and smell in early stages of autolysis, but these properties appear in 3–4 days, depending on the storage temperature, due to enzymatic decomposition of proteins, peptides, nucleotides, carbohydrates, lipids, etc. Recommendations on storage are presented for certain groups of fish products in dependence on initial properties of raw materials.

Екологічна оцінка питної води Лугинського району Житомирської області на вміст хлоридів, сульфатів та нітратів

Здійснено екологічну оцінку стану води водогонів та колодязів Лугинського району Житомирської області на вміст хлоридів, сульфатів та нітратів. Здійснено моніторинг ситуації в тих населених пунктах, де є і водогін, і колодязі. Сюди належать смт Лугини, села Великий Дивлин, Липники, Червона Волока, Миролюбів (стара назва Жовтневе). Проведено низку досліджень за 2014, 2015, 2016 рр. У динаміці досліджуваних років встановлено тенденцію до збільшення вмісту забруднювачів групи кислотних залишків як у джерелах централізованого, так і децентралізованого водопостачання. Другою встановленою закономірністю виявився збільшений вміст усіх досліджуваних забруднювачів у колодязях порівняно з водогонами. Однак, якщо для хлоридів та сульфатів перевищень норм ДСанПІН 2.2.4-171-10 не виявлено, то вміст нітратів у деяких досліджуваних зразках був вищим за норму впродовж усіх досліджуваних років. Пояснити ситуацію можна зменшенням водності річок протягом останніх років та пониженням рівня підґрунтових вод, що призводить до збільшення концентрації усіх забруднювальних речовин, зокрема і нітратів. Особливо критичною ситуація була влітку 2016 р. У криницях деяких господарів води не було взагалі. Отже, не можна стверджувати, що ситуація з питним водопостачанням Лугинського району Житомирської області є безпечною. У посушливі роки, а саме такими були досліджувані, стаються спалахи забруднення питної води нітратами.

Di (2-ethylhexyl) phthalate (DEHP)-induced hepatotoxicity in quails (Coturnix japonica) via triggering nuclear xenobiotic receptors and modulating cytochrome P450 systems

Di (2-ethylhexyl) phthalate (DEHP) is a widely distributed pollutant that is of great concern due to its negative health effects. However, whether DEHP exposure causes liver toxicity in birds remains unclear. To clarify the potential hepatotoxicity of DEHP, quails were exposed to 0, 250, 500 and 1000 mg/kg BW/day DEHP by gavage treatment for 45 days. The livers of DEHP-exposed quails showed histomorphological changes. DEHP exposure induced a significant increase in cytochrome P450 enzyme system (CYP450s) activity (including aniline-4-hydroxylase (AH), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND) and NADPH-cytochrome C reductase (NCR)) and in the contents of total cytochrome P450 (CYP450) and cytochrome b5 (Cyt b5) in quail liver. DEHP exposure also influenced the expression of nuclear xenobiotic receptors (NXRs) and CYP450 isoforms in the liver. The results suggested that DEHP-induced hepatotoxicity in quail liver is associated with activation of the NXRs pathway responses and disruption of CYP450s homeostasis. This study will help to further elucidate DEHP exposure-induced liver toxicity in quails.

Effect of La3+ on seed germination and seedling growth of Salvia miltiorrhiza

The purpose of this study is to determine the effect of La3+ solution on seed germination and seedling growth of Salvia miltiorrhiza. Different concentrations of La3+ were used on seed by soaking treated to determine which concentration is the most suitable for the growth of S. miltiorrhiza. Results show that the low concentration of La3+ displays the promotion effect on S. miltiorrhiza seed germination rate and germination potential, and the promotion effect reaches the highest level when the concentration of La3+ solution is 30 mg/L, the germination index and vigor index are the highest in 20 mg/L, and it can also increase the contents of soluble sugar, soluble protein and chlorophyll. Meanwhile, the activity of antioxidant enzyme system (CAT and SOD) are improved, thus the photosynthesis and resistance of plant are enhanced. On the contrary, when the La3+ concentration is high, La3+ can inhibit plant growth. Thus La3+ displays the "homesis effect" on S. miltiorrhiza growth.

Atrazine-xenobiotic nuclear receptor interactions induce cardiac inflammation and endoplasmic reticulum stress in quail (Coturnix coturnix coturnix)

Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail. ATR exposure increased the Cytochrome P450s and Cytochrome b5 contents, Cytochrome P450 (CYP) enzyme system (APND, ERND, AH, and NCR) activities and the expression of CYP isoforms (CYP1B1, CYP2C18, CYP2D6, CYP3A4, CYP3A7, and CYP4B1) in quail heart. The expression of nuclear xenobiotic receptors (NXRs) was also influenced in the heart by ATR exposure. ATR exposure significantly caused the up-regulation of pro-inflammatory cytokines (TNF-α, IL-6, NF-κB, and IL-8), down-regulation of anti-inflammatory cytokines (IL-10) expression levels and increased NO content and iNOS activity. The present research provides new insights into the mechanism that ATR-induced cardiotoxicity through up-regulating the expression levels of GRP78 and XBP-1s, triggering ER stress, activating the expression of IRE1α/TRAF2/NF-κB signaling pathway related factors (IRE1α, TRAF2, IKK, and NF-κB) and inducing an inflammatory response in quail hearts. In conclusion, ATR exposure could induce cardiac inflammatory injury via activating NXRs responses, disrupting CYP homeostasis and CYP isoforms transcription, altering NO metabolism and triggering ER stress and inflammatory response by activating IRE1α/TRAF2/NF-κB signaling pathway.

ANTIOXIDANT DEFENSES OF IRRIGATED FORAGE SORGHUM WITH SALINE AQUACULTURE EFFLUENT

ABSTRACT The objective of this work was to evaluate the biomass production and antioxidant enzymatic system activity of irrigated forage sorghum with saline aquaculture effluent under different leaching fractions. The experiment was conducted in the Caatinga Experimental Field of the Embrapa Semiarido, in Petrolina, State of Pernambuco, Brazil. The experimental design was a complete randomized block in a split-plot arrangement with four replications, consisting of three forage sorghum varieties (Volumax, F305 and Sudan) and four leaching fractions (0, 5, 10 and 15%). The vegetal materials were collected when the plants were at the soft-dough stage. The biomass production and activity of the enzymes superoxide dismutase, catalase and ascorbate peroxidase were evaluated. Irrigation with saline aquaculture effluent with leaching fraction of 15% results in low salinity level in the root zone and higher biomass production of forage sorghum Sudan and F305, in semiarid conditions. The antioxidant system was activated in the three sorghum varieties to prevent accumulation of reactive oxygen species, with the synchrony between the enzymes superoxide dismutase and catalase resulting in a better productive response of the varieties Sudan and F305.

Study of the neuroprotective effects of carnosine in an experimental model of focal cerebral ischemia/reperfusion

Oxidative stress is one of the key factors in brain tissue damage in ischemia, which indicates the appropriateness of using antioxidants under these conditions. One of the promising antioxidants for the therapy of ischemic stroke is the natural dipeptide carnosine. The neuroprotective effect of dietary carnosine administration was investigated in an experimental model of focal cerebral ischemia/reperfusion in Wistar rats. Animals received carnosine with a diet at a daily dose of 150 mg/kg for 7 days before temporary occlusion of the middle cerebral artery (MCA), performed for 60 min. At 24 h after the onset of ischemia the effect of carnosine on the area of the necrotic core was evaluated in animals. In brain tissue of animals the content of malondialdehyde (MDA), protein carbonyls (PC), total antioxidant capacity (TAC), total activity of superoxide dismutase (SOD), glutathione peroxidase (GP), catalase (CAT) and glutathione transferase (GT), content of isoprostanes and cytokines were measured. Carnosine significantly reduced the infarct size. Carnosine also increased TAC and reduced the level of MDA and isoprostanes in brain tissue. Influence of carnosine on other parameters was not detected. Thus carnosine consumed prophylactically with the diet for 7 days before the induction of ischemia by means of MCA occlusion in rats provides the direct neuroprotective effect, retains high antioxidant activity of brain tissue, reduces the level of oxidative damage markers (MDA and isoprostanes) but does not have any effect on the activity of antioxidant enzyme systems and production of cytokines in brain tissue.

Effects of Aluminum Stress on Protective Enzyme Activity in Tie Guanyin leaves

The experiment was adopted to study the change of SOD, CAT and POD activity of Tie guanyin (new leaf and old leaf blade of different concentrations of aluminum stress; in this paper, 0 (CK), 40, 200, four gradients of 400mg/L concentration of Al3+ in acidic conditions, Tieguanyin tea leaf SOD, cat and POD activity changes. The results showed that high concentrations of aluminum stress on antioxidant enzyme system activity cannot continue to increase; at the same time showed that SOD is sensitive to aluminum toxicity concentration change, its sensitivity is higher than CAT and POD, SOD and CAT activity and the aging and decline of plant There was a positive correlation.

Effect of lipopolysaccharide (LPS) on the antioxidant enzyme system activity of erythrocytes and phagocytes of carps in in vivo studies

The purpose of this experiment was to estimate the activity of antioxidant enzymes (SOD, GPx, CAT) in erythrocytes and phagocytes of carps (Cyprinus carpio L.) after intraperitoneal injection of LPS at a dose of 75 μg/100 g b.w. Enzyme activity was determined 3, 6 and 12 hours, as well as 3, 7, 14 and 28 days after LPS administration. After 3 and 6 hours, SOD in erythrocytes increased, respectively, to 188% and 142% of its control group level, and after 12 hours, SOD activity was significantly reduced (117%) and remained unchanged until the end of the experiment. From 12 hours after LPS administration until the end of the study, the PGx level was statistically significantly lower than in the control group, whereas the catalase activity was statistically significantly lower than in the control group in all study periods. In kidney phagocytic cells, SOD activity after 12 hours and 3 days was similar to that in the control group, and in the following study periods it amounted to 66-78% of the control values. Until the 14th day of observation, PGx activity was statistically significantly lower than it was in the control group. Catalase activity in kidney leukocytes was statistically significantly lower than in the control group during the entire experiment, and the lowest in the first study days, amounting to 48-42% of the control group value. The results indicate a long-term decrease in antioxidant enzyme activities in the experimental fish (lasting 14 or 28 days)...

Endothelial permeability, LDL deposition, and cardiovascular risk factors—a review

Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of enzymatic systems leading to ROS overproduction, proatherogenic factors lead to a pro-inflammatory status that translates in changes in gene expression and functional rearrangements, including changes in the transendothelial transport of molecules, leading to the deposition of low-density lipoproteins (LDL) and the subsequent infiltration of circulating leucocytes in the intima. In this review, we focus on such early changes in atherogenesis and on the concept that proatherogenic stimuli and risk factors for cardiovascular disease, by altering the endothelial barrier properties, co-ordinately trigger the accumulation of LDL in the intima and ultimately plaque formation.

An investigation of the mechanism of dexmedetomidine in improving postoperative cognitive dysfunction from the perspectives of alleviating neuronal mitochondrial membrane oxidative stress and electrophysiological dysfunction.

The aim of this study was to investigate the mechanism of dexmedetomidine in improving postoperative cognitive dysfunction from the perspectives of alleviating neuronal mitochondrial membrane oxidative stress and electrophysiological dysfunction. A total of 120 patients undergoing elective surgery under general anesthesia from June 2013 to May, 2016 were selected as the subjects of the study and randomly divided into the propofol + remifentanil and dexmedetomidine groups. The Rey Auditory Verbal Learning Test (AVLT) and Beck Depression Inventory (BDI) were performed at day 1 before operation and at day 1, 3, 5 and 15 after operation. The mitochondrial membrane potential was detected using a flow cytometer after staining and labeling for mitochondria in leukocytes via JC-1 fluorescence staining using a fluorescence probe at day 1 before operation and at day 1, 3, 5 and 15 after operation. The activities of mitochondrial respiratory chain complexes at day 1 before and after operation were detected via enzyme-linked immunosorbent assay (ELISA). The results showed that there were no statistically significant differences in the comparisons of general conditions (age, body weight, sex ratio, body mass index, anesthesia time, operation time, and length of stay in the ICU and hospital) for the dexmedetomidine and propofol + remifentanil groups (P>0.05). At day 3 and 5 after operation, the National Institutes of Health Stroke Scale (NIHSS) scores and AVLT scores in the two groups were decreased in different degrees, but the decrease range in the dexmedetomidine group was smaller than that in the propofol + remifentanil group, and the differences were statistically significant (P<0.05). At day 3, 5 and 15 after operation, the BDI scores of the two groups were increased in different degrees, but the increase range in the dexmedetomidine group was smaller than that in the propofol + remifentanil group, and the differences were statistically significant (P<0.05). At day 1, 3 and 5 after operation, the mitochondrial membrane potentials of the two groups were decreased in different degrees, but the decrease range in the dexmedetomidine group was smaller than that in the propofol + remifentanil group, and the differences were statistically significant (P<0.05). The mitochondrial membrane potentials of the two groups returned to the preoperative levels at day 15 after operation. The activities of mitochondrial respiratory chain complex I–IV in the propofol + remifentanil group at day 1 after operation were significantly decreased compared with those before operation, and the differences were statistically significant (P<0.05). The decrease in activities of mitochondrial respiratory chain complex I–IV in the propofol + remifentanil group at day 1 after operation was more significant than that in the dexmedetomidine group, and the difference was statistically significant (P<0.05). The results suggest that dexmedetomidine can relieve neuronal damage that may be caused by mitochondrial membrane oxidative stress, alleviate the damage to mitochondrial related enzyme system activity, and reduce the damage to the activities of mitochondrial respiratory chain enzyme complex I, II, III and IV, ultimately improving the postoperative cognitive dysfunction of patients.

Selenopheno quinolinones and coumarins promote cancer cell apoptosis by ROS depletion and caspase-7 activation

AimThis study was designed to investigate the mechanism underlying cancer cell apoptosis caused by selenophenoquinolinones and coumarins. Materials and methodsTwelve derivatives were studied according to their ability to suppress the proliferation of cancer cells in vitro (i.e., HepG2, MH-22A, MCF-7), induce cell apoptosis, modulate cellular antioxidant enzyme system activities (i.e., SOD, GPx, TrxR), influence the level of ROS, and modulate caspase activity. ResultsA plausible mechanism of apoptosis is presented. The lack of change in the activity of caspase-8 demonstrates that these compounds affect the intrinsic rather than the extrinsic pathway; moreover, the absence of caspase-9 activation suggests that the studied compounds are involved in the intrinsic pathway of apoptosis in a non-canonical manner. Provisionally, the increase in Smac/Diablo released from the mitochondria removes the inhibitory effect and activates caspase-7, leading to apoptosis. Additionally, the activation of caspase-1 activates effector caspase-7, thereby increasing the amount of cytochrome c and Smac/Diablo released from the mitochondria and ultimately leading to apoptosis. ConclusionThis present study provides scientific evidence that selenopheno quinolinones and coumarins promote cancer cell apoptosis by ROS depletion and caspase-7 activation in malignant cells.