Altered Enzyme Activity Research Articles

Possible protective activity of n-acetyl cysteine against cisplatin‑induced hepatotoxicity in rats.

CP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic effects. The present study aimed to reveal the effects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological findings. Twenty-eight wistar rats were randomly divided into four groups of seven animals. A dose of saline was administered (i.p.) to the control group for 5 days. One dose of NAC (200 mg/kg) was administered to the NAC group for 5 days (i.p.). To the NAC + CP group, a dose of CP (7.5 mg/kg) was administered on days 2 and 5 of the experiment, a dose of NAC (200 mg/ kg) (i.p.) was administered for 5 day of the experiment. CP (7.5 mg/kg) was administered to the CP group on days 2 and 5 of the experiment. At the end of the experiment, the biochemical, histological, and mRNA expression analyses of the liver tissues isolated from all the rats were performed. A statistically significant decrease was observed in the AST and ALT enzyme activities in Group NAC + CP compared to Control and CP groups. In addition, it was determined that the NAC administration reduced CP-induced inflammation by increasing the level of NF-κB and decreased CP-caused oxidative stress by decreasing the GPx level. Moreover, the histopathological analyses showed that NAC improved liver morphology. It was revealed by Western blotting analysis that NAC promoted Bcl-2 signaling and decreased p53 signaling. The findings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an effective part in the regulation of apoptotic markers.

The Potential Predictors in Chemotherapy Sensitivity.

Monitoring of patient and tumor during chemotherapy is important to determine whether the chemotherapy is effective to the patient. Variants affect drug enzyme activities and altered enzyme activities can be potential predictors for chemotherapeutic agents including cyclophosphamide and paclitaxel. Response to chemotherapy is primarily based on somatic mutations but germline variants may predict cancer cell sensitivity to chemotherapeutic agents. Furthermore, patient's genetic variation of immune system was reported to be associated with drug response and toxicity. Recently, the somaric and germilne genomic variation influences the pharmacokinetics of chemotherapy and these variation can be biomarkers for chemotherapy.

Plasma Carboxyl-Metabolome Is Associated with Average Daily Gain Divergence in Beef Steers.

Simple SummaryIn this study, we analyzed the plasma carboxyl-metabolome in beef steers with divergent average daily gain (ADG). Several short chain fatty acids were greater in beef steers with greater ADG. Conversely, several long chain fatty acids were greater in beef steers with lower ADG. Pathway analysis of the differential metabolites revealed alterations in abundance/activities of enzymes involved in fatty acid metabolism in the liver. The results of this study demonstrated that beef steers with divergent ADG had altered plasma carboxyl-metabolome, which is possibly caused by altered abundances and/or activities of enzymes involved in fatty acid oxidation and biosynthesis.We applied an untargeted metabolomics technique to analyze the plasma carboxyl-metabolome of beef steers with divergent average daily gain (ADG). Forty-eight newly weaned Angus crossbred beef steers were fed the same total mixed ration ad libitum for 42 days. On day 42, the steers were divided into two groups of lowest (LF: n = 8) and highest ADG (HF: n = 8), and blood samples were obtained from the two groups for plasma preparation. Relative quantification of carboxylic-acid-containing metabolites in the plasma samples was determined using a metabolomics technique based on chemical isotope labeling liquid chromatography mass spectrometry. Metabolites that differed (fold change (FC) ≥ 1.2 or ≤ 0.83 and FDR ≤ 0.05) between LF and HF were identified using a volcano plot. Metabolite set enrichment analysis (MSEA) of the differential metabolites was done to determine the metabolic pathways or enzymes that were potentially altered. In total, 328 metabolites were identified. Volcano plot analysis revealed 43 differentially abundant metabolites; several short chain fatty acids and ketone bodies had greater abundance in HF steers. Conversely, several long chain fatty acids were greater in LF steers. Five enzymatic pathways, such as fatty acyl CoA elongation and fatty-acid CoA ligase were altered based on MSEA. This study demonstrated that beef steers with divergent ADG had altered plasma carboxyl-metabolome, which is possibly caused by altered abundances and/or activities of enzymes involved in fatty acid oxidation and biosynthesis in the liver.

Effect of lycopene on hepatotoxicity induced by perfluorooctane sulfonic acid in rats

Objective: Intend to observe the liver injury induced by perfluorooctane sulfonic acid (PFOS) in SD rats and the protective effect of lycopene (LP) and its possible mechanism. Methods: 48 SD rats were randomly divided into 8 groups. The solvent control group of LP protection group and LP protection low, middle and high dose PFOS exposure groups were given LP suspension once a day according to their designed dose. The contents of ALT, ASP and AST in serum, the content of MDA in liver tissue and the activity of SOD and GSH-Px in liver tissue were measured after 2 months. Results: The levels of serum ALT, AST and serum ASP enzyme activity in middle and high dose PFOS groups and high dose PFOS groups were significantly higher than those in solvent control group (P < 0 05).The levels of serum ALT, ALP and AST in middle and high dose PFOS groups protected by LP were lower than those in the same dose PFOS group (P < 0 05). The content of MDA in liver tissue of rats treated with LP was significantly lower than that of rats exposed to the same dose of PFOS (P < 0.05). The contents of GSH-Px and SOD in the liver homogenate of the low, middle and high dose PFOS groups decreased compared with the solvent control group. Conclusion: PFOS can induce liver injury in rats, and lycopene can antagonize liver injury induced by PFOS through antioxidant mechanism.

Metabolite alteration in response to low phosphorus stress in developing tomato fruits

Alteration of fruit quality caused by environmental stress is a common but largely unresolved issue for plant cultivation and breeding practices. Phosphorus (P) deficiency may interfere with a variety of metabolic processes whose intermediate products are correlated with important fruit quality traits. However, how low P stress affects fruit quality has not been investigated in detail. In this study, we assessed the contents of major metabolites associated with tomato fruit quality under two low P treatments that started at the seedling or flowering stage. The major pigments and the key organic acids related to fruit sourness were differentially over-accumulated as fruit ripened under two low P treatments compared to those under the control treatment, while the total content of soluble sugars contributing to fruit sweetness was substantially reduced under both treatments. These changes were largely attributed to the alteration of enzyme activities in the relevant metabolic pathways. In particular, we found that low P stress from different developmental stages had differential effects on the activation of γ-aminobutyric acid shunt that were likely responsible for the preferential accumulation of different organic acids in tomato fruits. Our study suggested that low P stress strongly affected tomato fruit quality and the effects appeared to be variable under different regimes of low P conditions.

Metabolic Disturbance in Patients with Muscular Dystrophy and Reflection of Altered Enzyme Activity in Dystrophic Muscle: One Critical View

Muscular dystrophies are inherited myogenic diseases and considered by progressive muscle wasting and weakness with variable distribution and severity. The essential characteristics of muscular dystrophies are selective involvement, significant wasting and weakness of muscles. The most common and frequent types of muscular dystrophies are Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Facioscapulohumeral Dystrophy (FSHD) and Limb Girdle Muscular Dystrophy (LGMD). Metabolic disturbance is observed in muscular dystrophy patients (DMD, BMD, FSHD and LGMD-2B). Alteration in the level of metabolites (BCAA, Glu/ Gln, Ace, alanine, glucose, histidine, propionate, tyrosine and fumarate) in dystrophic muscle reflects the alteration in the activity of enzymes. Collectively, these observations propose that there is alteration in the rate of glycolysis, TCA cycle, fatty acid oxidation, gluconeogenesis pathway and protein metabolism (catabolism &amp; anabolism) in the muscular dystrophy patients. Metabolic disturbance, further provide the explanation about the pathophysiology of muscular dystrophy.

Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction

ABSTRACT Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.

Токсикодинаміка за сумісної дії хлорпірифосу та івіну при тривалому надходженні до організму

The combined action of pesticides is one of the problems of toxicology, because in comparison to individual active substances, their mixtures can increase toxicity and delayed action effects, which is a risk to human health. It is known that plant growth regulators (PGR) when applied together with pesticides help to reduce the quantitative rates of pesticides applied, the accumulation of pesticides and heavy metals in plants, reduce the acute toxicity of xenobiotics. The combined effect of the prolonged admission of PGRs and pesticides is an unexplored area, and it is an important issue in preventive toxicology. The Aim of the Research. Determination of the nature of toxic effects of Chlorpyrifos and “Ivin” combined action at subchronic oral admission. Materials and Methods. Chlorpyrifos and PGR “Ivin” (2.6-dimethyl-N-pyridine oxide) combined action was studied on male Wistar Han rats. Substances were administered orally, via a feeding tube for 13 weeks; Chlorpyrifos was administered in the form of an aqueous emulsion with an auxiliary material OP-10 at a dose of 5 mg/kg (1/15 LD50), “Ivin” — in the form of an aqueous solution at a dose of 13 mg/kg and 0.013 mg/kg (1/100 and 1/100000 LD50 respectively), the control group of rats was given water with an auxiliary material OP-10. Signs of intoxication were recorded, body weight was measured in 4, 9 and 13 weeks, biochemical indicators of blood serum were determined (the activity of ALT and AST enzymes and alkaline phosphatase; the content of crude protein, urea, cholesterol, triglycerides and glucose were determined using kits of reagents by BioSystems (Spain); cholinesterase (ChE) activity in serum, red blood cells and brain tissue was determined with the use of methodology by Hesrtin S. using a kit of reagents produced by LLC NPP Filisit-Diagnostics (Ukraine). Results. No clinical signs of intoxication were detected in the experimental groups of rats. Under the isolated use of Chlorpyrifos a significant decrease in body weight, ChE inhibition activity in all bio substrates, with the greatest effect in the brain (by 48.8%); increase (after 9 and 13 weeks) in the activity of ALT and AST by 26.7–32.6%, 12.5–12.0%; a slight but a significant increase in the level of urea and glucose in blood serum to 17.3% and 17.6 %, respectively was detected. Under the combined action of Chlorpyrifos and “Ivin” in specified doses the body weight of rats was at control level, decrease of ChE activity was observed in all biological substrates and was at nearly the same level with the isolated use of Chlorpyrifos. There was a tendency towards the decline in ChE inhibition activity in brain tissue, and under the combined action of Chlorpyrifos with “Ivin” at higher doses after 4 weeks this effect was a significant (22.15%, p &lt; 0.05). Conclusions. Chlorpyrifos under the isolated oral admission for 13 weeks has a weak hepatotoxic effect, as evidenced by the increase in cytolysis enzymes and urea levels in serum and causes a moderate anticholinesterase effect. “Ivin” under combined with Chlorpyrifos admission to the organism eliminates the hepatotoxic effects of Chlorpyrifos and reduces its anticholinergic effects in brain, which contributes to a less severe intoxication. Key Words: Chlorpyrifos, Ivin, hepatotoxic effect, anticholinesterase effect.

SIGNIFICANCE OF CLINICAL AND LABORATORY MARKERS IN DISORDERS OF THE FUNCTIONAL CONDITION OF THE HEPATOBILIARY SYSTEM IN NEONATAL JAUNDICE

INTRODUCTION: The liver is the central organ of metabolic activity in the body.&#x0D; OBJECTIVES: The purpose of this study was to determine predictors, major clinical features, and laboratory criteria for the severity of disorders of the functional state of the hepatobiliary system in newborns with neonatal jaundice (NJ). The study included 164 full-term infants. The main group - 92 children, with manifestations of pathological jaundice, was divided into two subgroups, depending on the severity of the pathology, considering concomitant perinatal pathology. IA group (46 children) includes children, condition of which was defined as moderate, IB (46 children) – children, condition of which was defined as severe, the control group consisted of 72 healthy term infants.&#x0D; METHODS: The complex of examination methods includes: collection of anamnesis of antenatal and perinatal periods in the mother, clinical examination of the newborn and laboratory methods of examination: blood biochemical analysis (TSB blood, bilirubin fractions, activity of ALT enzymes, AST, ALP , γ-GT, glucose level of blood serum, cholesterol, triglycerides) ultrasound examination of infants' liver.&#x0D; RESULTS: Clinical symptoms that confirmed the functional impairment of the hepatobiliary system (HBS) in newborns who had signs of NJ in perinatal pathology are: hepatosplenomegaly, impaired bowel function, hypoglycemia, anemic syndrome, hemorrhagic disorders. The results of biochemical studies of the blood showed an increase in the severity of the pathology, an increase in the level of TSB and the fraction of indirect bilirubin, activation of the cytolysis markers of ALT and AST, increase of LDH activity, decrease in the activity of g-GT and ALP, as well as decrease in the level of total protein, albumin, glucose, increase in the level of urea, cholesterol and triglycerides. The most explicit manifestations of HBS dysfunction were found in newborns with a severe condition at birth and in the early neonatal period caused both by the NJ and other comorbidities. Taking into account the revealed deepening of biochemical changes in indicators of blood serum in correlation with the increase of clinical manifestations of pathology, the diagnosis of changes in the early stages will allow to diagnose in time the disorders of the functional state of HBS in NJ for the purpose of appropriate therapeutic correction.&#x0D; CONCLUSION: The results of the analysis of anamnestic and clinical-laboratory parameters in newborns with NJ showed on the background of a clinical signs of dysfunction of the hepatobiliary system, the presence of significant biochemical changes, especially enzymatic activity, including, ALT, AST, LDH, ALP, and g-GT and, also an increase in TBS levels and an indirect bilirubin fraction, a decrease in total protein and albumin, glucose, a rise in urea, cholesterol and triglycerides.&#x0D; The use of a biochemical markers in newborns with clinical manifestations of neonatal jaundice, especially in cases of significant severity of the condition with concomitant perinatal pathology, requires more detailed analysis in order to determine the main pathogenesis of disorders of the functional state of the hepatobiliary system for the purpose of timely correction and improvement of the outcome of treatment.

Folic acid and vitamin B12 ameliorate nicotine-induced testicular toxicity in rats

Introduction and Aim: Cigarette smoking, one of the fundamental roots of preventable morbidity, has a myriad of notorious effects. Nicotine is the most bountiful and symbolic constituent of cigarette smoke. The liaison between smoking and infertility has been investigated for decades; but it’s still dubious whether the noxious effects of cigarette smoking on testis and sperm characteristics are by virtue of nicotine. Therefore, the current study interrogated the ameliorative effects of folic acid and vitamin B12 on nicotine induced catastrophe in testicular tissue and sperm characters in male albino rats.&#x0D; Materials and Methods: Rats were treated with nicotine (3 mg/kg body weight/day, intraperitoneal) with or without folic acid (36µg/kg body weight/day, orally) and vitamin B12 (0.63µg/kg body weight/ day, orally) for 21 days. Sperm qualities were analyzed for motility and morphology. Various oxidative and anti- oxidative stress parameters, pro inflammatory cytokines levels, hormonal assays were performed.&#x0D; Results: Findings marked that nicotine caused degenerative changes in the testicular tissue. Supplementation with folic acid and vitamin B12 reversed these results along with suppressing the nicotine induced changes in TNF- ?, IL-6, and markers of oxidative stress. Moreover, folic acid and vitamin B12 in combination also significantly blunted the altered activities of testicular key androgenic enzymes, plasma levels of testosterone, LH, and FSH following nicotine exposure.&#x0D; Conclusion: In closure, testimonies manifested that folic acid and vitamin B12 may act as plausible strategy against oxidative stress, which is a pivotal step in nicotine-induced reproductive toxicity, and bettering functional status of testicular tissue by scavenging free radicals and hindering the generation of pro- inflammatory cytokines.&#x0D;

How the Pacific Oyster Responds to Ocean Acidification: Development and Application of a Meta-Analysis Based Adverse Outcome Pathway

Biological fitness relies on processes acting at various levels of organization, all of which can be modified by environmental change. Application of synthesis frameworks, such as the Adverse Outcome Pathway (AOP), can enhance our understanding of the responses to stressors identified in studies at each level, as well as the links among them. However, the use of such frameworks is often limited by a lack of data. In order to identify contexts with sufficient understanding to apply the AOP framework, we conducted a meta-analysis of studies considering ocean acidification effects on calcifying mollusks. Our meta-analysis identified that most studies considered the adult life history stage, bivalve taxonomic group, individual-level changes, as well as growth and metabolism related responses. Given the characteristics of published literature, we constructed an AOP for the effects of ocean acidification on calcification in an adult bivalve, specifically the Pacific oyster (Magallana gigas). By structuring results within the AOP framework we identify that, at present, the supported pathways by which ocean acidification affects oyster calcification are via the downregulation of cavortin and arginine kinase transcription. Such changes at the molecular level can prompt changes in cellular and organ responses, including altered enzyme activities, lipid peroxidation, and regulation of acid-base status, which have impacts on organism level metabolic rate and, therefore, calcification. Altered calcification may then impact organism mortality and population sizes. We propose that where developed and incorporated in future studies, the AOP framework could be used to investigate sources of complexity including varying susceptibility within and among species, feedback mechanisms, exposure duration and magnitude, and species interactions. Such applications of the AOP framework will allow more effective reflections of the consequences of environmental change, such as ocean acidification, on all levels of biological organization.

Prepubertal exposure to arsenic alters male reproductive parameters in pubertal and adult rats

Arsenic induces reproductive disorders in pubertal males after prepubertal exposure. However, it is unclear the extent to which those effects remain in testis and epididymis of sexually mature rats after arsenic insult. This study evaluated the effects of prepubertal arsenic exposure in male organs of pubertal rats, and their reversibility in adult rats. Male pups of Wistar rats on postnatal day (PND) 21 were divided into two groups (n = 20/group): Control animals received filtered water and exposed rats received 10 mg L‐−1 arsenic from PND 21 to PND 51. At PND 52, testis and epididymis of ten animals per group were examined for toxic effects under morphological, functional, and molecular approaches. The other animals were kept alive under free arsenic conditions until PND 82, and further analyzed for the same parameters. Pubertal rats overexpressed mRNA levels of SOD1, SOD2, CAT, GSTK1, and MT1 in their testis and SOD1, CAT, and GSTK1 in their epididymis. In those organs, catalase activity was altered, generating byproducts of oxidative stress. The antioxidant gene expression was unchanged in adult rats in contrast to the altered activity of antioxidant enzymes. Histological alterations of testis and epididymis tissues were observed in pubertal and adult rats. Interestingly, only adult rats exhibited a remarkable decrease in serum testosterone levels. Prepubertal exposure to arsenic caused morphological and functional alterations in male reproductive organs of pubertal rats. In adult rats, these damages disappeared, remained, get worsened, or recovered depending on the parameter analyzed, indicating potential male fertility disorders during adulthood.

Changes in antioxidant enzyme activities and metabolic parameters in dairy cows during different reproductive periods

Our study aimed to monitor the alterations in antioxidant enzyme activities and the metabolic profile parameters and their relationships in dairy cows during different reproductive stages (gestational-, dry-, pre- and post-partum). The collection of blood samples from thirty healthy pregnant Holstein cows took place at a commercial dairy farm, between September 2015 and June 2016. The cows covered eight different reproductive stages (4–6 weeks before the dry period (D4-6w)), at the beginning of the dry period (D0; on day 210 of gestation), the first month of the dry period (D1m), antepartum day 8 (APd8), postpartum (PP) day 3 (PPd3), PP day 8 (PPd8), PP between 3rd-4th weeks (PP3-4w) and PP between 80 and 90 days (PP80-90d). The activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were analysed to monitor and evaluate the antioxidant system. Concentrations of beta-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFA), albumin, glucose, total bilirubin, cholesterol, calcium (Ca) and the enzyme activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (GGT) were also determined as metabolic profile parameters. GPx activities increased in D1m (P < 0.05) and peaked during the PP3d and PP8d periods (P < 0.0001), with values decreasing again at the PP3-4w period. The most significant change in SOD activities was detected in the PP3-4w with a significant decrease (P < 0.05). BHBA and NEFA concentrations increased significantly during the PPd3 and PPd8 periods (P < 0.05), with BHBA decreased to low values in the PP3-4w (P < 0.05). Significant positive correlations were found between BHBA, NEFA, total bilirubin and GPx (0.784, 0.874 and 0.871; P < 0.05, P < 0.01 and P < 0.01 respectively). A significant negative correlation between calcium and cholesterol and GPx was found (−0.857, P < 0.01; and −0.681, P < 0.05, respectively). As a result, a relationship was determined between blood antioxidant enzymes and metabolic parameters at different periods. High GPx and SOD activities, especially in the early period before and after parturition, is thought to be related to the adaptation of the animals to this process. The lack of adaptation abilities of animals during these periods causes many problems seen during early postpartum. Therefore, considering GPx and SOD activity measurements in pre- and postpartum periods contributes to better management of these periods and the prevention of complications.

Monitoring the Redox Status in Multiple Sclerosis.

Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

Mechanisms associated with pyrethroid resistance in populations of Aedes aegypti (Diptera: Culicidae) from the Caribbean coast of Colombia.

Aedes aegypti is the main vector of dengue, chikungunya, and Zika viruses, which are of great public health importance in Colombia. Aedes control strategies in Colombia rely heavily on the use of organophosphate and pyrethroid insecticides, providing constant selection pressure and the emergence of resistant populations. In recent years, insecticide use has increased due to the increased incidence of dengue and recent introductions of chikungunya and Zika. In the present study, pyrethroid resistance was studied across six populations of Ae. aegypti from the Caribbean coast of Colombia. Susceptibility to λ-cyhalothrin, deltamethrin, and permethrin was assessed, and resistance intensity was determined. Activity levels of enzymes associated with resistance were measured, and the frequencies of three kdr alleles (V1016I, F1534C, V410L) were calculated. Results showed variations in pyrethroid susceptibility across Ae. aegypti populations and altered enzyme activity levels were detected. The kdr alleles were detected in all populations, with high variations in frequencies: V1016I (frequency ranging from 0.15–0.70), F1534C (range 0.94–1.00), and V410L (range 0.05–0.72). In assays of phenotyped individuals, associations were observed between the presence of V1016I, F1534C, and V410L alleles and resistance to the evaluated pyrethroids, as well as between the VI1016/CC1534/VL410 tri-locus genotype and λ-cyhalothrin and permethrin resistance. The results of the present study contribute to the knowledge of the mechanisms underlying the resistance to key pyrethroids used to control Ae. aegypti along the Caribbean coast of Colombia.

Caffeic and chlorogenic acids modulate altered activity of key enzymes linked to hypertension in cyclosporine-induced hypertensive rats.

This study aimed to explore the protective mechanism of caffeic acid (CAA) and chlorogenic acid (CHA) on cyclosporine (CSA) induced hypertensive rats. Effect of CAA and CHA on diastolic blood pressure (DBP), mean arterial pressure (MAP), angiotensin-converting enzyme (ACE), e-nucleotide triphosphate dephosphorylase (e-NTPDase), 5' nucleotidase and adenosine deaminase (ADA) activity in CSA-induced hypertensive rats were determined. CAA and CHA administration stabilized hypertensive effect caused by CSA administration. Also, altered activity of ACE (lung), e-NTPDase, 5' nucleotidase, ADA as well as elevated malondiadehyde (MDA) level was restored in all the treated hypertensive rats in comparison with the untreated hypertensive rats. Hence, these observed results could underlie some of the mechanisms through which CAA and CHA could offer antihypertensive effect.

Decrease of catalytic efficiency of Photinus pyralis firefly luciferase in the presence of graphene quantum dots

Objective(s): Firefly luciferase is a monooxygenase enzyme that emits flash of light during the enzymatic reaction. Luciferase has been used in many bioanalytical fields from ATP detection methods to in vivo imaging. In recent decades, focus has been carried out on nanoparticles for their fluorescence properties. Semiconductor quantum dots have unique tunable properties that turn them promising tools in biological and biomedical researches, as nanosensors, photo-electrochemical and light-emitting devices. Carbon-based nanoparticles such as graphene quantum dots (GQDs) have useful benefits such as low toxicity, suitable luminescence and easy preparation. Materials and Methods: In this study, recombinant P. pyralis luciferase was expressed and purified based on N-terminal His-tag and then kinetic parameters of enzyme activity such as Km and Vmax values in presence and absence of GQDs were calculated. Results: The results showed that Km for ATP and luciferin substrates in the presence of GQDs were increased. Fluorescence spectroscopy showed significant changes in protein structure or in fluorescence spectra and decrease in the activity of the luciferase in presence of GQD. Both loss of activity and increase of substrates Km showed decrease of catalytic efficiency presumably through structural alteration. Conclusion: From these data it can be concluded that the protein structure under the influence of GQD may have changed that lead to alteration of enzyme activity.

Safety Evaluation of Picralima nitida (Akuamma) Seed Extracton Hepatorenal and Haematological Systems of Rats

Background: Plants like herbs has been extensively used for different kinds of nutritional and medicinal purposes, however, scientific studies has shown that these medicinal plants may have deleterious effects on some vital organs of the body if not taken at the recommended doses. Thus, there is a need for safety evaluation of these plants to ascertain their actions on organ’s physiological functions. This present study evaluates the effects of ethanol seed extract of Picralima nitida on the haematological examines and some enzymes activities in the serum of albino rats. Twenty-five rats were equally randomized into five groups. Group A (control) received distilled water while graded doses (50, 100, 150 and 200 mg/kg body weight) of ethanol seed extract of Picralima nitida were administered to rats in groups B, C, D and E respectively for 14 days. Haematological studies were carried out on the rats’ blood samples while concentrations of total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine were measured in the serum. Results: Result obtained revealed that treatment of rats with various graded doses of ethanol seed extract of Picralima nitida caused marked increase in urea and creatine compared to the control. Rats treated with 150 and 200mg/kg bw of the extract showed marked elevation in serum levels of the enzymes suggesting that the extract may have adverse effects at this dose. There was also a marked elevation in serum electrolytes of rats treated with 150 and 200mg/kg bw of the extract. Rats treated with low concentrations (50 and 100 mg/kg bw) of the extract demonstrated no marked differences or alteration in haematological parameters, protein profile and enzyme activities in the serum. Conclusion: The results of this study indicated that consumption of ethanol seed extract of Picralima nitida as a therapeutic treatment is nontoxic at lower dose. However, if taken at high doses, the extract might be detrimental to some vital organs and systems.

Alterations in Enzyme Activity of Carbonic Anhydrase, 6-phosphogluconate Dehydrogenase and Thioredoxin Reductase in Rats Exposed to Doxorubicin and Morin

Objective: Carbonic anhydrase (CA), 6-phosphogluconate dehydrogenase (6PGD) and thioredoxin reductase (TrxR) enzymes are the essential biological molecules needed for metabolic processes in all living cells. This study was designed to investigate the activities of CA, 6PGD and TrxR enzymes in the brain, kidney, liver, heart and testis tissues of the rats exposed to Dox and morin. Methods: Male Wistar albino rats were randomly divided into three groups as control, morin and DOX, each of them containing 7 rats. At the end of the experimental procedure, CA, 6PGD and TrxR enzyme activities in tissues of rats were determined spectrophotometrically. Results: In our study, we observed that DOX activated CA enzyme in liver and kidney tissues while inhibiting CA enzyme in the other tissues, activated 6PGD enzyme in the kidney, liver and heart tissues, and inhibited the TrxR enzyme in all the tissues. In addition, morin activated CA enzyme in the liver tissue while inhibiting CA enzyme in the brain, heart and testis tissues. Morin activated 6PGD enzyme activity while it inhibited TrxR enzyme in all the tissues. Conclusion: The findings showed that doxorubicin and morin had similar properties in the tissues as to their effect on enzyme activities.

Efficiency Research of the Beverage Based on the Still Mineral Water and BAD “Eramin”

The article presents analysis results of the actual consumption of drinking water and sport drinks by athletes before and after training and concerns the effectiveness study of the drink based on non-carbonated mineral drinking water “ARDVI” and dietary supplement “Eramin”. Analysis of liquid consumption by sportspeople before and after training shows that all athletes participating in the experiment (100,0 %) consume bottled drinking water for dehydration. The maximum consumption of bottled water is 1 500 ml, the minimum – 150 ml; the amount of tea drunk by judoists equal 500 ml with an average amount of 324 ml; carbonated drinks (“Coca-Cola”, “Sprite”, etc.) athletes do not use. The authors suggested judo athletes to replace 500 ml of bottled water with 500 ml of a drink based on the mineral water “ARDVI” and the biologically active supplement “Eramin”. According to the results of preclinical research conducted on rats, the introduction of this drink to animals through a probe contributes to the muscle and epithelial tissues regeneration. When studying the testosterone and cortisol amount in the blood of athletes, authors found that on the 90th day of taking a drink based on mineral water “ARDVI” these indicators were 84.2 ± 0.6 and 35.1 ± 0.8 nmol/l, respectively; and in the first group – 71.3± 0.5 and 26.4± 0.4 nmol/l, which is 18.1 and 33.0 % higher than in the control group. An increase in the number of studied hormones in the blood of athletes can indicate an increase in physical performance and a decrease in fatigue. Researchers noted a high value of the creatine phosphokinase enzyme (137 units/l) in the blood serum of athletes in the control group, which indicates training intensity and the possibility of muscle tissue injury. In the blood of athletes of the experimental group, the amount of this enzyme is 85 units/l, which is lower than the control by 62.0 %. There was a significant decrease in the activity of AST and ALT enzymes by 15.8 and 22.0 % while consuming studied drink by athletes. At the same time, the muscle injury index corresponded to the norm. Athletes who took the sports drink under study had the optimal value of the de Ritis coefficient (1.33). Authors concluded that the athletes use of drink based on mineral water “ARDVI” and dietary supplement “Eramin” allows sportsmen to maintain performance, reduce fatigue and prevent muscle tissue damage, including the myocardium.