Gamma-glutamyltransferase Activity Research Articles

Haemato-chemical and immune variations in Holstein cows at different stages of lactation, parity, and age

Physiological components are influenced by various factors. However, little is comprehensively understood about lactation, parity, and age-related blood profile changes in dairy cows. Thus, we investigated significant variables associated with haemato-chemical and immune changes in healthy dairy cows. Blood was collected from 246 Holstein cows to analyse the physiological changes at different stages of lactation, parity, and age. The white blood cells (WBCs) and monocytes were influenced by the parity or age. Cows over three years of age showed a decreased WBC and monocyte count when compared to cows under three years of age. The lactation stage affected the red blood cell (RBC) profiles and metabolism, liver function-related components, and immunoglobulin A (IgA). A decrease in the haemoglobin (Hb) and haematocrit (HCT) were associated with peak lactation. The blood urea nitrogen (BUN) and total cholesterol (T-CHOL) concentrations, and alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) activities increased in peak or mid lactation and remained high up to late lactation. An increased serum IgA concentration was observed in early and mid-lactation compared to that in late gestation. Many components of the haemato-chemical and immunological profiles changed (Hb, HCT, BUN, T-CHOL, ALT, GGT, and IgA) at a specific lactation stage under the physiological conditions. These data revealed that the lactation stage was a major variable contributing to the physiological variations in the dairy cows. Therefore, the lactation stage should be considered when determining haemato-chemical and immunological abnormalities.

Opioid-like peptides and ghrelin mitigation of bariatric results depends on obesity level

Bariatric surgery, as the only effective treatment of obesity, has strong effects on the metabolism, and nervous and endocrine systems. Thus, based on the different opinions about the efficaciousness of morbid obesity treatments, the aim of the present study was to estimate the association of serum ghrelin and Met-enkephalin (native, five amino acids and cryptic, precursor of enkephalin) concentrations with body mass index (BMI) value in bariatric patients within 30 postoperative days. The study was performed on 38 female patients divided into two groups: I - BMI lower than 40 kg/m² (n = 18) and II - BMI higher than 40 kg/m² (n = 20). Blood was taken before (-24 h), and 72 h and 30 days after the sleeve gastrectomy. Routine haematological, anthropometric, and metabolic parameters as well as thyroid-stimulating hormone (TSH), ghrelin, and Met-enkephalin values were measured in all patients. There were statistically significant differences between the two groups before the surgery in terms of TSH, both forms of Metenkephalin, triglycerides concentrations, and activity of alanine transaminase (ALT), gamma glutamyltransferase (GGTP), and C-reactive protein (CRP). After 72 h, the serum levels of cryptic Met-enkephalin and CRP, and activity of enzymes varied between the two groups of patients. Thirty days after the surgery, some metabolic and immune parameters were still different in both female groups in favour of patients with lover BMI. However, significant differences were noticed in the levels of ghrelin (increase), and native (decrease) and cryptic Met-enkephalins (increase). The activity of endogenous peptides in bariatric patients is connected with the degree of obesity. Ghrelin level increases are negatively correlated with native Met-enkephalin changes shortly after bariatric surgery. The interplay of ghrelin and opioids might be considered as a predictor of postoperative weight loss success.

Blood collection from dairy calves at exsanguination post-slaughter yields similar biochemical and packed cell volume measurements compared with in vivo collection during lairage

Blood collection at exsanguination is a method of collecting samples at abattoirs which itself has no effect on animal welfare, compared with collection prior to stunning. However, there is the potential for artefact to affect measurements. It was hypothesised that, for most blood analytes measured, the differences between lairage and exsanguination measurements would be minimal, except for creatine kinase, which was expected be higher in exsanguination samples. Fifty-nine male dairy calves approximately 5–10 days old were sampled prior to slaughter, and again during exsanguination after stunning. Each sample was analysed for packed cell volume, serum urea, beta-hydroxybutyrate, gamma-glutamyl transferase, total protein, glucose and creatine kinase concentrations. Exsanguination and lairage blood results were compared using a paired t-test. There were no significant differences between the measurements taken at exsanguination compared with lairage for packed cell volume, urea and beta-hydroxybutyrate. Glucose concentrations were higher in exsanguination samples, and total protein concentrations were lower, but for both of these analytes the differences were clinically small. Gamma-glutamyl transferase activity was lower in exsanguination samples compared with lairage samples. Creatine kinase activity was higher in exsanguination samples. It was concluded that collecting blood at exsanguination is a valid method for collecting samples for measurement of packed cell volume, urea, and beta-hydroxybutyrate in calves. Glucose and total protein can also yield useful measurements in these samples, though care needs to be taken with interpretation given the minor differences between exsanguination and lairage measurements. Exsanguination samples may be unsuitable for creatine kinase and gamma-glutamyl transferase measurement.

Glutathione catabolism by Treponema denticola impacts its pathogenic potential

Treponema denticola is a spirochete that is etiologic for periodontal diseases. This bacterium is one of two periodontal pathogens that have been shown to have a complete three step enzymatic pathway (GTSP) that catabolizes glutathione to H2S. This pathway may contribute to the tissue pathology seen in periodontitis since diseased periodontal pockets have lower glutathione levels than healthy sites with a concomitant increase in H2S concentration. In order to be able to demonstrate that glutathione catabolism by the GTSP is critical for the pathogenic potential of T. denticola, allelic replacement mutagenesis was used to make a deletion mutant (Δggt) in the gene encoding the first enzyme in the GTSP. The mutant cannot produce H2S from glutathione since it lacks gamma-glutamyltransferase (GGT) activity. The hemolytic and hemoxidation activities of wild type T. denticola plus glutathione are reduced to background levels with the Δggt mutant and the mutant has lost the ability to grow aerobically when incubated with glutathione. The Δggt bacteria with glutathione cause less cell death in human gingival fibroblasts (hGFs) in vitro than do wild type T. denticola and the levels of hGF death correlate with the amounts of H2S produced. Importantly, the mutant spirochetes plus glutathione make significantly smaller lesions than wild type bacteria plus glutathione in a mouse back lesion model that assesses soft tissue destruction, a major symptom of periodontal diseases. Our results are the first to prove that T. denticola thiol-compound catabolism by its gamma-glutamyltransferase can play a significant role in the in the types of host tissue damage seen in periodontitis.

Serum gamma-glutamyltransferase activity and Parkinson\u2019s disease risk in men and women

We evaluated serum gamma-glutamyltransferase (GGT) and the risk of Parkinson’s disease (PD). Using data from the National Health Insurance Service (NHIS) database, we constructed a cohort consisting of individuals aged above 40 years who underwent a health check-up in 2009. After excluding individuals with heavy alcohol consumption, hepatobiliary and pancreatic disorders, and a previous history of PD, each quartile group of baseline serum GGT levels was monitored for the development of PD for 7 years. Adjusted hazard ratios (HRs) for PD were estimated by Cox proportional hazard models adjusting for potential confounding variables. We additionally analyzed the possible interaction between GGT and obesity or metabolic syndrome. Among the 6,098,405 individuals who were included, PD developed in 20,895 individuals during the follow-up (0.34%, 9,512 men and 11,383 women). The top quartile of serum GGT (geometric means, 90.44 IU/L in men and 41.86 IU/L in women) was associated with a lower risk in men (adjusted HR = 0.72 (95% CI: 0.67–0.76)) and a higher risk in women (adjusted HR = 1.30 (95% CI: 1.23–1.37)) using the lower GGT quartiles as a reference. Obesity and metabolic syndrome increased PD risk in both sexes, and there was only a subadditive interaction between serum GGT and obesity in women.

Correlation Between Gamma-Glutamyl Transferase Activity and Glutathione Levels in Molecular Subgroups of Breast Cancer.

The gamma-glutamyl cycle catalyzed by gamma-glutamyl transferase (GGT) plays an important role in glutathione (GSH) homeostasis in the cell. In cells continuously exposed to the drug, the main phase of the enzymatic detoxification is the conjugation of the drug with GSH catalyzed by glutathione-S-transferase (GST). Conjugation of drugs with GSH is the first step in the development of chemotherapeutic drug resistance. In this study, we aimed to investigate the relationship between GGT and GSH in molecular subgroups of breast cancer patients. Serum GGT activity and GSH levels for patients diagnosed with breast cancer (n=58) and healthy controls (n=8) were measured by a spectrophotometric method and a colorimetric kit, respectively. GGT activity was significantly higher in the total patient group and in the molecular subgroups than those in the control groups (p<0.05). Serum GSH levels were higher in the patient groups compared to controls without reaching statistical significance (p>0.05). GGT activity was positively correlated with GSH levels in the total patients and healthy controls (p<0.001 and p<0.05, respectively). There was also a positive correlation between GGT activity and GSH levels in Luminal A, HER2-positive (Human epidermal growth factor receptor 2), and Triple-negative groups (p<0.05). This is the first study showing the relationship between GGT and GSH in molecular subgroups of breast cancer. An increase in GGT activity may affect intracellular GSH synthesis. Therefore, having a correlation between GGT and GSH in some molecular subgroups may affect the course of treatment in these patients.

Are liver function biomarkers independently associated with Framingham risk score in women?

Introduction/Objective. Given the contradictory results regarding the association of liver function biomarkers [e.g., alanine-aminotransferase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin)] and the risk of cardiovascular disease (CVD), we aimed to explore the relationship between these biomarkers and Framingham risk score (FRS), an established tool used in the prediction of 10-year CVD risk in the cohort of women. Methods. A total of 278 women participated in this cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained. Results. There was a significant increase in ALT and GGT activity, as well as a decrease in total bilirubin level in the high-risk FRS group compared to moderate-, and low-risk FRS (p for trend = 0.025, p &lt; 0.001, p &lt; 0.001, respectively). Multivariate logistic regression analysis showed that body mass index, triglycerides, creatinine, and high sensitivity C-reactive protein levels were the independent predictors of FRS in women [odds ratio (OR) = 1.234, p = 0.001; OR = 2.856, p = 0.001; OR = 1.090, p = 0.002, and OR = 1.295, p = 0.045, respectively]. In contrast, total bilirubin, ALT and GGT lost their independent predictions for high CVD risk. Conclusion. Liver function biomarkers (i.e. ALT, GGT, and total bilirubin) are not independently associated with FRS. It seems that some other cardiometabolic disturbances might modulate this relationship.

Diagnosis and treatment of foreign bodies swallowing syndrome in camels (Camelus dromedarius) with special reference to the role of mineral deficiency.

This study describes the clinical presentation of ruminal and reticular foreign body syndrome (RRFBS), and evaluates the effect of mineral deficiency on its occurrence in dromedary camels. Thirty dromedary camels were divided into two groups. Group 1 (control) included 10 apparently healthy she-camels. Group 2 consisted of twenty dromedary camels diagnosed with RRFBS on the basis of clinical, ultrasonographic, hematological, and biochemical examinations. Clinical findings showed decreased appetite and milk yield, tympany, and gradual body weight loss. Ultrasonographic examinations revealed the presence of hyperechoic material with variable degrees of shadowing. Hematological evaluation showed a significant (P<0.05) decrease of the total erythrocyte and lymphocyte count and a significant increase of neutrophils in the camels with RRFBS compared to the controls. Biochemical tests showed a significant elevation in the activity of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatine kinase (CK), glucose, creatinine, and blood urea nitrogen and a significant decrease of sodium, chloride, potassium, cobalt, iron, and selenium in the camels with RRFBS compared to the controls. Rumenotomy was performed on the 20 camels as a surgical intervention for treating the RRFBS. By the 6th month postoperatively, all surgically treated camels had completely recovered except for one with tympany and slight swelling in situ. In conclusion, trace element deficiency might play an important role in the occurrence of foreign body ingestion syndrome in dromedary camels. Moreover, clinical, ultrasonographic, hematological, and biochemical examinations are considered as tools assisting in the accurate diagnosis, prognosis, and treatment stratagem for RRFBS in camels.

Evaluation of cysteine-stabilised peptide fraction of aqueous extract of Morinda lucida leaf for hepatotoxic effects in mice

Cysteine-stabilised peptide fraction of the aqueous extract of Morinda lucida leaf has been reported to exert diverse biological activities, but its effects on the liver have not been evaluated. This study was carried out to evaluate the effects of cysteine-stabilised peptide fraction (CSPF) of aqueous extract of Morinda lucida leaf on selected liver function indices in mice. Sixty mice were randomly divided into six groups of ten mice each. Mice in group A (control) were orally administered 5% DMSO while mice in groups B, C, D, E and F were orally administered 31.25, 62.5, 125, 250 and 500 mg/kg body weight of CSPF respectively. Half of the mice in the groups received the respective doses of CSPF for 7 days while the other half received them for 28 days, after which selected liver function indices in the serum and liver of the mice were determined. The results revealed that plasma alkaline phosphatase, gamma glutamyl transferase and glutamate dehydrogenase activities and plasma albumin, globulin, total bilirubin and conjugated bilirubin concentrations were not significantly (P&gt;0.05) altered after 7 and 28 days of CSPF administration at all doses compared to controls. However, liver alanine aminotransferase (ALT) activity was significantly reduced (p&lt;0.05) at doses of CSPF higher than 125 mg/kg body weight, with no corresponding alteration in serum ALT activity after 28 days of administration compared to controls. Thus, prolonged administration of high doses of CSPF may adversely affect the glucose-alanine cycle in the liver which is very important for glucose homeostasis during fasting.

Evaluation of salivary gamma-glutamyl transpeptidase as a biomarker in oral squamous cell carcinoma and precancerous lesions.

Background:Oral cancer is such a common malignancy, but its manifestations are usually asymptomatic, and by the time the lesion is diagnosed its invasion is deep. This makes the survival rate poor and also the treatment rendered during such stages is extensive and debilitating. In this regard, a novel approach has been advocated in the estimation of biomarkers in the body fluids. Gamma-glutamyl transpeptidase (GGT)/gamma-glutamyl transferase is an enzyme that is essential for the absorption of amino acids, especially in the degradation of glutathione. Its activity is increased in oral cancer and precancerous lesions.Aims and Objectives:The purpose of this study was to assess the activity and concentration of GGT in precancerous and cancerous patients in comparison with normal patients and also to assess its efficacy as an effective tumor marker.Materials and Methods:The study population comprised a total of 75 patients who were categorized into three groups as normal patients (25 cases in Group A), patients with precancerous lesions (25 patients in Group B) and patients with oral squamous cell carcinoma (25 cases in Group C). 5 ml of whole unstimulated saliva collection was done, it was centrifuged at 3000 rpm for 15 min and the supernatant thus obtained was used for the estimation of GGT levels. The detection was done by photometric method reading the absorbance at 405 nm.Results:Group A patients had values of GGT ranging from 4 to 30U/L with a mean of 16.7 ± 1.94U/L. Group B had activity of GGT ranging from 39 to 65 U/L with a mean of 50.4 ± 1.67U/L. In group C, the evaluated GGT activity was between 53 and 86 U/L and the mean was 70 ± 2.37 U/L. Statistical analysis using Chi-square test was conducted. Correlations between Group A and Group B and between Groups A and C showed a statistically significant relation (P < 0.005).Conclusion:Salivary gamma-glutamyl transferase activity can be used effectively as a tumor marker, and further studies with a larger sample size can be done to correlate this finding.

Study of the relationship between the age of the rams and the quality of their ejaculates obtained outside the breeding season

The present study aims to research the effect of age on the quality of ejaculates of rams from Synthetic population of Bulgarian dairy breed. Rams divided into two age groups were used for the experiment: G1 (2.5 years) versus G2 (6 years). Ejaculates were obtained by the method of artificial vagina and diluted with medium 6A-G. The tested ejaculates were obtained outside the breeding season. A Sperm Class Analyzer (SCA Microptic, Barcelona, Spain) was used to study sperm motility. The biochemical activity of the enzymes lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) was determined using an automatic Mindrai BA88 spectrophotometer. The activity of the enzymes was studied in sperm plasma, in aqueous and tritonic extract. Significant differences between the groups were found in total sperm motility (P?0.05) and LDH enzyme activity in sperm plasma (P?0.01). Regarding the efficiency of the LDH enzyme in aqueous and tritone extract, no significant differences between the groups was found. No significant differences were found between groups for GGT activity, while age had significant impact on LDH enzyme in sperm plasma.

Utility of serum gamma glutamyl transferase activity among hypertensive patients

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Hypertension, a chronic medical condition of elevated blood pressure in the arteries. It is an emerging problem worldwide and one of the identifiable cause of kidney disease. Gamma glutamyl transferase (GGT) plays essential role in the metabolism of glutathione which is reported as major antioxidant. More recently increased GGT is associated with pathogenesis of hypertension. This study was aimed to determine activity of gamma glutamyl transferase in hypertensive patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; All together 150 participants were recruited from Department of Medicine, Star Hospital for this hospital based cross-sectional study. Among which 50 were normotensive, 50 were pre-hypertensive and 50 were hypertensive. Blood sample were collected and analyzed in autoanalyser by enzymatic method. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Mean serum gamma glutamyl transferase activity is significantly different among normotensive, prehypertensive and hypertensive groups (i.e., 10.3 IU/l, 26.8IU/l and 37.2 IU/l respectively). Serum gamma glutamyl transferase activity is significantly higher in prehypertensive patients than normotensive group (p=0.001). Similarly GGT activity is significantly increased in hypertensive patients than prehypertensive patients (p=0.001).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Serum gamma glutamyl transferase activity is raised in prehypertensive and hypertensive participants as compared to normotensive. Thus Serum gamma glutamyl transferase level can have potential role on management of hypertension.&lt;/p&gt;

Validation of serum gamma-glutamyl transferase activity and body weight information for identifying dairy calves that are too young to be transported to auction markets in Canada

Dairy calves are at risk of being stressed when transported during the first week of life. A new Canadian federal rule will forbid transportation of calves younger than 9 d old to auction market. However, in the absence of reliable information to determine birth date, other indirect methods would be of interest. This study aimed to determine the prediction accuracy of body weight, Brix refractometry, and serum gamma-glutamyl transferase (GGT) activity for determining if a calf was not fit to be transported (i.e., <9 d old). For this purpose, we used 284 calves with a known birth date from a cross-sectional and a prospective cohort study. A logistic regression model was built based on multivariable analysis as well as a misclassification cost term analysis. Because of the collinearity between GGT activity and Brix value and lower discrimination of Brix value, the GGT activity was retained for the main model. The final logistic regression model contained body weight and log-transformed GGT activity value. The misclassifications of the logistic model was minimized using a model probability threshold ≥0.55 with a sensitivity of 70.4% and a specificity of 77.3%. This probability threshold was relatively robust for various prevalence and false negative to false positive cost ratios. The prediction accuracy of this model was moderate at the individual level, but is helpful in calves with a reasonable suspicion of being less than 9 d old.

Association of gamma glutamyl transferase activity with fasting glucose among first degree relatives of type 2 diabetes patients

Association of gamma glutamyl transferase activity with fasting glucose among first degree relatives of type 2 diabetes patients - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.096, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Smoking, alcohol intake, and frailty in older Korean adult men: cross-sectional study with nationwide data.

Smoking and alcohol intake are major causes of negative health outcomes and may be co-inherited traits. However, little is known about the association of frailty with smoking and alcohol intake in older adults. Community-dwelling older men (N = 1426) aged 70-84years were divided into four groups: 1) non-smoking (< 100 cigarettes in life-time) and non-alcohol intake (< one time/month); 2) smoking (≥ 100 cigarettes) and alcohol intake (≥ one time/month); 3) non-smoking with alcohol intake; and 4) smoking and no alcohol intake. Frailty was assessed with a modified version of the Cardiovascular Health Study (CHS) frailty index, the Korean version of the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight (KFRAIL) index, the Korean Frailty Index (KFI), and the Study of Osteoporotic Fracture (SOF) frailty index. Frailty risks were estimated with multiple logistic regression models after adjusting for age, income, education, residence, marital status, hospitalization, physical activity, comorbidities, and levels of vitamin B12, aspartate aminotransferase, and gamma-glutamyl transferase. Frailty differed according to smoking and alcohol status. Frailty in the smoking and non-alcohol-intake group was significantly higher according to the CHS frailty index (Odds ratio = 1.592; 95% confidence interval [CI] 1.032-2.455), KFRAIL (CI 1.613, 1.037-2.509), and KFI (CI 1.869, 1.115-3.131) compared with the non-smoking and alcohol-intake group. However, there was no increased frailty risk in the other study groups. Frailty prevalence differed depending on smoking status and alcohol intake in older Korean men. Therefore, we should adopt a comprehensive approach to understanding frailty in older adults that considers both smoking and alcohol intake.

Cnidoscolus aconitifolius leaf extract exhibits comparable ameliorative potentials with ascorbate in dimethylnitrosamine-induced bone marrow clastogenicity and hepatotoxicity

Summary Cnidoscolus aconitifolius (CA) is an edible perennial shrub with promising medicinal properties. We therefore investigated the ameliorative potentials of CA (400 mg/kg) by comparing with ascorbate (400 mg/kg) in dimethylnitrosamine (DMN)-induced clastogenicity and hepatotoxicity. Hepatotoxicity was assessed by determining the levels of reduced glutathione (GSH) and malondialdehyde (MDA), as well as activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione peroxidase (GPx), while clastogenicity was assessed by scoring the number of bone marrow micronucleated polychromatic erythrocytes (mPCEs). Gas Chromatography Mass Spectrophotometry (GCMS) analysis of the CA extract revealed the presence of phenols, essential fatty acid, carotene, and silicon-rich compounds, and also possesses strong in vitro free radical scavenging potentials comparable to ascorbate. DMN-induced hepatic damage as marked by elevated levels of MDA and GSH, as well as activities of ALT, AST, GGT, and GST were significantly reduced by CA and ascorbate treatments, while the significant reductions in CAT, SOD, and GPx activities as a result of DMN administration were restored following treatments with CA and ascorbate. Also, significant increase in DMN-induced micronuclei formation was significantly reduced following CA and ascorbate treatments. Hepatocyte histopathology revealed severe diffuse centrilobular necrosis and bizarre mitotic figures, which were corrected by CA and ascorbate treatments. Overall, ascorbate demonstrates better effect in vitro, while in in vivo study, CA extracts demonstrates a comparable and better ameliorative effects than ascorbate in the parameters investigated. Therapeutic use of the plant may therefore be a promising focus.

Hepatoprotective and immunomodulatory effects of copper-nicotinate complex against fatty liver in rat model.

Aim:The current study was designed to evaluate the potential hepatoprotective and immunomodulatory effects of copper-nicotinate complex (CNC) against methionine- and choline-deficient diet (MCDD)-induced fatty liver in rats.Materials and Methods:Forty male Wistar rats were randomly allocated into one of four equal-sized groups (G1-G4). The G1 group was fed a balanced diet and kept under normal conditions; the G2 group received CNC orally at a dose of 0.043 mg/kg body weight, 3 times/week for 4 weeks, and a balanced diet; the G3 group was fed an MCDD for 4 weeks; and the G4 group was fed an MCDD and administered CNC at the same dose and route as G2. Blood samples were collected for the determination of serum enzyme activity. After 4 weeks of treatment, liver specimens were collected for the evaluation of the oxidative/antioxidative markers, cytokine gene expression, and histopathological examination.Results:CNC improved MCDD-induced liver dysfunctions by recovering serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities to their normal levels. The glutathione (GSH) level and superoxide dismutase (SOD) activity significantly decreased, while lipid peroxidation (as reflected by malondialdehyde [MDA]) markedly increased in the liver tissue of the MCDD group. After cotreatment with MCDD and CNC, the GSH level and SOD activity markedly increased and the MDA level significantly decreased to return to normal levels. After cotreatment with MCDD and CNC, significant downregulation of the mRNA expression of hepatic interleukin (IL)-1β, IL-4, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 genes was found. Moreover, CNC reduced fatty liver complications by reducing the number of hepatic vacuolations, degenerative changes in the hepatocytes, and hemorrhage.Conclusion:CNC has the potential to limit tissue injury and possibly prevent the progression to severe liver disease caused by an MCDD.

Membrane-associated gamma-glutamyl transferase and alkaline phosphatase in the context of concanavalin A- and wheat germ agglutinin-reactive glycans mark seminal prostasome populations from normozoospermic and oligozoospermic men

Background: Human seminal prostasomes are intrinsically heterogeneous extracellular vesicles (EVs) whose composition is, additionally, influenced by different physiological conditions. Aiming at the molecular properties of the prostasomal surface exemplified by glycan compositions as a possible distinction factor, we applied lectin-affinity chromatography (LAC) as a new tool for their separation. Since glycans, generally, exhibit various biological activities, introduction of glyco-parameters as reference could upgrade standardization of EVs isolated by different methods and intended for use in biomedicine.Methods: Preparations of seminal prostasomes from normozoospermic (sPro-N) and oligozoospermic (sPro-O) men were subjected to LAC on concanavalin A (Con A) and wheat germ agglutinin (WGA) columns. Prostasomes recovered in LAC-separated fractions were characterized according to the distribution of selected markers: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), tetraspanin CD63, and total protein/glycoprotein composition.Results: Two CD63-immunoreactive populations exhibiting prostasome signature bands but differing in GGT activity and surface glycans were separated on the WGA column. Additional populations having distinct profiles of total glycoproteins and which can be tracked down by ALP activity were enriched on the Con A column. WGA-separated populations were similar in sPro-N and sPro-O, whereas Con A-separated ones were strikingly different.Conclusions: Membrane-associated gamma-glutamyl transferase and alkaline phosphatase in the context of Con A- and WGA-reactive glycans mark seminal prostasomes populations from normozoospermic and oligozoospermic men.

Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies

Stable and reproducible kidney cellular models could accelerate our understanding of diseases, help therapeutics development, and improve nephrotoxicity screenings. Generation of a reproducible in vitro kidney models has been challenging owing to the cellular heterogeneity and structural complexity of the kidney. We generated mixed immortalized cell lines that stably maintained their characteristic expression of renal epithelial progenitor markers for the different lineages of kidney cellular compartments via the BMP7 signaling pathway from a mouse and a human whole kidney. These cells were used to generate functional and matured kidney spheroids containing multiple renal lineages, such as the proximal tubule, loop of Henle, distal tubules, and podocytes, using extracellular matrix and physiological force, named spheroid-forming unit (SFU). They expressed all apical and basolateral transporters that are important for drug metabolism and displayed key functional aspects of the proximal tubule, including protein endocytosis and increased gamma-glutamyltransferase activity, and cyclic AMP responded to external cues, such as parathyroid hormone. Following exposure, cells fluxed and took up drugs via proximal tubule-specific apical or basolateral transporters, and displayed increased cell death and expression of renal injury marker. Here, we developed a new differentiation method to generate kidney spheroids that structurally recapitulate important features of the kidney effectively and reproducibly using mixed immortalized renal cells, and showed their application for renal toxicity studies.

Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite

BackgroundStudies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and – levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. MethodsPiglets were monitored from birth to 38 days of age (d). The mother sows’ diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows’ diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. ResultsFrom 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. ConclusionsMaternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring’s performance.