Glutamyl Transferase Activity Research Articles

The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

Zafirlukast protects against hepatic ischemia-reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways.

Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its relevant protective mechanism. Thirty-two male Wistar albino rats were randomly allocated to four groups: sham, IRI, ZFK, and ZFK+IR groups. ZFK was administered orally in a dose of 80mg/kg/day for 10 consecutive days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) levels, and gamma glutamyl transferase (GGT) activity were estimated. Liver tissues were used to assess oxidative stress biomarkers including malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx), and reduced glutathione (GSH) contents. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-33 (IL-33), in addition to apoptosis biomarkers, BCL2 associatedXprotein (Bax), B-cell lymphoma 2 (Bcl2) and galactine-9 (GAL9) proteins were also assessed. Western blot analysis was performed for vascular endothelial growth factor (VEGF) and fibrinogen expressions. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and SMAD-4 was done in addition to histopathological examination. Our study revealed that ZFK pre-treatment resulted in liver function restoration and oxidative stress correction. Moreover, inflammatory cytokines were significantly reduced and a remarkable reduction of apoptosis, angiogenesis, and clotting formation has been indicated. Additionally, a significant reduction in SMAD-4 and NF-kB protein expressions was observed. These results were supported by hepatic architecture improvement. Our findings revealed that ZFK possesses a potential protective effect against liver IR possibly through its antioxidant, anti-inflammatory and anti-apoptotic properties.

Evaluation of the Liver Function and Haematological Parameters of Wistar Rats Fed with Casein Protein

Casein is the major protein found in bovine milk. Universally used in human nutrition for all ages and in the dairy industry, milk is regarded as whole food which provides high quality protein and indispensable micronutrients such as vitamins and minerals. The evaluation of the liver function test and haematological parameters of rats fed with casein protein was carried out. Graded levels of casein protein were incorporated into the diets of experimental rats at 20%, 30% and 50% concentrations. At the end of twenty-eight days, blood samples were collected and analyzed for liver function and haematological parameters. Statistically significant increases were observed in lactate dehydrogenase, gamma glutamyl transferase, alanine transaminase, aspartate transaminase and alkaline phosphatase activity levels when compared with the control. Also the granulocytes and platelets counts were significantly reduced. Consistent consumption of high concentrations of casein proteins may elevate liver enzyme activities and attenuate some haematological parameters.

Toxicological assessment of crude oil vapour and the modulating effect of vitamin E on the heart of albino rats

This study investigates the effect of vapour of various concentrations of crude oil and oral co-administration of vitamin E on the heart of albino rats. Thirty (30) albino rats were randomly grouped into six (6) of five (5) rats each and designated A to E. Rats neither exposed to crude oil vapour nor oral administration of vitamin E, rats exposed to oral administration of 15 mg/kg bw vitamin E but not exposed to vapour of crude oil were designated groups A and B. Rats exposed to oral co-administration of vitamin E and vapour of 25%, 50%, 75% and 100% crude oil were designated groups C, D, E and F respectively. Rats’ treatment was over a period of 28 days, after which the rats were euthanized for biochemical analyses. Serum total protein (TP), total cholesterol (CHOL) and triglycerides (TRIG) levels were determined. Standard enzyme assay was conducted for alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transferase and lactate dehydrogenase (LDH) of the heart. Generally, the concentration of TP of serum of other groups of rats, except group B, was significantly higher relative to the Control (p≤0.05). Serum CHOL and TRIG levels increased as the concentration of crude oil increased. Heart AST activities of rats in groups A, B and C were not significantly different (p≤0.05), similarly the AST activities of heart of rats in groups D, E and F were not significantly different (p>0.05). There was no significant difference between the gamma glutamyl transferase (GGT) activity of Control rats not exposed to crude oil vapour and not given oral administration of vitamin E (A) and the Control in Group B (given oral administration of vitamin E but not exposed to crude oil vapour). The specific activity of lactate dehydrogenase (LDH) of heart of both control rats and those of rats exposed to the vapour of various concentrations of crude oil were not significantly different (p>0.05). Experimental evidence from this study revealed that vapour of crude oil can induce biochemical changes in the heart of rats while oral co-administration of vitamin E could reduce the risk posed by exposure to vapour of crude oil by 50%.

Eulophia gracilis pseudobulb extract mitigates cyclophosphamide-induced genotoxicity and oxidative stress on murine hepatic tissue

The reports over the years on chemotherapeutic regimen involving cyclophosphamide (CYP), a bifunctional alkylating agent, demonstrated hepatotoxic side effect. Eulophia gracilis (EG) is a medicinal plant with folkloric utility in the treatment of liver damage and blood related diseases. However, there is a knowledge gap on the impact of E. gracilis effectiveness on CYP-associated hepatic toxicity in the literature. We investigated on potency of aqueous methanolic extract of E. gracilis (AMEG) and CYP-mediated hepatic toxicity in rats. Experimental rats were administered with CYP (2 mg/kg) or co-treated with AMEG (200 or 400 mg/kg) for 7 days consecutively. The result showed that co-treatment with AMEG significantly reduces alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and lactate dehydrogenase activities compared to the CYP group. Moreover, AMEG abated CYP-induced decreases in superoxide dismutase, catalase and glutathione peroxidase enzymes in the liver homogenate. AMEG alleviated CYP-facilitated surges of hepatic concentration of advanced oxidized protein product (AOPPs) and lipid peroxidation in rats. Additionally, AMEG reduced pathological lesions in the liver of co-treated rats and elicited anti-genotoxic effect by mitigating CYP-mediated increases of frequency of formation of polychromatic erythrocyte in the bone marrow and hepatic percentage DNA fragmentation in CYP-exposed rats. Overall, AMEG protective effect improved liver dysfunction occasioned by CYP-mediated toxicities in rats by abating oxidative stress and alleviating genotoxic responses.

Evaluation of gamma glutamyl transferase activity in sera of patients with Alzheimer’s disease

Gamma glutamyl transferase (GGT) plays a role in cellular glutathione uptake, which is an important element of antioxidant mechanisms. An increase in serum GGT is thought to be an early and sensitive marker of oxidative stress. Oxidative stress has a role in the pathogenesis of Alzheimer’s disease (AD). The aim of present study was to investigate the levels of serum Gamma glutamyl transferase (S.GGT) in samples from patient with Alzheimer’s disease.The study included 67 AD patients and 70 individuals as normal controls . Serum Gamma glutamyl transferase GGT and C-reactive protein (CRP) were determined. The study revealed that the S.GGT activity was significantly higher in patients with Alzheimer’s disease (75±2.1IU/L) than in control (healthy individuals) (25±2.1IU/L). The study was carried out in optimum pH (8.2) and optimum temperature 37ć. The results showed that There was a significant positive correlation between age and S.GGT activity in males (r=0.75); and females (r=0.72). Increase in age was significantly associated with raised GGT levels in control group and patients group. The mean serum C-reactive protein (CRP) levels were significantly (p < 0.001) greater in patients group ((33.9 ± 2.3) when compared with control group (4.8±0.2). The high serum GGT concentration may play a critical role in the oxidative stress present in AD brain and, consequently, may play a central role in the pathogenesis of the disease.

Black soldier fly larvae used for environmental enrichment purposes: Can they affect the growth, slaughter performance, and blood chemistry of medium-growing chickens?

This research has been aimed at evaluating the effects of live black soldier fly larvae (BSFL) (Hermetia illucens) on the growth, slaughtering performance, and blood parameters of medium-growing chickens. A total of 240, 28-day-old, Label Rouge Naked Neck chickens were allotted to four experimental groups, according to the gender (males-females) and to the absence (control group, C) or presence (larvae group, L) of a dietary supplementation with 10% live BSFL, on the basis of the expected average daily feed intake (ADFI) (6 replicates/diet, 10 chickens/replicate). The birds were weighed weekly, and the feed consumption was recorded to calculate the average live weight, feed conversion ratio (FCR), average daily gain (ADG), and the ADFI. At 82 days of age, 2 birds/replicate (12 birds/diet) were selected and slaughtered. The blood samples were collected, and the carcass traits (carcass, breast, thigh, and organ weights and yields) were assessed. Overall, the administered live BSFL did not impair the growth and slaughtering performance, or the blood traits, while the C females showed a better FCR than the treated ones (P < 0.05). The live BSFL consumption time was longer for the females than for the males (P < 0.001). The weight of the immune organs (spleen and bursa of Fabricius) increased as the live BSFL supplementation increased (P < 0.05). Furthermore, the provision of live BSFL reduced the gamma glutamyl transferase (GGT, U/l) activity content in the blood (P < 0.05). Finally, both the leukocytes (%) and the monocytes (%) were more abundant in the C groups than in the larvae ones (P < 0.05 and P < 0.01, respectively). In short, the supplementation of live BSFL can be used successfully as an environmental enrichment, without affecting the growth performance of male birds. Furthermore, the immune organ activity could be enhanced by the provision of live BSFL.

Effects of Midazolam on Antioxidant Levels, Biochemical and Metabolic Parameters in Eurygaster integriceps Puton (Hemiptera: Scutelleridae) Eggs Parasitized by Trissolcus semistriatus Nees (Hymenoptera: Scelionidae)

Eurygaster integriceps Puton (Hemiptera: Scutelleridae) is among the most important insect pests of wheat (Triticum sativum L.) and barley (Hordeum vulgare L.) grown in the Middle East. Biological and chemical methods are insufficient to control E. integriceps populations below economic thresholds. In this study, we investigated the effects of midazolam, a clinical drug, on selected metabolic enzyme activity, antioxidant levels, and biochemical parameters in E. integriceps eggs parasitized by Trissolcus semistriatus Nees (Hymenoptera: Scelionidae). Increasing concentrations of midazolam caused cell damage in the parasitized eggs due to its oxidative effects. Transferase enzymes, such as, aspartate transferase, alanine transferase, and gamma glutamyl transferase activities were altered following exposure. Metabolic enzymes, such as, creatine kinase, alkaline phosphatase, amylase, and lactate dehydrogenase also were adversely affected. Levels of the non-enzymatic antioxidants uric acid, bilirubin, and albumin also were altered.

Metabolic Effects of Recombinant Human Growth Hormone Replacement Therapy on Juvenile Patients after Craniopharyngioma Resection.

Objective: To investigate the effect of short-term recombinant human growth hormone (rhGH) replacement therapy on metabolic parameters in juvenile patients following craniopharyngioma (CP) resection. Methods. This retrospective study included 42 cases of juvenile patients that had undergone CP resection in the Department of Endocrinology at the Peking Union Medical College Hospital, from April 2013 to August 2020. According to whether they received growth hormone replacement therapy, the patients were divided into either the growth hormone replacement therapy (GHRT) group (30 cases) or the control group (12 cases). Changes in body mass index (BMI), BMI z-score, transaminase activity, fasting blood glucose (FBG) levels, blood lipid profile, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated after one year of GHRT treatment. Results. The average age of the GHRT group was 13.00 (8.00–14.00) years old and these patients had undergone a CP operation an average of 2.00 (1.62–3.15) years earlier. Prior to receiving GHRT treatment, they received appropriate doses of adrenocortical hormone and thyroid hormone replacement therapy. After one year of GHRT treatment, the average BMI z-score decreased from 1.60 ± 1.76 to 1.13 ± 1.73 (P=0.005). Alanine aminotransferase (ALT) activity decreased from 26.50 (17.00∼98.00) U/L to 18.00 (13.00∼26.48) U/L (P ≤ 0.001), and similar changes were observed with regard to aspartate aminotransferase (AST) and glutamyl transferase (GGT) activity in the GHRT treatment group. The average total cholesterol (TC) decreased from 4.67 (4.10–6.14) mmol/L to 4.32 ± 0.85 mmol/L (P=0.002), and low-density lipoprotein (LDL) levels decreased from 3.05 ± 0.95 mmol/L to 2.56 ± 0.65 mmol/L (P=0.001) in the GHRT treatment group. The average blood urea nitrogen level decreased from 4.53 ± 1.09 mmol/L to 3.92 ± 0.82 mmol/L (P=0.016) and the average serum creatinine (SCr) level decreased from 55.59 ± 12.54 µmol/L to 51.15 ± 10.51 µmol/L (P=0.005) in the GHRT treatment group. The average hsCRP level decreased from 3.23 (1.79∼4.34) mg/L to 0.92 (0.42∼1.21) mg/L in the GHRT treatment group. In the control group, the average ALT activity increased from 26.58 ± 8.75 U/L to 42.58 ± 24.59 U/L (P=0.039), GGT activity increased from 19.0 (13.25–29.25) U/L to 25.00 (14.75–34.75) U/L (P=0.026), and LDL levels increased from 2.27 ± 0.76 mmol/L to 3.43 ± 1.28 mmol/L (P=0.04). Conclusion. GHRT treatment improves the metabolic parameters of juvenile patients that have undergone craniopharyngioma resection by reducing BMI z-scores, low-density lipoprotein, and hsCRP levels and improving liver function.

The relationship between subclinical depressive symptoms and metabolic parameters in women: a subanalysis of the Bialystok PLUS study.

Clinically overt depression is associated with an increased risk for insulin resistance. Data regarding the impact of subclinical depressive symptoms on the risk of diabetes are limited. The study aimed to assess the relationship of subclinical depressive symptoms with body fat distribution and diabetes risk in women. The analysis included 250 women, 68 with subclinical depressive symptoms and 182 controls. A clinical examination, oral glucose tolerance test, and lipid and liver enzyme level assessments were performed. Body composition was estimated by dual‑energy X‑ray absorptiometry. The participants completed the Beck Depression Inventory (BDI) questionnaire. The women with subclinical depressive symptoms had higher visceral adipose tissue (VAT) mass than the control group. The groups did not differ in the body mass index, waist circumference, total fat, fat‑free, android, and gynoid fat mass. Homeostatic Model Assessment for Insulin Resistance (HOMA‑IR) and alanine aminotransferase (ALT) activity were higher in the women with subclinical depressive symptoms than in the control group. In the women with subclinical depressive symptoms, we observed a positive correlation between the severity of somatic‑vegetative symptoms reported in the BDI and VAT mass, HOMA‑IR, and gamma glutamyltransferase (GGT) activity. Dysglycemia occurred more frequently in the women with subclinical depressive symptoms. In a subgroup analysis of postmenopausal women, the individuals with subclinical depressive symptoms had higher HOMA‑IR, GGT, ALT, and triglyceride / high‑density lipoprotein cholesterol ratios than the control group. Subclinical depressive symptoms in women might predispose to dysglycemia.

Acute Syphilitic Hepatitis in the Early Secondary Phase: A Case Report and Literature Review

Background: The incidence of syphilis is clearly increasing. It is a source of visceral damage, particularly in the secondary phase. Acute syphilitic hepatitis is a rare clinical entity classically described but under-diagnosed because of its non-specific presentation. Case Presentation: We report the case of a 25-year-old French woman, without comorbidity, sexually active, having unprotected sex with only one partner. She was admitted to our unit for jaundice and a disturbed liver function test preceded 3 weeks earlier by a rash. The patient did not consume alcohol and did not report the introduction of a new medication. A skin rash compatible with syphilitic roseola and generalized adenopathy were found. The liver workup showed alanine aminotransferase (ALT) at 1984 U/L, aspartate aminotransferase (AST) at 1377 U/L, total bilirubin at 221 μmol/L, alkaline phosphatase activity (APL) at 419 U/L, gamma glutamyl transferase activity (GGT) at 229 U/L and a prothrombin concentration at 73%. The search for the most common etiologies of acute hepatitis was negative. Syphilitic serology was positive with a Treponema Pallidum Hemagglutinations Assay (TPHA) titration of 5120 IU and Veneral Disease Research Laboratory (VDRL) of 64 IU. Abdominal ultrasound revealed only homogeneous hepatomegaly and splenomegaly with no focal lesions. Other sexually transmitted infections (STI) were negative and her partner had positive syphilis serology. After a single dose of Benzathine benzylpenicillin, the clinical signs regressed after one week and the hepatic balance tended to normalize 20 days later. Conclusion: This highlights the need for a high index of suspicion for syphilitic hepatitis in sexually active patients presenting with acute hepatitis associated with a cutaneous rash.

Determination of the Gamma Glutamyl Transferase (GGT) Activity in Gestational Diabetes

Determination of the Gamma Glutamyl Transferase (GGT) Activity in Gestational Diabetes

Pattern of Alpha Fetoprotein and Activities of Liver Enzymes in Type 2 Diabetic Patients Attending Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which has become health problem of global interest, linked to renal disease. The study is to assess the activities of some liver enzymes and alpha fetoprotein level in type 2 diabetic patients. 81 participants comprised 38 diabetics and 43 controls were randomly recruited. Informed, oral and written consent was obtained from the participants. Ethical approval was obtained. 6mls of fasting blood samples were collected. Plasma glucose, alpha feto-protein (AFP) levels; serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) activities were analyzed using standard laboratory methods. The results showed significantly increased plasma glucose level in the diabetics than in controls (p=0.000), as well as in male diabetics than in female diabetics (p=0.048). But, the mean age, AFP, ALT, AST, ALP and GGT activities were the same in the diabetics and the controls; and in male and female diabetics at p&gt;0.05 in each case. Relatively strong positive significant correlation was observed between ALT Vs AST (r=0.566; p=0.000) and a weaker negative association exist between ALT Vs Age (r= -0.353; p=0.022) in diabetics but no associations were observed with other parameters studied. In conclusion the positive association between ALT and AST may reveal transaminase derangements in liver status of type 2 diabetic subjects studied.

The role of resveratrol in hepatotoxicity caused by methotrexate

Methotrexate is an immunosuppressive and antineoplastic drug that may induce hepatotoxicity. Resveratrol is a compound that has a protective effect thanks to its antioxidant role. In present study was aimed to investigate posibble protective effects of resveratrol in methotrexate induced hepatotoxicity. Eighteen Wistar Albino rats were equally divided into three groups: Control, Methotrexate, Methotrexate + Resveratrol. After a single dose of methotrexate (15 mg/kg, i.p.), resveratrol (10 mg/kg, orally) was applied for 7 days. Fallowing 7 days, rats were sacrificed. Histopathological (H-E staining), immunohistochemical (Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa) and biochemical (Total Oxidant Status, Total antioxidants Status and Oxidative Stress Index) analyses were assayed in liver tissue samples. Additionally, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin activities were assayed in serum samples for biochemical analyses. Normal liver tissues were observed in control groups. Histopatholocigal changes, high staining of Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa, increasing levels of tissue Total Oxidant Status, Oxidative Stress Index and decreasing levels of tissue Total antioxidants Status were observed in methotrexate groups. Moreover, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin levels increased in methotrexate groups too (p&amp;lt;0.05). However, these findings were lower in the Methotrexate + Resveratrol groups (p&amp;lt;0.05). In this study were observed that oxidant levels could increase after methotrexate applied in the liver, whereas resveratrol alleviated effects of hepatotoxicity by histopathological, immunohistochemical and biochemical analyses. However, molecular studies are needed to clearly understand mechanism of resveratrol.

Gamma Glutamyl Transferase Activity Has Limited Utility in Assessment of Alkaline Phosphatase Elevations.

As part of an ongoing effort to improve healthcare value for patients, laboratories increasingly implement test utilization review. Alkaline phosphatase (ALP) isoenzymes (hereafter: isoenzymes) testing distinguishes the various ALP isoforms to explain elevations in total serum ALP. Gamma glutamyl transferase activity (GGT) has served as a proxy for total ALP elevations attributable to the hepatic isoform given that both are membrane-bound proteins with a shared mechanism of release. We assessed the utility of GGT in evaluating isoenzymes requests. We obtained 8 years of isoenzymes results and identified same-patient GGT measurements obtained within 7 days. We assessed the ability of GGT to predict elevations in hepatic, bone, intestinal, and nonhepatic ALP isoforms overall. We generated ROC curves and calculated sensitivity and specificity using our in-house reference limits for GGT. GGT as a predictor of hepatic isoform elevation had an area under the ROC curve (AUC) of 0.68, and GGT activity above the upper reference limit was 46.6% sensitive and 85.0% specific for hepatic ALP elevation. GGT activity as a predictor of nonhepatic isoform elevation had an AUC of 0.52, and GGT within reference limits was 59.8% sensitive and 46.4% specific for elevation in a nonhepatic ALP isoform. In 133 individuals with hepatic isoform elevations, 93 had a concurrent elevation in a nonhepatic ALP isoform. GGT was reasonably specific but insensitive for hepatic ALP isoform elevation and was a poor predictor of ALP isoform elevation overall, suggesting that its usefulness in evaluating isoenzymes orders is limited.

High glucose-induced Smad3 linker phosphorylation and CCN2 expression are inhibited by dapagliflozin in a diabetic tubule epithelial cell model.

Background: In the kidney glucose is freely filtered by the glomerulus and, mainly, reabsorbed by sodium glucose cotransporter 2 (SGLT2) expressed in the early proximal tubule. Human proximal tubule epithelial cells (PTECs) undergo pathological and fibrotic changes seen in diabetic kidney disease (DKD) in response to elevated glucose. We developed a specific in vitro model of DKD using primary human PTECs with exposure to high D-glucose and TGF-β1 and propose a role for SGLT2 inhibition in regulating fibrosis. Methods: Western blotting was performed to detect cellular and secreted proteins as well as phosphorylated intracellular signalling proteins. qPCR was used to detect CCN2 RNA. Gamma glutamyl transferase (GT) activity staining was performed to confirm PTEC phenotype. SGLT2 and ERK inhibition on high D-glucose, 25 mM, and TGF-β1, 0.75 ng/ml, treated cells was explored using dapagliflozin and U0126, respectively. Results: Only the combination of high D-glucose and TGF-β1 treatment significantly up-regulated CCN2 RNA and protein expression. This increase was significantly ameliorated by dapagliflozin. High D-glucose treatment raised phospho ERK which was also inhibited by dapagliflozin. TGF-β1 increased cellular phospho SSXS Smad3 serine 423 and 425, with and without high D-glucose. Glucose alone had no effect. Smad3 serine 204 phosphorylation was significantly raised by a combination of high D-glucose+TGF-β1; this rise was significantly reduced by both SGLT2 and MEK inhibition. Conclusions: We show that high D-glucose and TGF-β1 are both required for CCN2 expression. This treatment also caused Smad3 linker region phosphorylation. Both outcomes were inhibited by dapagliflozin. We have identified a novel SGLT2 -ERK mediated promotion of TGF-β1/Smad3 signalling inducing a pro-fibrotic growth factor secretion. Our data evince support for substantial renoprotective benefits of SGLT2 inhibition in the diabetic kidney.

English

BACKGROUND Alcoholism remains to be the major cause of morbidity and mortality throughout the world. Consuming alcohol is the potent etiological factor for the development of alcoholic liver diseases (ALD), ranging from fatty liver to hepatocellular carcinoma with varying rates of development in both genders depending on the quality, quantity, and duration of the drink. Zinc deficiency has been documented with the progression of alcoholic liver disease. It is also a well-known fact that zinc is a co-factor for enzyme alkaline phosphatase. This study aims to assess the zinc status and alkaline phosphatase activity in patients with various stages of alcoholic liver disease, correlate zinc with alkaline phosphatase activity, albumin, gamma glutamyl transferase activity, MELD score and duration of alcohol intake and analysing the need for evaluating zinc in these patients. METHODS This comparative observational study involves group I healthy controls and group II patients diagnosed to have ethanol related decompensated liver disease with or without portal hypertension for more than three years from the Department of Medical Gastroenterology, Government Medical College Hospital. 5 ml of venous blood in fasting state was collected from both groups and assayed for serum zinc, and serum alkaline phosphatase activity. The data was statistically analysed. RESULTS The study results demonstrate that higher percentage of patients with alcoholic liver disease have low serum zinc levels than healthy controls. Zinc when compared with variables like serum albumin, duration of alcohol intake, MELD score, serum gamma glutamyl transferase and alkaline phosphatase in the case and control groups were found to be statistically significant. CONCLUSIONS There is decrease in serum zinc level and increased alkaline phosphatase activity in patients with alcoholic liver disease. The statistically significant data is a strong rationale for evaluating the zinc status and thereby supplementing zinc to patients with alcoholic liver disease. KEYWORDS Alcoholic Liver Disease, Zinc, Alkaline Phosphatase, MELD Score

Preservation of antioxidant defense system by Morin in bicalutamide-induced rat testicular toxicity

Bicalutamide (BCT) is a potent anti-androgen chemotherapeutic drug indicated for prostate cancer. However, BCT is known to cause oxidative stress and impairment of male reproductive function. Whereas Morin (MOR), a flavonoid has been found to be a potent antioxidant, with free radical scavenging capacity. This study investigated the protective effect of MOR on BCT-induced testicular toxicity in Wistar rats. Twenty-four male albino rats were randomized into four groups (n=6/group). Group I which served as control received distilled water. Group II, received 3 mg/kg body weight (bwt) BCT orally (per os); group III received 3 mg/kg/day BCT p.o. plus 100 mg/kg/d MOR p.o. and group IV received 100 mg/kg/d MOR p.o. All treatments lasted for 14 days, thereafter, animals were sacrificed and epididymis and testis were collected for sperm and biochemical analyses. The result revealed that BCT treatment caused a significant increase in abnormal sperm morphology. Sperm production, sperm count, motility and viability were significantly reduced when compared with control (p&lt;0.05). Similarly, testicular superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),glutathione S-transferase (GST) and acid phosphatase (ACP) activities, as well as ascorbic acid and GSH levels were significantly reduced in the BCT- treated animals when compared to control (p&lt;0.05). Conversely, testicular alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenese (LDH) activities as well as malondialdehyde (MDA) levels of BCT-treated animals increased significantly relative to control (p&lt;0.05). However, co-treatment with Morin ameliorated BCT-induced alterations in sperm parameters, ascorbic acid, GSH and MDA levels, as well as LDH, SOD, CAT, GST, GPX, ACP, ALP and GGT activities. Data obtained from this study suggest that Morin protected against altered sperm parameters and testicular oxidative stress caused by BCT.&#x0D; Keywords: Bicalutamide, Anti-androgen, Testis, Oxidative stress, Morin, Antioxidant, Rat

Pathophysiological effects of Klebsiella pneumoniae infection on Galleria mellonella as an invertebrate model organism.

Klebsiella pneumoniae is an important human pathogen causing urinary tract infections and pneumonia. Due to the increase in resistant strains and being an opportunistic pathogen, it is very important to determine the virulence process, the cellular damage it causes in the host and the immunological response level of the host. In this study, invertebrate infection model Galleria mellonella larvae were used to investigate cellular damage, antioxidant response and changes in biochemical parameters due to K. pneumoniae infection. The activity of cell damage indicators alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase increased in hemolymph of G. mellonella larvae due to K. pneumoniae virulence. Creatine kinase, alkaline phosphatase, gamma glutamyl transferase and amylase activities were increased to regulate the disrupted energy metabolism due to infection. As a result of the damage caused by K. pneumoniae infection, changes occurred in the amount of non-enzymatic antioxidants, uric acid, bilirubin and albumin. Due to K. pneumoniae infection, the amount of calcium, potassium, magnesium and phosphorus altered. This study showed that G. mellonella larvae was important infection model in the investigation of infectious cell damage and physiological effects, given the opportunistic nature of the K. pneumoniae pathogen and the lack of adequate animal models.

EquineReview

Introduction: Peritonitis in horses, equine bleeding and the pathogenesis of gamma glutamyl-transferase activity in Thoroughbred horses are discussed in this month's selection of three recent papers for equine practitioners.