Γ-glutamyltransferase Activity Research Articles

Characterizing physiological status in three breeds of bulls reared under ecological and climate conditions of the Altai region

Ecological and climatic factors have an impact on the health, productivity and reproduction of the cattle. The goal of this work is the study of physiological status of servicing bulls reared under ecological and climate conditions of the Altai region, by defining the differences between Red-Steppe, Simmental and Black-and-White breeds in spermatogenic, hormonal, biochemical and hematological parameters. Samples of peripheral blood and ejaculates were taken from 48 grown-up servicing bulls (average age 5.6±0.3 years) in autumn period. It was established that Red-Steppe bulls have higher concentrations of nonorganic phosphorus, leucocytes, erythrocytes, hemoglobin, hematocrit and erythrocyte sedimentation rate in comparison with animals of Simmental breed, and the hemoglobin concentration and hematocrit are also higher in comparison with Black-and-White breed. It was noted that bulls of Black-and-White breed have a higher level of cortisol in comparison with the other breeds. The lowest level of serum urea and total protein and increased serum activity of creatine kinase and γ-glutamyl transferase, as well as the heaviest body weight were observed in Simmental breed bulls. The differences between breeds in a wide spectrum of physiological measures reflect not only genetically determined peculiarities of homeostatic mechanism, but also may reflect different ability to adapt to local ecological and climate conditions of the Altai region. Spermatogenic, biochemical and hematological measures in bull sires reared in the Altai region were similar to those in bulls bred in other Russian regions and some other countries. The measures reported could serve as reference values and therefore represent ‘normal’ values of physiological status for these bull sires reared in this ecological and climatic zone, but could be utilized in further studies for comprehensive monitoring of cattle breeding stock in other ecological and climatic zones of the Siberian region of Russia.

Endoscopic nasobiliary drainage: an effective treatment option for benign recurrent intrahepatic cholestasis (BRIC)

Benign recurrent intrahepatic cholestasis (BRIC) is characterised by recurrent episodes of jaundice, severe pruritus and low or normal serum γ-glutamyltransferase activity lasting from several weeks to months. BRIC is an...

Safety assessment of the aqueous extract of the flowers of Nymphaea lotus Linn (Nymphaeaceae): Acute, neuro- and subchronic oral toxicity studies in albinos Wistar rats.

Background Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system. Methods Aqueous extract of N. lotus at doses of 200, 400 and 600 mg/kg body weight (BW) was evaluated for nitrites contents and orally administered to rats daily for 28 days (5 male, 5 female per group). The control group received distilled water (10 mL/kg) and a satellite group was used to observe reversal effects. Neurotoxicity of the plant was determined using open field test for motor coordination, ataxia and gait analysis. Clinical signs and state of livelihood were recorded during the 24 h, then for 28 days of treatments. At the end of 28-day period, animals were anesthetized and decapitated. The whole brain was homogenized for neurobiochemical analysis. Blood samples were collected with or without anticoagulant for hematological examinations and serum analysis. Specimens of liver, kidney, testis, ovaries, and brain were fixed in 10 % formalin and processed for histopathological examinations. Results Our findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract of N. lotus. Acute toxicity study revealed no signs of toxicity neither at the dose 2,000 mg/kg nor at 5,000 mg/kg. Thus the LD50 value of aqueous extract of N. lotus flowers is superior to 5,000 mg/kg. The repeated administration of N. lotus during 28 days, induced no signs of neurobehavioral changes in male, but female rats exhibited dose-dependent response in the open field test, suggesting sex and dose-relative psychotropic effects of N. lotus. The evaluation of neurobiochemistry revealed consistent rise of brain cholesterol by 44.05 %; 158.10 % and 147.62 % respectively in male rats treated with the doses of 200, 400 and 600 mg/kg. In female rats, these levels were significantly increased (p<0.001) only at the dose of 600 mg/kg compared to control. This trend persisted after 14 days withdrawal. Brain potassium and calcium concentrations were increased in all rats compared to their respective control receiving distilled water, suggesting transmembrane current stabilizing properties of brain cells by our extract. Further, serum biochemical analysis demonstrated that 28-day administration of N. lotus flowers increased depending on the dose and sex, the levels of serum urea, proteins, creatinine and bilirubin and reduced γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities. These results suggest liver alterations that are endowed by lower liver relative weight and histology damages observed in female rats treated with the dose of 600 mg/kg of our extract. We also observed a rise in the low-density lipoprotein (LDL) fraction and AI of male rats undergoing N. lotus treatment. In female rats, the latter remains unaltered, confirming the dose- and sex-dependent response of our extract. The levels of white blood cells (WBC) and granulocytes were higher in male irrespective to their control, revealing stimulatory properties of the male hematopoietic system. Such variations (sex- and dose-dependent) are without biological relevance for the majority of the biochemical parameters evaluated, indicating a wide margin of safety for the traditional use of N. lotus. The alkaloids, nitrites and phytosterols contained in N. lotus flowers extract may probably account for its neuroprotective, anti-oxidant, and immunoboosting properties. Conclusions N. lotus do not possesses neurotoxicity but is able to induce behavioral changes in rats. Therefore, the application of this plant as either drug or supplementary food should be carefully considered.

Protective effect of Moringa oleifera oil against HgCl2-induced hepato- and nephro-toxicity in rats

Various parts of the Moringa oleifera (M. oleifera) tree are widely accepted to have ameliorative effects against metal toxicity. In the present study, M. oleifeira oil (MO) was tested against HgCl2-induced tissue pathologies and oxidative stress. Male Wistar rats were administered MO (1.798 mg/kg p.o.) or HgCl2 (5 mg/kg body wt) alone or in combination (5 mg/kg HgCl2+1.798 mg/kg MO p.o.) three times per week for 21 days. After exposure and treatment periods, rats were sacrificed; blood collected and the oxidative status of the liver and kidney homogenates were evaluated. In the liver, malondialdehyde (MDA) level, glutathione (GSH), and superoxide dismutase (SOD) activities were higher whereas catalase (CAT) activity was lower in the HgCl2 group than in the control group. In the kidney, MDA level, SOD, and CAT activities were higher whereas GSH activity was unchanged in the HgCl2 group compared to the control group. In the liver, MDA level, SOD, and CAT activities were lower in the HgCl2+MO group than in the HgCl2 group. In the kidney, MDA level, SOD and CAT activities were lower in the HgCl2+MO than in the HgCl2 group. Furthermore, Hg-induced increases in creatinine and bilirubin levels as well as the increase in γ-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase activities were attenuated in the combine exposure group and the animals showed improvement in the histology of the liver and kidney. MO decreased the negative effects of Hg-induced oxidative stress in rats.

Influence of γ-glutamyltransferase and alkaline phosphatase activity on in vitro fertilisation of bovine frozen/thawed semen

The aim of this work was to evaluate whether the residual amount of γ-glutamyl-transferase (GGT) and alkaline phosphatase (ALP) in bovine sperm after freezing/thawing is correlated with fertility parameters, including blastocyst rates after in vitro fertilisation (IVF). The enzyme activities were determined in both spermatozoa and supernatant after centrifugation. While ALP was only correlated with sperm viability, GGT activity was correlated with sperm motility (rs = .4; p < .05) both in sperm and supernatant. Interestingly, GGT activity was also correlated with cleavage (rs = .5; p < .05 and .8; p < .01, for sperm and supernatant respectively) and blastocyst (rs = .6 and .9, for sperm and supernatant respectively; p < .01) rates obtained after IVF. These results suggest that GGT could play an important role in the protection of sperm against oxidative stress and could be considered a reliable marker to assess frozen/thawed sperm quality in bovine.

Improved production of poly-γ-glutamic acid with low molecular weight under high ferric ion concentration stress in Bacillus licheniformis ATCC 9945a

This study found that high ferric ion (Fe3+) concentrations lead to high poly-γ-glutamic acid (γ-PGA) production and low-molecular-weight γ-PGA. In cultures containing 7.4 mmol/L FeCl3, the average molecular weight of γ-PGA reached 3.18 ± 0.3 × 105 Da, which is a 76% decrease from that in the culture without FeCl3 (1.31 ± 0.14 × 106 Da). Cultures containing increasing concentrations of FeCl3 (0–7.4 mmol/L) showed a corresponding increase in γ-PGA yield from 26.57 ± 1.64 to 34.93 ± 1.05 g/L. Transcription level analysis indicated that high FeCl3 concentrations could enhance the expression of γ-PGA synthetase genes (pgsA, pgsB, and pgsC), which may contribute to the improved production of γ-PGA. In addition, γ-PGA degradation genes ggt (encoding γ-glutamyltransferase) and cwlO were found to contribute to a lower γ-PGA molecular weight in cultures containing 7.4 mmol/L FeCl3. The result of γ-glutamyltransferase activity was in agreement with the results of the transcription level analysis. Overall, this study would provide a novel method for the regulation of synthesis of γ-PGA with low molecular weight.

Resveratrol alleviates ethanol-induced hormonal and metabolic disturbances in the rat.

Resveratrol is a polyphenol found in different plant species and having numerous health-promoting properties in animals and humans. However, its protective action against deleterious effects of ethanol is poorly elucidated. In the present study, the influence of resveratrol (10 mg/kg/day) on some hormones and metabolic parameters was determined in rats ingesting 10 % ethanol solution for two weeks. Blood levels of insulin, glucagon and adiponectin were affected by ethanol, however, resveratrol partially ameliorated these changes. Moreover, in ethanol drinking rats, liver lipid accumulation was increased, whereas resveratrol was capable of reducing liver lipid content, probably due to decrease in fatty acid synthesis. Resveratrol decreased also blood levels of triglycerides and free fatty acids and reduced gamma-glutamyl transferase activity in animals ingesting ethanol. These results show that resveratrol, already at low dose, alleviates hormonal and metabolic changes induced by ethanol in the rat and may be useful in preventing and treating some consequences of alcohol consumption.

Relation of serum γ-glutamyl transferase activity with copper in an adult population

The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, p<0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, p<0.001; r=0.230, p=0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol

Context: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials.Objective: This study was designed to evaluate the protective effects of RUT against cadmium (Cd) + ethanol (EtOH)-induced hepatic and renal toxicity in rats.Materials and methods: Wistar rats were treated with Cd (50 mg/kg) alone or in combination with EtOH (5 mg/kg) and RUT (25, 50 and 100 mg/kg) for 15 days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods.Results: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd + EtOH group and lowest in Cd + EtOH animals co-treated with the highest dose of RUT (2.98 ± 0.34, 10.08 ± 2.32, 4.99 ± 1.21 vs. 1.69 ± 0.33, 6.13 ± 0.28, 3.66 ± 1.12 μmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd + EtOH treated animals compared to Cd + EtOH animals co-treated with 100 mg/kg RUT (2.54 ± 0.08 vs. 1.28 ± 0.04 ppm). Furthermore, RUT at the highest dose protected against Cd + EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86 ± 2.74 vs. 122.52 ± 6.35 µmol/L; 1.77 ± 0.35 vs. 3.23 ± 0.55 mmol/L; 9.56 ± 1.22 vs. 16.21 ± 1.64 U/L; 288.92 ± 40.12 vs. 159.8 ± 18.01 U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd + EtOH animals co-treated with RUT in a dose-dependent manner.Discussion and conclusion: RUT protected against the combined effects of Cd + EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood.

Effect of Fasting on Enzymes of Carbohydrate Metabolism, Brush Border Membrane and on Transport Functions in Superficial and Juxta-Medullary Cortex of Rat Kidney

The effect of 1, 3 and 5-day fasting was studied on serum parameters; enzymes of brush border membrane and carbohydrate metabolism; transport of Pi and proline in different parts of the rat kidney. Fasting decreased the activities of lactate dehydrogenase, malate dehydrogenase but increased the activities of glucose-6-phosphatase and fructose 1,6-bisphosphatase; glucose-6-phosphate dehydrogenase and malic enzyme. These observations suggest that the degradation of glucose is decreased but its production by gluconeogenesis is enhanced upon fasting. Fasting led to significant decrease in the specific activities of Brush Border Membrane (BBM) enzymes, alkaline phosphatase and γ-glutamyl transferase in BBM vesicles prepared from superficial and juxta-medullary cortex. The transport of Pi was also decreased albeit differentially in these BBM preparations. Kinetic studies revealed that the activity of BBM enzymes and Pi transport decreased due to changes in Vmax and Km values. The results show that fasting caused significant decrease in metabolic enzymes involved in energy generation that led to decreased transport functions of the kidney.

Sublethal toxicity of TiO2 nanoparticles to common carp (Cyprinus carpio, Linnaeus, 1758) under visible light and dark conditions

The objective of this study was to determine the sublethal toxicity of TiO 2 nanoparticles (TiO 2 -NPs) on common carp ( Cyprinus carpio ) under visible light and dark conditions. Blood sampled was collected after 21 days and biochemical parameters, including glucose, total protein, albumin, globulin, creatinine, triglyceride and cholesterol levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK), and alkaline phosphatase (ALP) activities were measured. The results showed that TiO 2 -NPs is caused a significant effect on blood biochemical parameters of C. carpio . By changing lighting conditions from darkness to light, significant differences were observed in certain blood biochemical parameters, including AST, ALT, LDH, ALP and CK activities, glucose, cholesterol and triglyceride levels in fish exposed to TiO 2 -NPs under light conditions as compared with fish exposed to TiO 2 -NPs under dark conditions. Cholesterol and triglyceride levels in fish exposed to 0.0 mg L -1 TiO 2 -NPs under darkness conditions were significantly higher than the control. The results revealed that toxicity of TiO 2 -NPs under visible light conditions was more than darkness conditions.

Efficacy and Safety of the Use of Baclofen in the Treatment of Alcohol Dependent (a Double-Blind, Randomized, Placebo-Controlled Pilot Study)

Objective. To study the efficacy and use of baclofen (Baclosan) for stabilizing remission in patients with alcoholism. Materials and methods. A total of 32 patients with alcoholism were randomized to two groups. Patients of group 1 (16 patients) received baclofen (50 mg/day) for three months; patients of group 2 received a placebo of identical appearance. All patients were required to attend the clinic every week for monitoring of remission (alcohol consumption) and assessment of the levels of alcohol attraction (craving), affective disorders (depression and anxiety), and γ-glutamyltransferase (GGT) activity, and for monitoring of compliance with medication (urine riboflavin). Alcohol consumption was monitored by retrospective analysis and assay of GGT. Anxiety was evaluated using the Hamilton and Spielberger scales. Depression was assessed on the Montgomery-Asberg Depression Scale. Alcohol cravings were assessed using obsessive-compulsive, Pennsylvania, and visual analog scales. Overall assessment of treatment efficacy was obtained using the Clinical Global Impression scale. The study followed a double-blind design. Results and conclusions. No significant difference in measures of the efficacy of stabilizing remission was seen between the baclofen and placebo groups in patients with alcoholism (probably due to insufficiently large cohort sizes). Measures of holding patients in remission and of alcohol consumption in the baclofen group were somewhat better than in the placebo group; between-group differences in these measures approached statistical significance, pointing to a greater efficacy for baclofen than placebo in alcoholism. Baclofen did not show any significant difference from placebo in terms of the number of side effects (adverse events) and effects on liver enzyme activity, which is evidence for its good tolerance and safety in this contingent of patients. The authors take the view that evidence-based conclusions regarding The efficacy of baclofen in the treatment of alcoholism require further studies in patients using larger cohorts.

Effects of micro-plastic particles on paraquat toxicity to common carp (Cyprinus carpio): biochemical changes

In this study, we investigated the possible effects of paraquat and micro-plastics on blood biochemical parameters in common carp (Cyprinus carpio). We exposed C. carpio for 21 days to sublethal concentrations of paraquat (0.2 and 0.4 mg L−1) and micro-plastics (1 and 2 mg L−1), alone or in combination. Blood biochemical analysis indicated that exposure to 0.4 mg L−1 paraquat and mixture of paraquat and micro-plastics was followed by an increase in aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatine phosphokinase (CPK) activities and glucose levels. The activity of ALP and CPK showed a significant increase in fish treated with 2 mg L−1 micro-plastics. No significant changes were observed in glucose level, AST, ALT, and LDH activities in fish exposed to micro-plastics. Exposure to paraquat and/or micro-plastics resulted in a significant decrease in total protein, globulin, cholesterol, and triglyceride levels and γ-glutamyl transferase activity. When fish were exposed to paraquat or paraquat and micro-plastics, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities increased significantly compared to the control group. Treating fishes with a mixture of paraquat and 2 mg L−1 micro-plastics caused a significant increase in albumin levels. However, a significant decrease in the albumin level was observed after exposure to paraquat or micro-plastics. Creatinine levels increased after exposure to paraquat and/or micro-plastics. The results indicate that increased doses of micro-plastics in water significantly increased toxic effects of paraquat in fish. Finally, these data support the hypothesis that changes in blood biochemical parameters were induced by exposure to paraquat and/or micro-plastics.

Effect of Ethanolic Extract from Seeds or Pods of Xylopia Aethiopica (Dunal) A. Rich (Annonaceae) on the Testicular Function of Adult Male Rats.

Xylopia aethiopica (Annonaceae) is used in some folk medicines and widely consumed as a spice in some parts of Nigeria. Its efficacy as an anti-androgenic substance has warranted the attention of African scholars. This study evaluated the enzymatic activity of lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT), sperm quality (motility, count, morphology), testosterone level and histo-pathological changes of the testis of rats chronically treated with ethanolic extract of the pods (without seeds), seeds, and fruits (pods+seeds) of Xylopia aethiopica. Male Wistar (224-246g) rats were treated with the extract of the pods, seeds, and fruits of Xylopia aethiopica at the dose of 0, 50, 100, and 200mg/kg body wt. for 60days. Serum biochemistry, sperm quality and histo-pathological examination of the testis were assessed for any treatment-related adverse effects. After treatment with Xylopia aethiopica, testosterone level was decreased dose-dependently in the animals treated with the seed extract compared to all other groups. The enzymatic activities of LDH and γ-GT were higher in rats treated with the seed and fruit extracts compared with those treated with the pods. The numbers of motile sperm, and counts were decreased while the numbers of sperm with morphological defects were higher in rats treated with the seed and fruit extracts compared to the control. Histopathological changes of the testis were also more severe in rats treated with the highest dose of the seed extract. We conclude that the compounds related to the anti-infertility effects of Xylopia aethiopica are present in the seeds.

Antioxidant protection and lipid peroxidation in testes and different parts of epididymis in boars

The antioxidative ability of testes and epididymis to protect spermatozoa from detrimental effects of oxidation processes induced by excessive generation of reactive oxygen species has not been previously studied in detail in boar reproductive tissues. The aim of this study was to investigate differences in level of antioxidative protection, intensity of lipid peroxidation, and values of biochemical parameters in testes and different parts of epididymis in sexually mature boars. The study was performed on five Swedish landrace boars from the same litter aged 10 months kept under same ambient conditions. After slaughtering performed at the end of November; tissue samples of testes and the head, body and tail of epididymis were taken. The activity of glutathione peroxidase, glutathione reductase, superoxide dismutase, γ-glutamyltransferase, acid phosphatase, and lactate dehydrogenase, and concentrations of triacylglycerol, phospholipids, cholesterol, free fatty acids were determined in obtained supernatants from homogenized tissues spectrophotometrically; the concentration of malondialdehyde was determined by high-performance liquid chromatography. Significantly higher activities of glutathione peroxidase and glutathione reductase (P < 0.05) were found in testes compared with epididymis. In testes, a significantly higher activity of superoxide dismutase was found than in the head and tail of epididymis (P < 0.05). Malondialdehyde concentration in head of epididymis was significantly higher than in testes, or the body and tail of epididymis (P < 0.05). Simultaneously, malondialdehyde concentration in testes was significantly higher than in body and tail of epididymis (P < 0.05). In tail of epididymis, significantly higher activities of γ-glutamyltransferase, acid phosphatase, and lactate dehydrogenase were recorded than in testes. Significantly lower concentrations of triacylglycerol and free fatty acids were recorded in epididymis tail in comparison to epididymis head (P < 0.05). It could be concluded that high activities of antioxidative enzymes in testes of boars are essential for the appropriate protection of spermatozoa and cells of testes tissue against oxidative damages. The tissues of testes and epididymis head in boars were more susceptible to lipid peroxidation. Results of the present study indicated physiological importance of antioxidative enzymes in reproductive system in boars, and thus may serve for better understanding the mechanisms of male infertility.

Utility of γ-Glutamyl Transferase in Predicting Troponin Elevation in Emergency Departments.

Serum γ-glutamyl transferase (GGT) activity is a risk predictor for the development of coronary artery disease and is related to cardiovascular morbidity and mortality. We evaluated the clinical utility of GGT activity in predicting high troponin levels in patients with acute coronary syndrome (ACS) admitted to the emergency department with chest pain. A total of 200 troponin-positive and 203 troponin-negative patients were classified into groups 1 and 2, respectively. γ-Glutamyl transferase activity was significantly higher in group 1 (44 ± 34 U/L) compared with group 2 (31 ± 26 U/L, P = .001). A GGT activity cutoff >25.5 showed 62% sensitivity and 61% specificity in predicting troponin positivity. Logistic regression analysis demonstrated a significant predictive value of GGT for troponin positivity. Spearman rank correlation analysis showed a moderately strong relationship between GGT activity and troponin positivity. Considering the predictive value of high GGT activity for troponin positivity, GGT activity may complement other diagnostic biomarkers for predicting troponin positivity in patients having ACS admitted with chest pain.

Fluazifop- p-butyl, an aryloxyphenoxypropionate herbicide, diminishes renal and hepatic functions and triggers testicular oxidative stress in orally exposed rats.

Fluazifop- p-butyl (FPB) is a selective aryloxyphenoxypropionate herbicide. Its phytotoxicity mechanism involves inhibition of lipid biosynthesis, free-radical generation, and oxidative stress in vulnerable plants. This study evaluates the impact of orally administered FPB on selected tissues in non-target animal model. Twenty-four male wistar rats (160-180g) were randomized into groups (I-IV). Group-I served as control, while animals in groups II, III, and IV received FPB at 18.75, 37.5, and 75 mg/kg body weight/day p.o., respectively, for 21 days. FPB caused significant ( p < 0.05) increase in plasma biomarkers of renal and hepatic function (urea, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) when compared to control. Significant reductions in testicular ascorbic acid, glutathione, and activities of glutathione-S transferase, superoxide dismutase, and catalase were observed in FPB-treated animals when compared to control, in a dose-dependent manner. This was accompanied by increased testicular lipid peroxidation in the treated groups. Furthermore, a significant decrease in testicular acid phosphatase and γ-glutamyl transferase activities was also observed in the FPB-treated groups in a dose-dependent manner compared to control. However, testicular lactate dehydrogenase activity was significantly increased in the FPB-treated rats when compared to control. Additionally, histopathological studies revealed severe interstitial oedema and congestion of testicular blood vessels in the FPB-treated groups. Overall, data from this study suggest that FPB induced hepatotoxicity, nephrotoxicity, and oxidative stress-mediated alteration of testicular functions in rat.

Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI.

We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent. A CEST-FISP MRI protocol and a diamagnetic CEST agent were developed to detect GGT enzyme activity in biochemical solution. A quantitative Michaelis-Menten enzyme kinetics study was performed to confirm that catalyCEST MRI can measure enzyme activity. In vivo catalyCEST MRI studies generated pixel-wise activity maps of GGT activities. Ex vivo fluorescence imaging was performed for validation. CatalyCEST MRI selectively detected two CEST signals from a single CEST agent, whereby one CEST signal was responsive to GGT enzyme activity and the other CEST signal was an unresponsive control signal. The comparison of these CEST signals facilitated in vivo catalyCEST MRI studies that detected high GGT activity in OVCAR-8 tumors, low GGT activity in OVCAR-3 tumors, and low or no GGT activity in muscle tissues. CatalyCEST MRI with a diamagnetic CEST agent can detect the level of GGT enzyme activity within in vivo tumor models of human ovarian cancers. Magn Reson Med 77:2005-2014, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Recommendation to Exclude Bile-Duct-Cannulated Rats with Hyperbilirubinemia for Proper Conduct of Biliary Drug Excretion Studies.

Hyperbilirubinemia (HB) is sometimes encountered following bile-duct cannulation in rats. It possibly originates from the reduced functioning of multidrug resistance-associated protein 2 (Mrp2) and subsequent adaptive alterations in the expression of Mrp3 and the organic anion transporting polypeptides (Oatps). Our aim was to clarify the importance of excluding bile-duct-cannulated (BDC) rats with HB for proper conduct of drug excretion studies. We detected HB [serum total bilirubin concentration (TBIL) ≥0.20 mg/dl] in 16% of all BDC rats prepared. The serum activities of aspartate aminotransferase, alanine aminotransferase, leucine aminopeptidase, and alkaline phosphatase were within the respective normal ranges in the BDC rats with mild HB (TBIL, 0.20-0.79 mg/dl), indicating the absence of hepatic failure. In the pharmacokinetics of pravastatin, an Oatps/Mrp2 probe drug in the BDC rats, the apparent volume of distribution and the clearance were smaller in the mild HB group as compared with the normal group, suggesting the reduction of apparent hepatic uptake and hepatobiliary elimination. The biliary excretion (percentage of dose) was significantly reduced by 54%, suggesting that the biliary efflux activity via Mrp2 was reduced to a greater extent relative to metabolic activity in hepatocytes. The serum γ-glutamyltransferase (GGT) activity correlated with TBIL and inversely correlated with biliary excretion of pravastatin, a finding which could serve as a clue to uncover the regulatory system involving cooperation between GGT and Mrp2. In conclusion, BDC rats with HB, however mild, should be excluded from drug excretion studies to avoid the risk of underestimation of the biliary excretion of drugs.

The effect of occupational exposure on pro/antioxidant balance in the blood of non-smoking and smoking smelters with diabetes

Arsenic, lead and cadmium, potent environmental toxicants have been reported to induce diabetes mellitus, but their potential biological mechanism(s) have not been much investigated. The present study was designed to correlate parameters of pro/antioxidant balance with occupational exposure on heavy metals and smoking in smelters with diabetes compared on control group. The results showed a significant increase in the concentration of arsenic, cadmium and lead in the blood and urine of smelters, while smoking caused a further increase in the concentration of these metals. Increasing γ-glutamyltransferase activity and lead concentration due to occupational exposure in copper foundry, tobacco smoke and co-existing diabetes were observed. Also these factors have synergistic effects on metallothionein and glutathione concentrations as well as glutathione dependent enzymes activities. Our data suggests that sub-chronic arsenic, lead and cadmium exposure induces diabetic condition which may be mediated due to increased oxidative stress in blood.