Serum Glutamate Dehydrogenase Research Articles

Subcutaneous lysophosphatidylcholine administration promotes a febrile and immune response in Holstein heifer calves

Lysophosphatidylcholine (LPC) is immunomodulatory in nonruminants; however, the actions of LPC on immunity in cattle are undefined. Our objective was to study the effects of LPC administration on measures of immunity, liver health, and growth in calves. Healthy Holstein heifer calves (n = 46; age 7 ± 3 d) were randomly assigned to 1 of 4 treatments (n = 10 to 11 calves/treatment): a milk replacer diet unsupplemented with lecithin in the absence (CON) or presence of subcutaneously (s.c.) administered mixed (mLPC; 69% LPC-16:0, 25% LPC-18:0, 6% other) or pure LPC (pLPC; 99% LPC-18:0), or a milk replacer diet supplemented with 3% lecithin enriched in lysophospholipids containing LPC in the absence of s.c.-administered LPC (LYSO) for 5 wk. Calves received 5 s.c. injections of vehicle (10 mL of phosphate-buffered saline containing 20 mg of bovine serum albumin/mL; CON and LYSO) or vehicle containing mLPC or pLPC to provide 10 mg of total LPC per kilogram of BW per injection every 12 h during wk 2 of life. Calves were fed a milk replacer containing 27% crude protein and 24% fat at 1.75% of BW per day (dry matter basis) until wk 6 of life (start of weaning). Starter grain and water were provided ad libitum. Body measurements were recorded weekly, and clinical observations were recorded daily. Blood samples were collected weekly before morning feeding and at 0, 5, and 10 h, relative to the final s.c. injection of vehicle or LPC. Data were analyzed using a mixed model, with repeated measures including fixed effects of treatment, time, and their interaction. Dunnett's test was used to compare treatments to CON. Peak rectal temperatures were higher in mLPC or pLPC, relative to CON. Plasma LPC concentrations were greater in mLPC and LYSO calves 5 h and 10 h after the final injection, relative to CON. Calves receiving mLPC and pLPC also had higher circulating serum amyloid A concentrations, relative to CON. Calves receiving mLPC had greater serum aspartate aminotransferase, γ-glutamyltransferase, and glutamate dehydrogenase concentrations, relative to CON. Calves provided mLPC experienced lower average daily gain (ADG) after weaning, relative to CON. The LYSO treatment did not modify rectal temperatures, ADG, or measures of liver health, relative to CON. We conclude that LPC administered as s.c. injections induced an acute febrile response, modified measures of liver and immune function, and impaired growth in calves.

Treatment of animals with fatty liver disease using a drug based on the seeds of Silybum marianum

Medicinal plants are a source of various therapeutic preparations. Therefore, the aim of our work was to prepare a liposomal drug from extract from the seeds of Silybum marianum (L.) Gaertn., adding tocopherol acetate, lecithin, squalene, and Tween 80. The drug was used on the laboratory animals (rats) intramuscularly to measure the efficacy of treatment of experimentally modeled toxic fatty liver disease. The fatty infiltration of the liver in the rats was caused by tetrachloromethane (ССl4). The efficacy of the liposomal drug based on the extract from S. marianum seeds was studied on 25 animals in which the liver pathology had been caused by 50% oil solution of ССl4, administered in the dose of 5 mL per kg of body weight. The diseased rats were divided into five groups, each consisting five animals. Animals of the four experimental groups – first, second, third, and fourth - received the drug intramuscularly in the doses of 0.05, 0.25, 0.50, and 1.50 mL/kg of body weight three times every two days, respectively. At the same time, the control rats received three-time intramuscular injection of physiological solution in the dose of 0.5 mL/kg of body weight. Treatment of the animals with fatty liver disease by injections of the drug based on the extract from S. marianum seeds normalized the general condition, significantly improved the functions and structure of the liver. Biochemical studies of blood serum of the sick animals after the treatment revealed increase in albumin content, which may suggest reduction of the protein-synthesizing function of the liver. The normalization of the bile-forming and bile-excreting functions of the liver, and also elimination of cholestasis were evidenced by reduced contents of bile acids and total bilirubin and increased total cholesterol in the blood serum of the rats. After treating the animals with the created drug, we saw decrease in the activity of the liver-indicator enzymes (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and glutamate dehydrogenase) in the blood serum, which is a sign of recovery of the structure of hepatocytes and elimination of cytolysis. Histological studies of the liver of the treated rats confirmed the positive effect of the liposomal drug on the organ’s structure. In the future studies, we plan to test this combination of agents in treatment of agricultural and domestic animals with liver pathologies.

Serum levels of IL-6/IL-10/GLDH may be early recognition markers of anti-tuberculosis drugs (ATB) -induced liver injury

To explore the potential value of serum glutamate dehydrogenase (GLDH) combined with inflammatory cytokines as diagnostic biomarkers for anti-tuberculosis drug -induced liver injury (ATB-DILI). We collected the residual serum from the patients who met the criteria after liver function tests. We have examined these parameters including GLDH which were determined by enzyme-linked immunosorbent assay and cytokines which were determined by cytokine combination detection kit. Multivariate logistics stepwise forward regression was applied to establish regression models. A total of 138 tuberculosis patients were included in the diagnostic markers study of ATB-DILI, including normal liver function group (n = 108) and ATB-DILI group(n = 30). Serum GLDH, IL-6 and IL-10 levels were significantly increased in the ATB-DILI group. Receiver operating characteristic curve (ROC) curve showed that the area under curve (AUC) of serum GLDH, IL-6 and IL-10 for the diagnosis of ATB-DILI were 0.870, 0.714 and 0.811, respectively. In logistic regression modeling, the AUC of GLDH combined with IL-10 as an ATB-DILI marker is 0.912. Serum IL-6、IL-10 and GLDH levels began to rise preceded the increase in ALT by 7 days, with significant differences in IL-6 compared with 7 days. Serum GLDH, IL-6 and IL-10 levels were correlated with the severity of liver injury. In conclusion, we found that GLDH, IL-6 and IL-10 alone as diagnostic markers of ATB-DILI had good diagnostic efficacy. Logistic regression model established by GLDH and IL-10 had better diagnostic efficacy and IL-6 may be an early predictor of liver injury in the setting of ATB poisoning.

Glutamate dehydrogenase combined with ferrochelatase as a biomarker of liver injury induced by antituberculosis drugs.

To explore the potential value of serum glutamate dehydrogenase (GLDH), ferrochelatase (FECH), heme oxygenase-1 (HO-1) and glutathione-S-transferase-α (GST-α) as diagnostic biomarkers for liver injury caused by antituberculosis drugs. We established a rat model of isoniazide-induced liver injury and recruited 122 hospitalized tuberculosis patients taking antituberculosis drugs. We detected the concentration of GLDH, FECH, HO-1 and GST-α by enzyme-linked immunosorbent assay. GraphPad Prism8 and SPSS 26.0 were used for statistical analysis. In the rat model, serum GLDH concentration gradually increased during isoniazid (INH) administration, while serum FECH, HO-1 and GST-α concentrations significantly increased after INH administration was stopped. The receiver operating characteristic curve showed that the areas under the curve (AUCs) of serum GLDH and FECH for the diagnosis of anti-tuberculosis (TB) drug-induced liver injury (anti-TB-DILI) were 0.7692 (95% confidence interval [CI] 0.5442-0.9943) and 0.7284 (95% CI 0.4863-0.9705) and the diagnostic accuracies were 81.25% and 78.79%, respectively. In clinical research, the AUCs of GLDH and FECH were 0.9124 (95% CI 0.8380-0.9867) and 0.6634 (95% CI 0.5391-0.7877), and the optimal thresholds were 10.40 mIU/mL and 1.304 ng/mL, respectively. The diagnostic accuracy, specificity and positive predictive value (PPV) of GLDH were 82.61%, 79.38% and 47.22%. We performed a joint diagnostic test for GLDH and FECH. The diagnostic accuracy (90.43%), specificity (91.75%) and PPV (65.21%) of serial tests were better than for GLDH and FECH alone. GLDH in the diagnosis of liver injury induced by anti-TB drugs has high sensitivity, but low specificity and low PPV. The combination of GLDH and FECH could significantly improve the specificity, PPV and diagnostic accuracy, and reduce the false-positive rate of anti-TB-DILI.

Assessment of serum glutamate dehydrogenase activity and comparison to serum alanine aminotransferase activity in cats with increased blood total T4 concentration.

Glutamate dehydrogenase (GLDH), a key enzyme in amino acid oxidation and urea production, is mainly derived from the liver and its activity may increase with hepatocellular necrosis. Feline hyperthyroidism is associated with elevated serum activities of various enzymes, but the pattern of serum GLDH activity has not been reported, to our knowledge. Feline clinical biochemistry results from 2 commercial diagnostic laboratories were reviewed retrospectively to assess changes in serum GLDH activity in cats with significantly elevated serum total T4 concentrations, which is highly suggestive of hyperthyroidism. A total of 2,773 records were analyzed, of which 2,370 (85%) had normal total T4 (≤50 nmol/L) and 403 (15%) had increased total T4 (≥60 nmol/L) concentrations. Among cats with an increased total T4 concentration, 26.5% had increased serum GLDH activity. All cats with increased GLDH activity also had increased serum ALT activity. In 42.9% of cats, ALT activity was increased, but GLDH activity was normal. In 30.5% of cats, both serum GLDH and ALT activities were within RIs. The fold-increase of GLDH activity was almost half of the ALT fold-increase. Although serum GLDH activity increased in some cats with hyperthyroidism, serum ALT activity increased more frequently and to a greater extent.

Effects of prepartum supplementation of β-carotene on colostrum and calves.

Little is known about transfer of dietary β-carotene into colostrum, its absorption by the calf, and its effects on retinol and α-tocopherol in the calf when the dam's dietary vitamin A is adequate. Our objective was to assess the effect of β-carotene supplementation during the close-up dry period on the colostrum and calf. The study was conducted on a large commercial dairy farm in Indiana during early summer of 2015. Ninety-four multiparous Holstein cows were blocked by calving data, parity, and previous production, and then randomly assigned to either control or β-carotene (BC) treatments. While locked in headgates each morning, each cow received a topdress of β-carotene (Rovimix, DSM Nutritional Products, 8 g/d; provided 800 mg β-carotene) or carrier from 21 d before expected calving until calving. Colostrum was collected within 2 h of parturition. Calf blood samples were obtained within 2 h of birth before receiving the dam's colostrum, at 24 h after birth, and at 7 d and 60 d of age. Blood serum was analyzed for β-carotene, retinol, α-tocopherol, and other metabolites and enzymes. Colostrum was analyzed for β-carotene, retinol, α-tocopherol, colorimetry profile, and milk components. Data were analyzed using mixed-effects models in SAS (SAS Institute Inc.). Calf serum β-carotene data were analyzed using the FREQ procedure. Colostrum β-carotene was higher for BC cows. Colostrum from BC cows had increased a* [measures red (positive) to green (negative)] and b* [measures yellow (positive) to blue (negative)] colorimeter values, indicating that β-carotene altered colostrum color toward red and yellow. Supplementation did not affect colostral or calf IgG concentrations. Colostrum color indices were correlated with IgG concentrations as well as concentrations of β-carotene, retinol, and α-tocopherol. Before receiving colostrum, the concentration of β-carotene in calf serum was below the detectable threshold of 0.05 μg/mL. At 24 h of age, the number of calves with detectable β-carotene concentrations increased, with more calves from BC cows (52.1%) having detectable concentrations than calves from cows in the control group (6.1%). No differences in concentrations of retinol or α-tocopherol were observed in calf serum. Supplementation of β-carotene to cows decreased activities of gamma-glutamyl transpeptidase and glutamate dehydrogenase in calf serum. In pregnant cows already receiving adequate vitamin A, supplementation of β-carotene increased concentration of β-carotene in colostrum, altered colostrum color, and increased serum β-carotene in calves at birth.

Paraclinical Changes Occurring in Dairy Cows with Spontaneous Subacute Ruminal Acidosis under Field Conditions.

Simple SummarySubacute ruminal acidosis is a nutritional disorder that negatively impacts the health, performance, and welfare of dairy cows. This disease evolves subclinically over a long period of time, and finding suitable and easy-to-use biomarkers for early diagnosis is still a challenge for dairy practitioners. This study aimed to investigate the patterns of paraclinical changes and provide valuable data for more accurately identifying subacute ruminal acidosis under field conditions. Changes in certain blood and milk biochemical parameters were identified in this study, which, taken together, could provide a pattern of biochemical changes that would allow the easier identification of subacute ruminal acidosis in dairy cows under field conditions.This study was undertaken to investigate the changes in the blood and milk biochemical parameters found in naturally occurring and long-lasting spontaneous subacute ruminal acidosis (SARA), with the aim of identifying the patterns of paraclinical changes and providing valuable data for more accurately identifying SARA in cows under field conditions. The study was conducted on a dairy herd with a history of the occurrence of SARA-associated clinical signs. Twelve cows, between 20 and 150 days in milk, were randomly selected and subsequently subjected to venous blood, milk, and ruminal fluid collection. The mean pH value of the ruminal fluid was 5.56 ± 0.32, and 58% (7/12) of the tested cows were SARA positive (ruminal pH ≤ 5.5). The albumin, calcium, and phosphorus serum concentration values were significantly lower (p < 0.05) in the SARA group than in the group of healthy cows. Serum aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) activity were significantly higher in the SARA cows (p < 0.05) than in the group of healthy cows. The mean values of milk fat, milk protein content, and milk fat-to-protein ratio were significantly lower (p < 0.05) in the tested cows of the SARA group than in the healthy group of cows. In conclusion, the results of the current study indicate that long-term SARA triggered by a high-concentrate diet is associated with clinically significant changes in both the blood composition (hypoalbuminemia, hypocalcemia, and increased serum AST and GLDH activity) and the milk composition (decreased fat and protein percentage and milk fat-to-protein ratio). Altogether, the obtained results provide a more reliable pattern of paraclinical changes and useful insights for detecting SARA in dairy cows under field conditions.

Investigation of serum enzyme activities and oxidative stress markers in preeclampsia: a multiparameter analysis.

Preeclampsia, a high cause of fetomaternal morbidity-mortality, remains a significant burden affecting 8% of all pregnancies. Environmental conditions induce disease development leading to endothelial dysfunction in genetically predisposed women. Our aim is to discuss oxidative stress as a well-established contributing factor to disease progression with being the first study to show new evidence about serum dehydrogenase enzyme levels (isocitrate, malate, glutamate dehydrogenase) with oxidative markers (myeloperoxidase, total antioxidant-oxidant status, oxidative stress index). Serum parameters were analyzed with photometric method (Abbott ARCHITECT c8000). The enzyme levels and oxidative markers were significantly higher in patients, supporting the redox imbalance in preeclampsia. According to ROC analysis, malate dehydrogenase showed an outstanding diagnostic ability with the highest AUC value of 0.9 and the cut-off value of 51.2 IU/L. Discriminant analysis including malate, isocitrate and glutamate dehydrogenase had predicted preeclampsia with an overall 87.9% accuracy. Considering the above results, we propose that the enzyme levels increase with oxidative stress functioning as antioxidant defense factors. The unique finding of the study is that the serum levels of malate, isocitrate and glutamate dehydrogenase can be used both separately and combined in the early prediction of preeclampsia. As a novel approach, we also offer combining serum isocitrate and glutamate dehydrogenase levels with ALT, AST tests to state liver functions more reliably in patients. Still, larger sample-sized studies investigating enzyme expression levels are required to confirm the recent findings and to reveal underlying mechanisms.

Serum haptoglobin concentration and liver enzyme activity as indicators of systemic inflammatory response syndrome and survival of sick calves.

BackgroundIncreased concentration of haptoglobin (Hp) in serum is associated with survival of critically ill humans and horses. High serum activity of liver‐derived enzyme is associated with sepsis in children and foals.Hypothesis/ObjectivesInvestigate whether admission serum Hp and glutamic dehydrogenase (GLDH) are associated with systemic inflammatory response syndrome (SIRS) and survival of sick calves.AnimalsOne hundred two calves.MethodsRetrospective cross‐sectional study. Electronic medical records from all calves <30 days of age admitted to a teaching hospital for 8 years were reviewed. The signalment, clinicopathological findings, the presence of SIRS, final diagnosis, hospitalization time and outcome were recorded. A Cox proportional hazard ratio (HzR) were calculated to assess the association between clinicopathological variables and survival to discharge.ResultsSerum Hp concentrations were similar between SIRS (0.29 g/L; range, 0.05‐3.6) and non‐SIRS calves (0.22 g/L; range, 0‐4.2; P = .62). GLDH activity was similar between SIRS (12 U/L; range, 1‐1025) and non‐SIRS calves (9 U/L; range, 2‐137; P = .2). Absent suckle reflex (HzR: 6.44, 95% CI: 1.44‐28.86), heart rate (HR) < 100 beats per minute (bpm; HzR: 12.2; 95% CI: 2.54‐58.62), HR > 140 bpm (HzR: 3.59, 95% CI: 1.05‐12.33), neutrophil count <1.7 × 109/L (HzR: 7.36; 95% CI: 2.03‐26.66) and increased gamma‐glutamyl transferase activity (every 50‐unit, HzR: 1.12; 95% CI: 1.03‐1.21) were predictive of nonsurvival.Conclusions and Clinical ImportanceThe use of Hp and GLDH for prediction of survival in sick calves cannot be recommended at this time.

Effects of Bacillus subtilis ZJ-2019-1 on Zearalenone Toxicosis in Female Gilts.

The purpose of this research was to investigate the toxicity of zearalenone (ZEN) on the growth performance, genital organs, serum hormones, biomarkers, and histopathological changes of female gilts and to evaluate the efficacy of Bacillus subtilis ZJ-2019-1 in alleviating ZEN toxicosis in gilts. Twenty-four female gilts were randomly allocated to four groups with six replicates per group and one gilt per replicate, fed on four feeds prepared previously, which were basic diet (control group, C group), ZEN diet (Z group), Zlb diet (Zlb group) containing B. subtilis ZJ-2019-1 in liquid form, and Zdb diet (Zdb group) containing B. subtilis ZJ-2019-1 in dehydrated form. The results showed that the vulva size and relative weight of reproductive organs had no significant difference in the control group, Zlb group, and Zdb group, but were significantly lower than in the Z group (p < 0.05); the relative weight of the liver was lower in the C group, Zlb group, and Zbd group than in the Z group (0.05 < p < 0.1). The concentration of serum glutamate dehydrogenase (GLDH) was lower, but follicle-stimulating hormone (FSH) was higher in the Z group, Zlb group, and Zdb group than in the Z group (0.05 < p < 0.1). Additionally, serum luteinizing hormone (LH) concentration had no significant difference in the C group, Zlb group, and Zdb group but was significantly lower than in the Z group (p < 0.05); estradiol (E2) was significantly lower in the Zlb group and Zdb group than that in C group, but significantly higher than that in Z group (p < 0.05); PRL was significantly higher in the Zlb group and Zdb group than in the C group, but was significantly lower than in Z group (p < 0.05). ZEN and its reduced metabolites were measured in biological samples after enzymatic hydrolysis of the conjugated forms. The concentration of serum ZEN and its metabolite, α-zeralenol (α-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05); urine ZEN and its metabolites, α-ZOL and β-zeralenol (β-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05). Cell damages were observed in the liver, uterus, and ovary of gilts in the Z group and alleviated in Zlb and Zdb groups, but the loss of oocytes was irreversible in the ovary. The ZEN-contaminated diet caused serious changes in female hormones and brought harm to the livers and reproductive organs, but B. subtilis ZJ-2019-1 could naturally remove the ZEN significantly, which ameliorated the reproductive impairment in gilts caused by ZEN. The addition of B. subtilis ZJ-2019-1 to ZEN-contaminated feeds could ameliorate the toxic effects effectively, regardless of liquid or dry culture. Therefore, the B. subtilis ZJ-2019-1 strain has great potential industrial applications.

The predictive role of preoperative serum glutamate dehydrogenase levels in microvascular invasion and hepatocellular carcinoma prognosis following liver transplantation-a single center retrospective study.

BackgroundAs a critical metabolic substrate, glutamine is not only involved in the progression of many cancers but is also related to angiogenesis. Glutamate dehydrogenase (GLDH), a key enzyme in glutamine metabolism, has been reported to regulate tumor proliferation; however, its relationship with microvascular invasion (MVI) is unclear. This study evaluated the ability of preoperative serum GLDH levels to predict MVI and the long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (LT).MethodsHCC patients that underwent LT from January 2015 to May 2020 at the First Affiliated Hospital of Sun Yat-Sen University were enrolled in our retrospective analysis. Clinicopathological variables were extracted from medical records. A receiver operating characteristic curve was created to determine the optimal cut-off value of GLDH for MVI.ResultsPreoperative GLDH was significantly elevated in the MVI-positive group (U = 454.00, p = 0.000). The optimal cut-off value of GLDH for MVI was 7.45 U/L, with an area under the curve of 0.747 (95% CI [0.639–0.856], p = 0.000). The sensitivity was 79.3%, while the specificity was 64.5%. GLDH > 7.45 U/L (p = 0.023) and maximum diameter >5 cm (p = 0.001) were independent risk factors for the presence of MVI. Patients with GLDH > 7.45 U/L had significantly poorer overall survival (p = 0.001) and recurrence-free survival (p = 0.001) after LT than patients with GLDH ≤ 7.45 U/L. Similarly, patients with MVI were associated with poor survival (p = 0.000).ConclusionsPreoperative elevated serum GLDH levels predict MVI and poorer long-term survival for HCC after LT.

Systemic implications of metallic foreign body syndrome in dairy cattle

This study aimed to evaluate the systemic implications of 37 cattle with traumatic reticulitis, evaluating clinical, laboratory, ultrasonographic and necroscopic changes. A clinical, laboratory and ultrasonographic examination was performed, and the animals were distributed in reticuloperitonitis (GI; n=21) and reticulopericarditis (GII; n=16) traumatic, based on necropsy findings. Blood samples were taken for haematological tests, serum total protein, albumin, globulin, gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), creatinine, urea, cortisol, creatine kinase (CK), creatine kinase-MB (CK-MB), cardiac troponin-I (cTn-I), plasma glucose and L-lactate. The abdominocentesis was productive in eight GI (n=8) and seven GII (n=7) animals, allowing the evaluation of physical, cytological and biochemical characteristics of the peritoneal fluid as a total protein, albumin, GLDH, AST, GGT, glucose and L-lactate. Changes in behavior, appetite, dehydration and temperature were observed, most expressive in GII. Hematology showed neutrophilic leukocytosis with regenerative left shift and hyperfibrinogenemia in both groups. Increased globulin, L-lactate concentration and serum GGT, GLDH, CK and CK-MB activity were observed, as well as significant elevation of cTnI (p=0.0190) in GII. In the peritoneal fluid exudate was observed in both groups and a higher concentration of L-lactate in relation to plasma. Ultrasound revealed retocular, cardiac, hepatic and splenic abnormalities. The anatomopathological lesions confirmed the ultrasound findings of both groups. The understanding of the syndrome helps in the diagnosis, as well as the adoption of preventive measures, minimizing the economic impact caused to the dairy cattle breeding.

Enzymatic and fecundity evaluation of Fasciola hepatica exposed to different doses of γ- irradiation in Ethiopian sheep

The upshot of γ-irradiated Fasciola hepatica infection on the activity of plasma glutamate dehydrogenase (GLDH) and γ-glutamyl transpeptidase (GGT) was evaluated in 36 sheep infected with a single dose of 30, 60, 120, and 240 grays and those kept as negative and positive control over 17 weeks. During this period, serum and faecal samples, as well as body weight gains, were taken at weekly intervals. Furthermore, the effects of the irradiation dose (500) for oral vaccination and on the recovery of adult flukes were assessed following primary infection. Eggs were first detected in the faeces of infected sheep on week 8 post-infection. The parasite viability was severely affected by doses of γ-irradiation of 120 Gy or 240 Gy. In the aforementioned doses, relatively low numbers of mature flukes of about 60 (17.1%) and 38 (10.8%) were recovered than the control group, respectively. The sensitized lambs also showed less hepatic damage compared with the controls as indicated by lower levels of the serum enzyme glutamate dehydrogenase and γ- glutamyl transferase significant body weight loss was observed between weeks 6 and 8 post-infection followed by a steady increase of the mean weight of infected animals across time. In conclusion, vaccination of sheep with γ irradiated metacercariae of F. hepatica appeared to affect the number and development of the fluke population resulting in reduced hepatic damage during migration, reduced fecundity after patency, as measured by worm and egg counts, levels of serum glutamate dehydrogenase and γ- glutamyl transferase.

Transformation of fish waste protein to Hermetia illucens protein improves the efficacy of poultry by-products in the culture of juvenile barramundi, Lates calcarifer

Promoting a circular economy via the transformation of food waste into alternative and high-value protein sources for aquaculture diets is a novel approach to developing alternative raw materials to fishmeal (FM). This approach can reduce the ecological impact on the aquatic environment and simultaneously can provide an option for sustainable food waste management. In this context, we report a 56-day trial of feeding barramundi, Lates calcarifer on four iso‑nitrogenous and iso-lipidic diets where the control (0PBM-0HI) was a FM-based diet and the other test diets replaced FM protein with mixtures of a poultry by-product meal (PBM) and a full-fat Hermetia illucens (HI) larvae meal reared on fish waste: the test diets were 85% PBM + 15% HI (85PBM-15HI), 80% PBM + 20% HI (80PBM-20HI) and 75% PBM + 25% HI (75PBM-25HI). Fish fed PBM-HI-based diets showed an equal growth rate and amino acid profile when compared to the control group. Among all serum metabolites, alanine aminotransferase and glutamate dehydrogenase decreased in fish fed PBM-HI-based diets, whilst total protein levels improved in the same diets. Serum lysozyme and bactericidal activity were unchanged which supported the observation of similar infection rates against V. harveyi. Except for the kidney and intestine, catalase activity in the serum and liver increased in fish-fed PBM-HI-based diets. In assessing the gastrointestinal mucosal morphology, the goblet cells producing neutral mucins were higher in PBM-HI-fed fish than the control. PBM-HI diets also enhanced bacterial richness and diversity and increased abundance for Lactobacillus, Clostridium, and Ruminococcus. In summary, combining full-fat HI with PBM allowed complete replacement of FM with no negative effects on growth whilst improving gut health. Such diets would be beneficial for the aquaculture industry, both ecologically and economically, as well as providing value-adding to animal waste as alternative protein sources for aquafeed production.

Intravenous trimethylamine N-oxide infusion does not modify circulating markers of liver health, glucose tolerance, and milk production in early-lactation cows

In rodents and humans, the gut bacteria-derived metabolite trimethylamine N-oxide (TMAO) has been implicated in the progression of cardiovascular disease, chronic kidney disease, fatty liver, and insulin resistance; however, the effects of TMAO on dairy cattle health and milk production have not been defined. We aimed to determine whether intravenous TMAO infusion modifies measures of liver health, glucose tolerance, and milk production in early-lactation cows. Eight early-lactation Holstein cows (30.4 ± 6.41 d in milk; 2.88 ± 0.83 lactations) were enrolled in a study with a replicated 4 × 4 Latin square design. Cows were intravenously infused TMAO at 0 (control), 20, 40, or 60 g/d for 6 d. Washout periods lasted 9 d. Intravenous glucose tolerance tests (GTT) occurred on d 5. Blood was collected daily. Milk was collected on d -1, 0, 5, and 6. Urine was collected on d -1 and 6. Circulating metabolites, milk components, and TMAO concentrations in milk, urine, and plasma were quantified. Data were analyzed using a mixed model that included the fixed effects of treatment. Concentrations of TMAO in plasma, milk, and urine increased linearly with increasing dose. Dry matter intake and milk production were not modified by treatment. Daily plasma triacylglycerol, fatty acid (FA), and glucose concentrations were not modified. Serum albumin, total protein, globulin, total bilirubin, direct bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and glutamate dehydrogenase concentrations were also not modified by treatment. Serum GTT glucose, FA, and insulin concentrations were not modified by treatment. Plasma total, reduced, and oxidized glutathione concentrations were also not modified by treatment. We conclude that a 6-d intravenous infusion of TMAO does not influence measures of liver health, glucose tolerance, or milk production in early-lactation dairy cows.

Disruption of endoplasmic reticulum homeostasis exacerbates liver injury in clinically ketotic cows

Disruption of endoplasmic reticulum (ER) homeostasis, a condition termed "ER stress," contributes to the development of liver injury in nonruminants. Because liver injury is a prominent pathological feature associated with overproduction of ketone bodies in dairy cows with ketosis, understanding the ER stress state and its functional consequences on liver injury is of particular interest. Here, 30 multiparous cows (within 3 wk postpartum) classified based on blood β-hydroxybutyrate (BHB) as healthy (n = 15, BHB <0.6 mM) or clinically ketotic (n = 15, BHB >3.0 mM) were used. Compared with healthy cows, ketotic cows had greater levels of serum fatty acids and activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, and glutamate dehydrogenase but lower serum glucose. Furthermore, dairy cows with ketosis had greater protein abundance of ER stress markers in liver tissue, including protein kinase RNA-like ER kinase (PERK), inositol-requiring protein-1α (IRE1α), and cleaved activating transcription factor-6 (ATF6). Cows with ketosis also had higher mRNA levels of hepatic 78-kDa glucose-regulated protein (GRP78) and spliced X-box binding protein 1 (sXBP1). These data confirmed an enhanced ER stress state in clinically ketotic cows. To explore whether enhanced hepatic ER stress was induced by elevated ketone bodies and the possible contribution of ER stress to liver injury, in vitro experiments were then performed using isolated primary calf hepatocytes treated with incremental concentrations of BHB (0, 0.6, 1.2, 3.0, and 4.8 mM) for 12 h with or without overexpression of GRP78 (the master regulator of unfolded protein response). Phosphorylation levels of PERK and IRE1α proteins, level of cleaved ATF6 protein, and mRNA abundance of GRP78 and sXBP1 in hepatocytes increased after treatment with high (3.0 and 4.8 mM) BHB, indicating a mechanistic link between excessive BHB and enhanced hepatic ER stress. Furthermore, treatment with 3.0 and 4.8 mM BHB markedly elevated activities of aspartate aminotransferase and alanine aminotransferase in cell supernatant, indicating exacerbated hepatocyte damage after ER stress was enhanced. Overexpression of GRP78 attenuated both BHB-induced ER stress and the ensuing cellular damage, suggesting that hepatocyte damage caused by excessive BHB can be mediated via enhanced ER stress. Overall, the present study revealed that ER stress may exacerbate liver injury development in clinically ketotic cows, underscoring the biological relevance of this pathway in the context of liver injury.

Clinical and laboratory findings in sheep experimentally poisoned by Palicourea marcgravii and the use of magnesium chloride with possible therapeutic effect on poisoning

ABSTRACT: This study aimed to examine the efficacy of magnesium chloride therapy in sheep experimentally poisoned by Palicourea marcgravii and describe the clinical and laboratory findings that may aid in early ante mortem diagnosis of this poisoning. P. marcgravii is an important plant within a group of 22 species in Brazil that cause “sudden death.” Its toxic component is sodium monofluoroacetate. It was observed that a time for evolution of poisoning was longer in our study compared to other studies that used the same dose of P. marcgravii in sheep. However, all animals that were poisoned and subsequently treated with magnesium chloride died. The sheep presented characteristic clinical signs before death in addition to other signs that have not been previously described for this type of poisoning, such as abdominal breathing, coughing, head pressing, and nystagmus. This is the first evaluation of hematological parameters of sheep poisoned by P. marcgravii. Leukocytosis with neutrophilia, hyperfibrinogenemia, and hyperglycemia, associated with hypophosphatemia and elevated levels of serum aspartato aminotransferase (AST), glutamate dehydrogenase (GLDH), urea, creatinine, creatine kinase (CK) and lactate dehydrogenase (LDH), were observed. Additionally, changes were noted in necropsy, such as engorged jugular, large vessel congestion, pulmonary edema. Histological examination revealed vacuolar hydropic degeneration in the distal twisted uriniferous tubules in the kidneys, similar to those reported in previous studies on P. marcgravii poisoning.

Post-treatment with glycyrrhizin can attenuate hepatic mitochondrial damage induced by acetaminophen in mice.

Overdose of acetaminophen (APAP) is responsible for the most cases of acute liver failure worldwide. Hepatic mitochondrial damage mediated by neuronal nitric oxide synthase- (nNOS) induced liver protein tyrosine nitration plays a critical role in the pathophysiology of APAP hepatotoxicity. It has been reported that pre-treatment or co-treatment with glycyrrhizin can protect against hepatotoxicity through prevention of hepatocellular apoptosis. However, the majority of APAP-induced acute liver failure cases are people intentionally taking the drug to commit suicide. Any preventive treatment is of little value in practice. In addition, the hepatocellular damage induced by APAP is considered to be oncotic necrosis rather than apoptosis. In the present study, our aim is to investigate if glycyrrhizin can be used therapeutically and the underlying mechanisms of APAP hepatotoxicity protection. Hepatic damage was induced by 300 mg/kg APAP in balb/c mice, followed with administration of 40, 80, or 160 mg/kg glycyrrhizin 90 min later. Mice were euthanized and harvested at 6 h post-APAP. Compared with model controls, glycyrrhizin post-treatment attenuated hepatic mitochondrial and hepatocellular damages, as indicated by decreased serum glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities as well as ameliorated mitochondrial swollen, distortion, and hepatocellular necrosis. Notably, 80 mg/kg glycyrrhizin inhibited hepatic nNOS activity and its mRNA and protein expression levels by 16.9, 14.9, and 28.3%, respectively. These results were consistent with the decreased liver nitric oxide content and liver protein tyrosine nitration indicated by 3-nitrotyrosine staining. Moreover, glycyrrhizin did not affect the APAP metabolic activation, and the survival rate of ALF mice was increased by glycyrrhizin. The present study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as drug for the treatment of APAP hepatotoxicity.

Nagapashana Pishti - A Potent Cardio Tonic

Nagapashana (Serpentine), a hydrous silicate of Magnesium (Mg6 (Sio10) OH8), is an important mineral drug used in Ayurveda, often in the form of Pishti (fine powder of Nagapashana). It is a Hrudya Dravya (cardiotonic). It is particularly indicated in Hrud Dourbalyaa, a condition associated with weakness of cardiac muscles. Cardiovascular disease is a leading cause of death in developed and developing countries. The present study was conducted to evaluate the cardio tonic activity of Nagapashana Pishti on Wistar rats. In the in-vivo study, Doxorubicin (2mg/kg) for 7 days was used to induce cardiac damage and the cardio tonic effect of Nagapashana Pishti at a dose of 150 and 300 mg/kg.b.w, was compared with standard drug Digoxin. Biochemical assays like serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), Total Cholesterol (TC), Triglyceride (TG) and Creatine kinase Monoenzyme B (CKMB) were done together with histopathology of heart tissue and ECG analysis. The in-vivo study revealed that Nagapashana Pishti (300mg/kg) was relatively more effective due to decreased QT and ST interval in ECG, significantly reduced levels of serum CKMB, SGOT, SGPT, TC and LDH and improvement in myocardial tissue.

Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments

Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.