Significant Increase In Alanine Aminotransferase Research Articles

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Mama decoction (MD) is a commonly used formulated herbal product in Nigeria for the management of malaria; no study on its central and possible toxicological effects have been investigated, hence this study. MD was administered orally to rats at 143, 286, and 572 mg/kg daily for 30 days. Novelty-induced behavior was observed and recorded on both day 1 and day 30 of administration. Furthermore, mortality, biochemical and histopathological tests were evaluated appropriately. The animals were sacrificed on day 30 after the behavioral scoring and blood samples obtained for biochemical assays. Histopathological examinations of the liver, kidney, brain, spleen, testes and lungs were carried out. The results showed that acute oral administrations of MD had no significant effect on locomotion at all dose levels used on Day 1 while during the subchronic administration of MD, only the dose of 286 mg/kg had significant effect on locomotion. Furthermore, the grooming behavior was significantly (p<0.01) decreased dose-dependently. Biochemical analysis showed that sub-chronic administration of MD caused significant decrease in both triglyceride and cholesterol levels but caused a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the plasma. In the liver, triglyceride, cholesterol and ALT were significantly decreased while AST was significantly increased but it had no effect on the ALP. The histopathological analysis revealed that most of the organs were essentially normal. In conclusion, the study showed that oral administration of MD is relatively safe when used within the recommended maximum dose of 286 mg/kg, however, there is need for caution in using it for a long period. Key words: Azadirachta indica, Alstonia boonei, Morinda lucida, Mangifera indica,biochemical, sub-chronic toxicity.

Preliminary study of the level of visfatin and the relationship with insulin resistance in Chinese patients with chronic hepatitis C.

Many studies have suggested that visfatin expression is closely related to the occurrence of insulin resistance (IR), while the precise role of visfatin in the regulation of IR in chronic hepatitis C (CHC) is not clear. We investigated fasting glucose, fasting insulin (FINS), C peptide, visfatin, visfatin mRNA, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and other parameters of 315 patients with CHC and 150 control cases in China. Meanwhile we collected clinical and other laboratory data for further analysis. Compared with the control group, the CHC group had a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST to platelet ratio index (APRI), ratio of AST to ALT (AAR), gammaglutamyl trans-peptidase, IL-6, TNF-α, visfatin, visfatin mRNA, FINS, fasting C peptide, and IR index. The visfatin, visfatin mRNA, insulin, IR index, Homaβ cell function index (HBCI), and fasting β-cell function index (FBCI) of the subjects with high body mass index (BMI) from the CHC sub-group were significantly higher than the normal BMI sub-group of CHC patients. We found a positive correlation between visfatin, visfatin mRNA and BMI, IL-6, TNF-α, and IR index. Our data suggest that visfatin may be related to IR in Chinese CHC patients.

The Association between Oxidative Stress and Metabolic Syndrome in Adults

BackgroundIn this Study, we investigated the effects of lifestyle and metabolic syndrome on free oxygen radical levels in men and women in Korea.MethodsA total of 254 adults were included in this study from February 2011 to June 2012 at a health promotion center. Information of the lifestyles and presence of metabolic syndrome factors was obtained. Biochemical markers were measured and free oxygen radicals test (FORT) was performed on the blood.ResultsOf the 254 subjects, 86 (33.9%) had metabolic syndrome, and 187 (73.6%) were men. Between the subjects with and without metabolic syndrome, there was a significant increase in alanine aminotransferase and serum FORT values in the subjects with metabolic syndrome. Multiple linear regression analysis showed that high-sensitivity C-reactive protein (hs-CRP) (P = 0.004), metabolic syndrome (P = 0.037), and female gender (P = 0.030) were independent predictors of serum FORT values. The subjects with high fasting blood sugar level or low high density lipoprotein cholesterol levels showed high serum FORT values.ConclusionHigh hs-CRP, the presence of metabolic syndrome, and female gender were associated with the high oxidative stress. High oxidative stress was associated with the presence of metabolic syndrome.

Haematological and biochemical analysis in canine enteritis

Aim: The present investigation screened eighteen clinical cases of canine enteritis for haematological and biochemical analyses. Materials and Methods: Eighteen dogs suffering from enteritis were selected and detailed clinical manifestations were noted. Hematological and biochemical parameters were estimated by using various kits. Blood was also collected from twelve healthy dogs for establishing control values and data obtained were subjected to statistical analysis. Results: The affected dogs showed anorexia, diarrhoea, depression, varying degree of dehydration and tachycardia. There were significant changes in packed cell volume, neutrophils, lymphocytes and mean corpuscular haemoglobin concentration. Biochemical investigation revealed significant decrease in plasma glucose, total plasma protein, albumin and albumin:globulin ratio (A:G ratio). The level of potassium and chloride was markedly decreased. Significant increase in alanine aminotransferase (ALT) and blood urea nitrogen (BUN) was observed. Conclusion: Packed Cell Volume (PCV) and Total Erythrocyte Count (TEC) remained almost similar between healthy dogs and dogs affected with diarrhoea. Mean Total Leukocyte Count (TLC) value was significantly higher as compared to the control group. Hypoglycemia, hypoproteinemia, hypokalemia, hypochloremia and increase in blood urea nitrogen was observed in dogs suffering from enteritis.

Effects of long-term exposure to simazine in real concentrations on common carp ( Cyprinus carpio L.)

The effects of a 90 day simazine exposure at concentrations of 0.06 (reported concentration in Czech rivers), 1, 2, and 4 μg L −1 were assessed in one-year-old common carp ( Cyprinus carpio L.). Its influence on biometric parameters, hematology, blood biochemistry, liver biomarkers, and histology was investigated. Biometric parameters of common carp exposed to simazine at 0.06 μg L −1 showed no differences from untreated fish. Simazine concentrations of 1, 2, and 4 μg L −1 caused significant ( p<0.01) increase of hepatosomatic indices relative to controls. Hematological profiles showed significant ( p<0.01) decrease in leukocyte count relative to controls at all concentrations. Biochemical profiles of common carp exposed to simazine at all concentrations showed significant ( p<0.01) increase in activity of alkaline phosphatase. In addition, at concentrations of 1 and 2 μg L −1, there was a significant increase in alanine aminotransferase ( p<0.05), and, at 4 μg L −1, a significant increase in total protein ( p<0.05), albumins ( p<0.05), and alanine aminotransferase ( p<0.05) compared with controls. Renal histology revealed severe hyaline degeneration of the epithelial cells of caudal kidney tubules in fish at all exposure levels compared to controls. Chronic exposure of common carp to simazine caused significant shifts in hematological, biochemical, and biometric profiles, and histopathological changes. The results of this study indicate that chronic exposure of simazine has altered multiple physiological indices in fish hematology and biochemistry, which potentially may be a biomarker of simazine toxicity; however, before these parameters are used as special biomarkers for monitoring residual simazine in aquatic environment, more detailed experiments in laboratory need to be performed in the future.

P27 Reduction in alanine aminotransferase values in diabetic patients receiving long-term oral antibiotics: does modulation of gut flora affect hepatic inflammation in non-alcoholic fatty liver disease?

IntroductionThe gut microbiota may play a role in host metabolic processes and have been linked to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Murine studies have suggested beneficial effects...

Involvement of Th2 cytokines in the mouse model of flutamide‐induced acute liver injury

Drug-induced liver injury is a growing concern for pharmaceutical companies and patients because numerous drugs have been linked to hepatotoxicity and it is the most common reason for a drug to be withdrawn. Flutamide rarely causes liver dysfunction in humans, and immune allergic reactions have been suggested in some cases. In this study, we investigated the mechanisms of flutamide-induced liver injury in BALB/c mice. Plasma alanine aminotransferase and aspartate aminotransferase levels were significantly increased 3, 6 and 9 h after flutamide (1500 mg kg⁻¹ , p.o.) administration. The biomarker for oxidative stress was not changed, but Th2-dominant immune-related factors, such as interleukin (IL)-4, IL-5, STAT6 and GATA-binding protein (GATA)-3, were induced in flutamide-administered mice. The pre-administration of monoclonal-IL-4 antibody suppressed the hepatotoxicity of flutamide. In addition, we investigated the effect of 13,14-dihydro-15-keto-PGD₂ (DK-PGD₂; 10 µg per mouse, i.p.) administration on flutamide-induced acute liver injury. Coadministration of DK-PGD₂ and flutamide resulted in a significant increase in alanine aminotransferase and a remarkable increase of macrophage inflammatory protein-2. In conclusion, we demonstrated that flutamide-induced acute liver injury is mediated by Th2-dominant immune responses in mice.

Dose-dependent effect of histamine on liver function markers in immunized rabbits

The present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits. The cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n=18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1×10(9) cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined. Groups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p<0.05). Short-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.

Ethanol Potentiates the Acute Fatty Infiltration of Liver Caused by Burn Injury: Prevention by Insulin Treatment

Burn injury is a significant and severe representation of critical illness. Nearly, 50% of patients admitted to hospitals for burn injuries have detectable levels of ethanol in their circulations and these patients have poorer clinical outcomes than burned individuals without measurable circulating ethanol. We report here data on a clinically relevant form of hepatic injury, the development of microvesicular steatosis, in a murine model wherein animals were either given ethanol or saline, and were subjected to burn or sham injury. Because better glycemic control with insulin has been shown in clinical studies to impart major clinical benefit, an additional group of burn ethanol animals were treated with insulin. Insulin significantly reduced blood glucose in injured animals to levels no different from those seen in animals that were neither ethanol exposed nor burned. A single intraperitoneal injection of ethanol was insufficient to raise blood alanine aminotransferase (ALT), measured as an index of liver injury. However, burn injury led to significant increases in ALT at 24 and 48 hours, which had returned to preinjury levels by 7 days. This ALT rise was completely prevented with insulin treatment. A single injection of ethanol did not evoke increased microvesicular steatosis but did potentiate the ability of burn to do so at 24 hours after injury. The burn induced increase in microvesicular steatosis was also seen at 48 hours, but had subsided by 7 days. The increased microvesicular steatosis was prevented by insulin therapy. Thus, ethanol potentiates the ability of burn to cause acute liver injury, which is completely preventable by insulin therapy. These findings may have substantial clinical significance and suggest this model may be useful for the study of the mechanisms of hepatic injury as well as the mechanisms, probably multiple, of insulin action in this setting.

The clinical, biochemical, haematological and pathological effects of long-term administration of Ipomoea carnea to growing goats.

Ipomoea carnea has been held responsible for several poisoning episodes, mainly in goats. This plant contains swainsonine, which inhibits acid or lysosomal alpha-mannosidase enzyme, causing cellular vacuolization. The objective of this study was to evaluate I. carnea toxicosis when four different doses of this plant were fed to growing goats. Twenty-five male goats were divided into five groups, one control group and four experimental groups that received 2.5, 5.0, 10.0 and 30.0 g of the plant per kg of live weight per day for 4 months. Blood samples were collected for haematological and biochemical determinations and fragments from some tissues were collected for histopathological study. All the experimental goats ingested the plant throughout the trial, presenting nystagmus, muscle tremors, weakness of the hind limbs and ataxia. They also had a significant increase in alanine aminotransferase (ALT) from the sixth week of the experiment compared to the goats in the control group. There was a significant reduction in haemoglobin concentration in the goats treated with I. carnea. Histopathology revealed degenerative vacuolar alterations in the liver, pancreas, thyroid and kidney cells, and in the neurons of the central nervous system in the animals that received the plant. All these alterations occurred in a dose-dependent manner.

The effect of benzene on serum hormones and the activity of some enzymes in different tissues of rats

The effects of a 100 mg.kg -1 dose of benzene, an occupational and environmental toxicant, were investigated on serum, estradiol and testosterone concentrations as well as lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), and pyruvate kinase (PK) activities in the liver and kidney of rats after 2, 4, 8, 16, 32, 64 and 72 hours. Benzene was given intraperitoneally to Rat rattus norvegicus and the control groups were injected with physiological saline. Liver tissue LDH, AST, ALT and kidney tissue LDH, ALP, AST, ALT activities were lower in the benzene treated group when compared to those in the control group (p<0.05). A tendency for an increase in the liver tissue ALP activity was observed, which was significant at 8 and 16 hours (p<0.05). There were significant increases in ALT in the liver and LDH, AST, and ALT enzyme activities in the kidney tissue at the beginning of the experiment in both groups and these activities were found to be nearly the same. Pyruvate kinase enzyme activities in rats given benzene were slightly increased in kidney tissues but lower in liver tissues. Differences between the groups tended to disappear towards the end of the experimental period. However, serum estradiol concentrations in the serum diverged significantly (p<0.05). Consequently, it was found that benzene administration led to some changes (increases then decreases) in LDH, ALP, ALT, AST, and PK activity and estradiol, testosterone concentrations in different tissues of rats. Possible causes of the increases and decreases in enzyme activities and hormone levels are discussed.

Safety evaluation of olive phenolic compounds as natural antioxidants

Free and total polyphenolic compounds were extracted from the fruits and leaves of the Picual cultivar. The safety limits of these compounds were recognized by measuring the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of high-density lipoprotein (HDL) cholesterol and total lipids of rat serum. The free and total phenolic compounds (400, 800, and 1600 ppm) and butylated hydroxy toluene (BHT) (200 ppm) were daily ingested for 7 weeks. The administration of olive total and free phenolic compounds at 400 and 800 ppm did not cause any significant changes on ALT and AST activities and serum total lipids. These compounds at 1600 ppm caused significant increase in ALT and AST activities and the content of total lipids. Both olive phenolic compounds were superior to that of BHT in increasing HDL-cholesterol level. Nutritional experiments demonstrated that BHT at 200 ppm caused an enlargement in the kidney and liver of the rat compared with the administration of total and free olive phenolic compounds at 1200 and 1600 ppm. Microscopical examination of kidney and liver tissues of rats administered free and total phenolic compounds at 1200 ppm had the same histological character as that of control rats, while the administration of BHT (200 ppm) and phenolic compounds (1600 ppm) induced severe damage to the tissues of the rat kidney and liver.

Effects of Phos-Chek G75-F and Silv-Ex on developing northern bobwhite quail (Colinus virginianus).

Eggs of nesting birds situated in peripheral areas serving as fire breaks are at risk of being sprayed with fire control chemicals. Acute toxicity tests were conducted by immersing northern bobwhite quail eggs for 10 s in different water-based concentrations of Silv-Ex(R) (SE), a foam-suppressant chemical, and Phos-Chek(R) G75-F (PC), a fire retardant chemical, on day 4 or day 11 of incubation. An attempt was made to relate the treatment concentrations to the actual field application levels. Mortality appeared higher in most groups exposed on day 11 than on day 4, suggesting that on day 11 the extensive chorioallantoic vascular network permitted greater uptake of chemical. Only 24-60% of the embryos survived to hatch at exposure concentrations of 202, 269, and 454 g/L PC when treated on incubation day 11. At higher concentrations including 681956, and 1211 g/L PC, the compound did not completely dissolve in water and clumped on eggshells, resulting in greater hatching success. Exposures to SE at 100 g/L on incubation day 11 did not significantly affect hatching success of embryos but did significantly reduce the percent hematocrit in blood compared with controls. Incubation day 11 exposure to 202 and 1211 g/L PC led to a significant increase in plasma aspartate aminotransferase, and day 4 exposure to 1211 g/L PC resulted in a significant increase in alanine aminotransferase. In addition to elevated liver enzymes, these treatments resulted in a decrease in the number of hepatocyte profiles (1211 g/L PC at day 4 and day 11) and an increase in hepatocyte size (202 and 1211 g/L PC at day 11) in hatchlings. A combination of SE and PC was synergistic (202 g/L PC and 50 g/L SE) at day 11 of incubation with respect to decreased hatching success and reduced bone lengths. However, lower concentrations of SE (10 g/L or 30 g/L) combined with 202 g/L of PC appeared antagonistic. This may be due to SE, as a surfactant, altering the ability of PC to penetrate the egg. Our results show fewer adverse effects following exposure to SE than to PC; therefore application of SE may be less harmful to breeding bird populations.

Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure

Bacterial endotoxin [lipopolysaccharide (LPS)] causes liver injury in vivo that is dependent on platelets, neutrophils [polymorphonuclear leukocytes (PMNs)], and several inflammatory mediators, including thrombin. We tested the hypothesis that thrombin contributes to LPS-induced hepatocellular injury through direct interactions with platelets and/or PMNs in vitro. Perfusion of isolated livers from LPS-treated rats with buffer containing thrombin resulted in a significant increase in alanine aminotransferase (ALT) activity in the perfusion medium, indicating hepatocellular damage. This effect was completely abolished by prior depletion of PMNs from the LPS-treated donor rats but not by depletion of platelets, suggesting interaction between thrombin and PMNs in the pathogenesis. Thrombin did not, however, enhance degranulation of rat PMNs in vitro, and it was not directly toxic to isolated rat hepatocytes in the presence of PMNs even after LPS exposure, suggesting that hepatocellular killing by the PMN-thrombin combination requires the intervention of an additional factor(s) within the liver. In livers from naive donors perfused with buffer containing PMNs and LPS, no injury occurred in the absence of thrombin. Addition of thrombin (10 nM) to the medium caused pronounced ALT release. These results indicate that thrombin and PMNs are sufficient extrahepatic requirements for LPS-induced hepatocellular damage in intact liver.

Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia

Rosuvastatin is a new, synthetic, orally active statin, with marked low-density lipoprotein (LDL) cholesterol-lowering activity. We conducted 2 dose-ranging studies. In the first study, after a 6-week dietary run-in, 142 moderately hypercholesterolemic patients were randomized equally to receive double-blind placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10 or 80 mg once daily for 6 weeks; in the second study, conducted to extend the rosuvastatin dose range, 64 patients were randomized to double-blind, once-daily placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for 6 weeks. Data from both studies were combined for analysis of lipid effects. No statistical comparison of atorvastatin arms with placebo or rosuvastatin was performed. Rosuvastatin was associated with highly significant dose-dependent reductions in LDL cholesterol compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80 mg). Linear regression analysis indicated an additional 4.5% LDL cholesterol reduction for each doubling of the rosuvastatin dose. Across the dose range, approximately 90% of LDL cholesterol reduction occurred within the first 2 weeks of treatment. Significant, dose-dependent reductions in total cholesterol and apolipoprotein B with rosuvastatin were also observed (p <0.001). High-density lipoprotein cholesterol increases and triglyceride reductions were consistently observed and statistically significant at some dose levels. All lipid ratios were significantly reduced at all rosuvastatin dose levels (p <0.001). Adverse events were similar across placebo and active treatments. No significant increases in alanine aminotransferase or creatine kinase were seen in any patient. Over 6 weeks, rosuvastatin produced large, rapid, dose-dependent LDL cholesterol reductions and was well tolerated in hypercholesterolemic patients.

Changes in Liver Function Tests after Laparoscopic Cholecystectomy: Not So Rare, Not Always Ominous

The incidental findings of increased alanine aminotransferase (ALT) and aspartate amino transferase (AST) after uneventful laparoscopic cholecystectomy (LC) prompted us to investigate the incidence and the clinical significance of this phenomenon. Changes in liver function test after LC (n = 55) were compared with those after OC (n = 16). Liver function tests were obtained preoperatively and postoperatively on days 1, 2, and 7. All of the patients fulfilled the selection criteria: normal preoperative liver function test and no endoscopic retrograde cholangiopancreatography, common bile duct exploration, or postoperative biliary complications (injury, infection, or obstruction). Converted cholecystectomies were also excluded. During LC, the intra-abdominal pressure was maintained within the conventional range of 14 to 15 mm Hg. ALT had doubled in the first 48 hours from the preoperative mean in 58.2 per cent in LC patients versus only 6.3 per cent in the OC group. AST doubled from the preoperative mean value in 38.2 per cent in the LC group versus only 6.3 per cent in the OC group. By the 7th postoperative day, the enzymes returned to the preoperative values in both the LC and the OC group. In many instances, a significant increase in ALT and AST blood levels occurred after uneventful LC. The phenomenon is transient as these enzymes returned to normal value within 7 days. These changes are clinically silent in patients with a normal liver function.