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Development and validation of a novel non-invasive test for diagnosing fibrotic non-alcoholic steatohepatitis in patients with biopsy-proven non-alcoholic fatty liver disease

Gao F, Huang JF, Zheng KI, Pan XY, Ma HL, Liu WY, et al.

J Gastroenterol Hepatol, 2020 Oct;35(10):1804-1812.
PMID: 32246876 DOI: 10.1111/jgh.15055

BACKGROUND AND AIM: There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH.
METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.
RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes

Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA

J Toxicol, 2009;2009:912320.
PMID: 20130764 DOI: 10.1155/2009/912320

Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.

Matched MeSH terms: Aspartate Aminotransferases
The effects of orthodontic forces during canine retraction using self-ligating brackets on gingival crevicular fluid enzyme activity, canine movement and root resorption

Rohaya Megat Abdul Wahab*, Albira Sintian, Zulham Yamamoto, Nurfathiha Abu Kasim, Intan Zarina Zainol Abidin, Sahidan Senafi, et al.

Sains Malaysiana, 2015;44:249-256.

Alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and aspartate aminotransferase (AST) activities were studied as biomarkers of canine movement. Root resorption was also evaluated in canines subjected to the orthodontic forces. Nineteen subjects randomly received 100 and 150 g force using self-ligating brackets (SLB) either on the right or left site of maxillary arch. Gingival crevicular fluid samples were collected at distal sites of canines for five consecutive weeks. The activities of ALP, TRAP and AST were assayed and measured spectrophotometrically. Canine movement was measured for five consecutive weeks while root resorption was monitored at baseline, week 0 and week 5 using periapical radiographs. In 100 g group, TRAP activity significantly increased in week 3-5 when compared to TRAP baseline activity. However, ALP and AST activities slightly increased. In 150 g group, ALP and TRAP activities slightly increased when compared with their baseline activities. However, AST significantly increased in week 5. Canine movement and root resorption were not significantly different (p<0.05) in both groups. A force of 100 and 150 g slightly increased the bone modeling process and resulted in similar canine movement and root resorption. Therefore, 100 g force could be an optimum force for canine retraction and is preferable (compared with 150 g force) in canine retraction using SLB.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial

Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, et al.

Nutr J, 2013;12(1):166.
PMID: 24373555 DOI: 10.1186/1475-2891-12-166

Nonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.

Matched MeSH terms: Aspartate Aminotransferases/blood
Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study

Verma N, Duseja A, Mehta M, De A, Lin H, Wong VW, et al.

Aliment Pharmacol Ther, 2024 Mar;59(6):774-788.
PMID: 38303507 DOI: 10.1111/apt.17891

BACKGROUND: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD).
AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients.
METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria).
RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set).
CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.

Matched MeSH terms: Aspartate Aminotransferases
Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats

Akowuah GA, Zhari I, Mariam A, Yam MF

Food Chem Toxicol, 2009 Sep;47(9):2321-6.
PMID: 19540299 DOI: 10.1016/j.fct.2009.06.022

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42+/-0.09 microg/ml and 1.31+/-0.04 microg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p>0.05) in plasma total antioxidant status (TAS) as compare to values of control group.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats

Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, et al.

Nutrients, 2017 Jul 18;9(7).
PMID: 28718838 DOI: 10.3390/nu9070766

Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.

Matched MeSH terms: Aspartate Aminotransferases/blood
Diagnosis of Fibrosis Using Blood Markers and Logistic Regression in Southeast Asian Patients With Non-alcoholic Fatty Liver Disease

Sang C, Yan H, Chan WK, Zhu X, Sun T, Chang X, et al.

Front Med (Lausanne), 2021;8:637652.
PMID: 33708783 DOI: 10.3389/fmed.2021.637652

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India (n1 = 540, n2 = 147, and n3 = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.

Matched MeSH terms: Aspartate Aminotransferases
In vivo study of human Plasmodium knowlesi in Macaca fascicularis

Anderios F, Noorrain A, Vythilingam I

Exp Parasitol, 2010 Feb;124(2):181-9.
PMID: 19765587 DOI: 10.1016/j.exppara.2009.09.009

Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious to humans. In this study Macaca fascicularis was used as a model to understand the host response to P. knowlesi using parasitological and haematological parameters. Three M. fascicularis of either sex were experimentally infected with P. knowlesi erythrocytic parasites from humans. The pre-patent period for P. knowlesi infection in M. fascicularis ranged from seven to 14 days. The parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual stage and 88-264 parasites per microL of blood for sexual stage. Periodicity analysis adopted from microfilaria periodicity technique of asexual stage showed that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h. Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to display periodicity with a peak (24:00-06:00) that coincides with the peak biting activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late trophozoite. However, it may be distinguishable by observing the appliqué appearance of the cytoplasm and the chromatin lying inside the ring. Haematological analysis on macaques with knowlesi malaria showed clinical manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross examination of spleen and liver showed malaria pigments deposition in both organs.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: the GOASIA study

Pitisuttithum P, Chan WK, Piyachaturawat P, Imajo K, Nakajima A, Seki Y, et al.

BMC Gastroenterol, 2020 Apr 06;20(1):88.
PMID: 32252638 DOI: 10.1186/s12876-020-01240-z

BACKGROUND: The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly population.
METHODS: We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis.
RESULTS: Of the 1008 patients, 175 were elderly [age 64 (62-67) years], who were matched with 525 non-elderly patients [46 (36-54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p

Matched MeSH terms: Aspartate Aminotransferases
The value of liver function tests in hepatocellular carcinoma

Lopez JB, Balasegaram M, Thambyrajah V, Timor J

Malays J Pathol, 1996 Dec;18(2):95-9.
PMID: 10879229

This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Prevalence and incidence of liver dysfunction and assessment of biomarkers of liver disease in HIV-infected Asian children

Aurpibul L, Bunupuradah T, Sophan S, Boettiger D, Wati DK, Nguyen LV, et al.

Pediatr Infect Dis J, 2015 Jun;34(6):e153-8.
PMID: 25970117 DOI: 10.1097/INF.0000000000000693

We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Effects of nerol on paracetamol-induced liver damage in Wistar albino rats

Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, et al.

Biomed Pharmacother, 2021 Aug;140:111732.
PMID: 34130201 DOI: 10.1016/j.biopha.2021.111732

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

Matched MeSH terms: Aspartate Aminotransferases/blood
Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients

Ahmad A, Waseem T, Butt NF, Randhawa FA, Malik U, Shakoori TA

Trop Biomed, 2018 Dec 01;35(4):1115-1122.
PMID: 33601858

A significant percentage of dengue patients develop Dengue Shock Syndrome (DSS) which is characterized by increased vascular permeability, circulatory failure and often death. Montelukast, a cysteinyl leukotriene receptor antagonist regulates vascular permeability and we hypothesized that it may be effective in protecting against DSS. An open label, parallel, randomized controlled trial (RCT) was thus carried out at Mayo Hospital, Department of Medicine, Lahore. A total of 200 patients of dengue fever were recruited and randomized into two groups. The group A was treated with Montelukast 10 mg once daily for 5 days along with general supportive treatment. Group B received the standard supportive treatment and served as the control group. The frequency of DSS was compared in the two groups by Chi square test. A binary logistic regression analysis was conducted to assess the effects of montelukast treatment on onset of DSS after adjusting for gender, age, white cell count, platelet count, haematocrit, serum alanine transaminase (ALT) and aspartate transaminase (AST). Relative risk (RR), absolute risk reduction (ARR), relative risk reduction (RRR) and numbers needed to treat (NNT) were calculated. Significance level was set at p0.001, Odds ratio=5.01, 95% CI=2.17-11.60) even after adjusting for confounders. Montelukast reduced the absolute risk (ARR=22%) and the relative risk (RRR=71%) of DSS in dengue fever. Numbers needed to treat were 4.55. We thus conclude that treatment with oral montelukast may protect patients of dengue fever from DSS and greatly reduce mortality.

Matched MeSH terms: Aspartate Aminotransferases
Potential protective effect of sunitinib after administration of diclofenac: biochemical and histopathological drug-drug interaction assessment in a mouse model

Tan JR, Chakravarthi S, Judson JP, Haleagrahara N, Segarra I

Naunyn Schmiedebergs Arch Pharmacol, 2013 Jul;386(7):619-33.
PMID: 23552887 DOI: 10.1007/s00210-013-0861-4

Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Protective effect of the ethanol extract of Zingiber officinale Roscoe on paracetamol induced hepatotoxicity in rats

Norina Abdullah, Nur Zakiah Mohd Saat, Hazlin Abu Hasan, Siti Balkis Budin, Sazlina Kamaralzaman

Jurnal Sains Kesihatan Malaysia, 2004;2(2):85-95.
MyJurnal

The protective effect of the ethanol extract of the rhizome of Zingiber officinale Roscoe on acute hepatotoxicity induced by paracetamol (1000 mg/kg) was studied in plasma and hepatic tissue samples obtained from male Sprague-Dawley rats. The ethanol extract was given in oral doses of 200 mg/kg and 300 mg/kg to the rats at 0, 4 and 8 hrs after paracetamol was given orally. The plasma and liver of the rats were subjected to biochemical analysis 24 hrs after hepatotoxicity was induced to determine the levels of superoxide dismutase(SOD), malonaldehyde (MDA) and aspartate transaminase (AST). The results were compared to the rats which were given the antidote N-acetylcysteine (NAC) (500 mg/kg) at 0, 4 and 8 hrs after the paracetamol dose. The results showed that at 200 mg/kg the extract reduced the plasma levels of SOD significantly (p < 0.05) while at a higher dose of 300 mg/kg it reduced plasma SOD, hepatic MDA, serum AST and increased the levels of plasma proteins significantly (p < 0.05). In conclusion, the ethanol extract of Z. officinale showed protective effect against paracetamol induced hepatotoxicity at both dose levels and the protective effect was better at the higher dose.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Evaluation of the hepatoprotective Effects of Lantadene A, a pentacyclic triterpenoid of Lantana plants against acetaminophen-induced liver damage

Grace-Lynn C, Chen Y, Latha LY, Kanwar JR, Jothy SL, Vijayarathna S, et al.

Molecules, 2012 Nov 23;17(12):13937-47.
PMID: 23178309 DOI: 10.3390/molecules171213937

The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg) showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05). Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.

Matched MeSH terms: Aspartate Aminotransferases/metabolism
Reconstruction of the transcriptional regulatory network in arabidopsis thaliana aliphatic glucosinolate biosynthetic pathway

Khalidah-Syahirah Ashari, Zeti-Azura Mohamed-Hussein, Muhammad-Redha Abdullah-Zawawi, Sarahani Harun

Sains Malaysiana, 2018;47:2993-3002.

Aliphatic glucosinolate is an important secondary metabolite responsible in plant defense mechanism and carcinogenic
activity. It plays a crucial role in plant adaptation towards changes in the environment such as salinity and drought.
However, in many plant genomes, there are thousands of genes encoding proteins still with putative functions and
incomplete annotations. Therefore, the genome of Arabidopsis thaliana was selected to be investigated further to identify
any putative genes that are potentially involved in the aliphatic glucosinolate biosynthesis pathway, most of its gene are
with incomplete annotation. Known genes for aliphatic glucosinolates were retrieved from KEGG and AraCyc databases.
Three co-expression databases i.e., ATTED-II, GeneMANIA and STRING were used to perform the co-expression network
analysis. The integrated co-expression network was then being clustered, annotated and visualized using Cytoscape plugin,
MCODE and ClueGO. Then, the regulatory network of A. thaliana from AtRegNet was mapped onto the co-expression
network to build the transcriptional regulatory network. This study showed that a total of 506 genes were co-expressed
with the 61 aliphatic glucosinolate biosynthesis genes. Five transcription factors have been predicted to be involved
in the biosynthetic pathway of aliphatic glucosinolate, namely SEPALLATA 3 (SEP3), PHYTOCHROME INTERACTING FACTOR
3-like 5 (AtbHLH15/PIL5), ELONGATED HYPOCOTYL 5 (HY5), AGAMOUS-like 15 (AGL15) and GLABRA 3 (GL3). Meanwhile,
three other genes with high potential to be involved in the aliphatic glucosinolates biosynthetic pathway were identified,
i.e., methylthioalkylmalate-like synthase 4 (MAML-4) and aspartate aminotransferase (ASP1 and ASP4). These findings
can be used to complete the aliphatic glucosinolate biosynthetic pathway in A. thaliana and to update the information
on the glucosinolate-related pathways in public metabolic databases.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Toxicity study of Orthosiphon stamineus Benth (Misai Kucing) on Sprague Dawley rats

Chin JH, Abas HH, Sabariah I

Trop Biomed, 2008 Apr;25(1):9-16.
PMID: 18600199

Orthosiphon stamineus Benth (Family: Lamiaceae) or locally known as Misai Kucing has been widely used in Malaysia for treating kidney problems, gout, and diabetes. This study aims to evaluate the possible toxic effect after following fourteen days oral administration of methanol extract of O. stamineus in female Sprague Dawley (SD) rats. Control groups were treated orally with distilled water (vehicle) while the four test groups were treated up to fourteen days with 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight of methanol extract of O. stamineus respectively. Toxicity of the methanol extract of O. stamineus was evaluated by the incident of lethality, side-cage observation and blood serum biochemical parameters. No lethality or adverse toxic signs were seen during the experimental period. A significant decrease in several serum biochemical parameters i.e. AST and ALT and increase in liver weight was observed in young female SD rat after being fed fourteen days with methanol extract of O. stamineus. No delayed toxic effect and lethality was observed in all rats during fourteen days of recovery period. In conclusion, methanol extract of O. stamineus within these range and treatment duration would not cause any severe toxic effects and organ damages in rats.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Brewers' Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats

Tan BL, Norhaizan ME, Hairuszah I, Hazilawati H, Roselina K

Oxid Med Cell Longev, 2015;2015:539798.
PMID: 26257841 DOI: 10.1155/2015/539798

Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease.

Matched MeSH terms: Aspartate Aminotransferases/blood

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