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Fulltext Validation of the Blood Test MACK-3 for the Noninvasive Diagnosis of Fibrotic Nonalcoholic Steatohepatitis: An International Study With 1924 Patients

Canivet CM, Zheng MH, Qadri S, Vonghia L, Chuah KH, Costentin C, et al.

Clin Gastroenterol Hepatol, 2023 Nov;21(12):3097-3106.e10.
PMID: 37031715 DOI: 10.1016/j.cgh.2023.03.032

BACKGROUND & AIMS: Drug development in nonalcoholic steatohepatitis (NASH) is hampered by a high screening failure rate that reaches 60% to 80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including 3 biomarkers (aspartate aminotransferase, homeostasis model assessment, and cytokeratin 18), recently was developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study.
METHODS: A total of 1924 patients with biopsy-proven nonalcoholic fatty liver disease from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all patients. FibroScan-aspartate aminotransferase score (FAST), an elastography-based test for fibrotic NASH, also was available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with a Nonalcoholic Fatty Liver Disease Activity Score of 4 or higher and fibrosis stage of F2 or higher according to the NASH Clinical Research Network scoring system.
RESULTS: The area under the receiver operating characteristic of MACK-3 for fibrotic NASH was 0.791 (95% CI 0.768-0.814). Sensitivity at the previously published MACK-3 threshold of less than 0.135 was 91% and specificity at a greater than 0.549 threshold was 85%. The MACK-3 area under the receiver operating characteristic was not affected by age, sex, diabetes, or body mass index. MACK-3 and FAST results were well correlated (Spearman correlation coefficient, 0.781; P < .001). Except for an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate).
CONCLUSIONS: The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients

Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.

JGH Open, 2020 Dec;4(6):1155-1161.
PMID: 33319051 DOI: 10.1002/jgh3.12414

Background and Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.
Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.
Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score

Matched MeSH terms: Aspartate Aminotransferases
Treatment of subperiodic Brugia malayi infection with a single dose of ivermectin

Mak JW, Navaratnam V, Grewel JS, Mansor SM, Ambu S

Am J Trop Med Hyg, 1993 Apr;48(4):591-6.
PMID: 8480868

A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Transient hyperthyroidism of hyperemesis gravidarum

Tan JYL, Loh KC, Yeo GSH, Chee YC

BJOG, 2002 Jun;109(6):683-8.
PMID: 12118648

OBJECTIVE: To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum.
DESIGN: Prospective observational study.
SETTING: Hospital inpatient gynaecological ward.
POPULATION: Women admitted with hyperemesis gravidarum and found to have hyperthyroidism.
METHODS: Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation.
MAIN OUTCOME MEASURES: Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes).
RESULTS: Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile.
CONCLUSIONS: In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

Matched MeSH terms: Aspartate Aminotransferases/metabolism
Toxicological evaluation of 80% methanol extract of Ludwigia octovalvis (Jacq.) P.H. Raven leaves (Onagraceae) in BALB/c mice

Kadum Yakob H, Manaf Uyub A, Fariza Sulaiman S

J Ethnopharmacol, 2012 Aug 1;142(3):663-8.
PMID: 22705121 DOI: 10.1016/j.jep.2012.05.035

Ludwigia octovalvis (Jacq.) P. H. Raven (Family: Onagraceae), as a traditional Malay herbal medicine,has been used to treat gastrointestinal complaints such as diarrhea and dysentery.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext Toxicological Features of Catha edulis (Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

Alsalahi A, Abdulla MA, Al-Mamary M, Noordin MI, Abdelwahab SI, Alabsi AM, et al.

Evid Based Complement Alternat Med, 2012;2012:829401.
PMID: 23259000 DOI: 10.1155/2012/829401

Hepato- and nephrotoxicity of Khat consumption (Catha edulis Forskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100-120 g) were distributed randomly into four groups of males and female (n = 12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract of Catha edulis orally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

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 Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar F, Saleem U, Rehman AU, Ahmad B, Froeyen M, Mirza MU, et al.

Front Pharmacol, 2021;12:607026.
PMID: 34040515 DOI: 10.3389/fphar.2021.607026

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD
50
. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

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
Fulltext Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

Abu MN, Samat S, Kamarapani N, Nor Hussein F, Wan Ismail WI, Hassan HF

Evid Based Complement Alternat Med, 2015;2015:985042.
PMID: 25821506 DOI: 10.1155/2015/985042

The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

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
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
The effect of tocotrienol-rich fraction on oxidative liver damage induced by fenitrothion

Putri Ayu Jayusman, Siti Balkis Budin, Putri Ayu Jayusman SBB, Izatus Shima Taib, Ahmad Rohi Ghazali

Sains Malaysiana, 2017;46:1603-1609.

Exposure to organophosphate pesticide including fenitrothion (FNT) has led to many adverse effects on human health.
However, a potent antioxidant like palm oil tocotrienol-rich fraction (TRF) can reduce oxidative damage in various
pathological conditions, could also reduce the adverse effects by FNT. The aim of this study was to evaluate the effect
of TRF on oxidative liver damage in FNT induce hepatotoxicity in experimental rats. A total of 40 male Sprague-Dawley
rats were randomly divided into four groups of 10, namely control, TRF, FNT and TRF+FNT group. TRF (200 mg/kg
body weight) and FNT (20 m/kg body weight) were administered through oral gavage for 28 days. Corn oil which
served as vehicle was given orally to the control group. At the end of the study period, liver and blood was taken for
oxidative damage and biochemical evaluation and histological observation. TRF supplementation prevents oxidative
liver damage by reducing the hepatic malondialdehyde (MDA) and protein carbonyl (PCO) level significantly. Besides,
TRF also restored the endogenous antioxidants particularly reduced glutathione (GSH), glutathione peroxidase (GPx)
and ferric reducing/antioxidant power (FRAP). TRF also prevent liver damage by reducing the liver enzymes, alanine
aminotransferase (ALT) and aspartate aminotransferase (AST). The attenuation of liver damage by TRF was also showed
histologically. In conclusion, TRF supplementation showed a potential in preventing oxidative liver damage in FNTtreated
rats by reducing the oxidative damage and improving the antioxidant status.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext The combination of mitragynine and morphine prevents the development of morphine tolerance in mice

Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P

Molecules, 2013 Jan 04;18(1):666-81.
PMID: 23292329 DOI: 10.3390/molecules18010666

Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.

Matched MeSH terms: Aspartate Aminotransferases/metabolism
Fulltext The Safety Of Capsules Containing Lactic Acid Bacilli

Paraidathathu, Thomas, Lee, S.H.

Ann Dent, 1999;6(1):-.
MyJurnal

The population in Malaysia use various types of health and food supplements. These products are considered safe and are used without any concern for their toxicity. Among the products used as health supplements are products that contain lactic acid bacteria. This project studied the acute and subacute toxicity of a product containing minerals, herbs, vitamins and live lactic acid bacteria, on Sprague- Dawley rats. Acute toxicity was tested 24 hours after a single dose and subacute toxicity was studied 24 hours after 7 days of daily dosing. The parameters that were studied were alanine aminotransferase (AL T,SGPT), aspartate aminotransferase (AST, SGOT), serum urea, ratios of weight of kidney and liver weight to body weight and percentage changes in body weights. The contents of capsules of the product (6, 8 or lO capsules for acute studies and 6, 10 and 12 for subacute studies) were mixed with corn oil and fed orally to rats. Control rats were fed with corn oil alone. In the acute studies, the level of ALT in the rats treated with the contents of the capsule was lower than controls. There were no significant changes in the other parameters of the rats in the treatment groups as compared to controls. There were no significant differences in all the parameters between rats in the treatment groups as compared to controls in the subacute studies. Sprague-Dawley rats fed with high doses of the product did not show signs of toxicity in the parameters that were studied.

Matched MeSH terms: Aspartate Aminotransferases
The Kinetics of Enzyme Mixtures

Brown S, Muhamad N, C Pedley K, C Simcock D

Mol Biol Res Commun, 2014 Mar;3(1):21-32.
PMID: 27843974

Even purified enzyme preparations are often heterogeneous. For example, preparations of aspartate aminotransferase or cytochrome oxidase can consist of several different forms of the enzyme. For this reason we consider how different the kinetics of the reactions catalysed by a mixture of forms of an enzyme must be to provide some indication of the characteristics of the species present. Based on the standard Michaelis-Menten model, we show that if the Michaelis constants (Km) of two isoforms differ by a factor of at least 20 the steady-state kinetics can be used to characterise the mixture. However, even if heterogeneity is reflected in the kinetic data, the proportions of the different forms of the enzyme cannot be estimated from the kinetic data alone. Consequently, the heterogeneity of enzyme preparations is rarely reflected in measurements of their steady-state kinetics unless the species present have significantly different kinetic properties. This has two implications: (1) it is difficult, but not impossible, to detect molecular heterogeneity using kinetic data and (2) even when it is possible, a considerable quantity of high quality data is required.

Matched MeSH terms: Aspartate Aminotransferases
The Hepatoprotective Effect of Clidemia hirta against Carbon Tetrachloride (CCl4)-Induced Oxidative Stress and Hepatic Damage in Mice

Amzar N, Iqbal M

J Environ Pathol Toxicol Oncol, 2017;36(4):293-307.
PMID: 29431062 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019824

Liver diseases still represents a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases, including liver disease. Clidemia hirta possesses many medicinal properties for healing several diseases and for health maintenance. However, the hepatoprotective effects and antioxidative potential of C. hirta have not been fully investigated. In the present study, we evaluated the hepatoprotective and antioxidative potential of C. hirta against carbon tetrachloride (CCl4)-induced liver injuries and oxidative damage in a murine model. Various biochemical changes associated with liver damage and oxidative stress were measured. The mice were pretreated for 14 consecutive days with aqueous extract of C. hirta at selected doses (150 mg/kg body weight [b.w.], 300 mg/kg b.w. and 600 mg/kg b.w.) followed by two doses of CCl4 (1.0 mL/kg b.w.) orally on days 14 and 15. All animals were sacrificed 24 hours after the last dose of CCl4 or saline. Blood and liver tissues were taken quickly for biochemical and histopathological studies to assess the derangement in the functioning of liver. The development of oxidative stress was observed through the escalation of hepatic lipid peroxidation, depletion of glutathione, and reduced antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, glutathione S-transferase and quinone reductase). Hepatic damage was evaluated by measuring serum transaminase (ALT and AST). In addition, CCl4-induced hepatic damage was further evaluated using histopathological assessments. However, most of these changes were dependently ameliorated by the pretreatment of mice with a C. hirta dose. These results indicate that the hepatoprotective effect of C. hirta might be due to its antioxidant and free-radical scavenging properties.

Matched MeSH terms: Aspartate Aminotransferases/blood
Fulltext The Effect of Amygdalin on Endoplasmic Reticulum (ER) Stress Induced Hepatic Steatosis in Mice

Moslehi A, Farahabadi M, Chavoshzadeh SA, Barati A, Ababzadeh S, Mohammadbeigi A

Malays J Med Sci, 2018 Feb;25(1):16-23.
PMID: 29599631 DOI: 10.21315/mjms2018.25.1.3

Background: Endoplasmic reticulum (ER) stress creates abnormalities in the insulin action, inflammatory responses, lipoprotein B100 degradation, and hepatic lipogenesis. Hepatic steatosis leads to a broad spectrum of hepatic disorders such as nonalcoholic fatty liver disease (NAFLD) and NASH. Amygdalin has beneficial effects on asthma, bronchitis, diabetes, and atherosclerosis. We designed this study to evaluate the effect of amygdalin on the ER stress induced hepatic steatosis.
Methods: Inbred mice received saline, DMSO and amygdalin, as control groups. ER stress was induced by tunicamycin (TM) injection. Amygdalin was administered 1 h before the TM challenge (Amy + TM group). Mice body and liver weights were measured. Hematoxylin and eosin (H&E) and oil red O staining from liver tissue, were performed. Alanin aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride and cholesterol levels were measured.
Results: Histological evaluation revealed that amygdalin was unable to decrease the TM induced liver steatosis; however, ALT and AST levels decreased [ALT: 35.33(2.15) U/L versus 92.33(6.66) U/L; (57.000, (50.63, 63.36),P< 0.001) and AST: 93(5.09) U/L versus 345(97.3) U/L, (252, (163.37, 340.62),P< 0.001)]. Amygdalin also decreased triglyceride and cholesterol plasma levels in the Amy + TM group [TG: 42.66(2.15) versus 53.33(7.24) mg/dL; (10.67, (3.80, 17.54),P= 0.006) and TC: 9.33(3.55) versus 112.66(4.31) mg/dL, (103.33, (98.25, 108.40)P< 0.001)].
Conclusion: Amygdalin improved the ALT, AST, and lipid serum levels after the TM challenge; however, it could not attenuate hepatic steatosis.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Swietenine potentiates the antihyperglycemic and antioxidant activity of Metformin in Streptozotocin induced diabetic rats

Shiming Z, Mak KK, Balijepalli MK, Chakravarthi S, Pichika MR

Biomed Pharmacother, 2021 Jul;139:111576.
PMID: 33862494 DOI: 10.1016/j.biopha.2021.111576

Diabetes mellitus or type-2 diabetes, commonly referred as diabetes, is a metabolic disorder that results in high blood sugar level. Despite the availability of several antidiabetic drugs in the market, they still do not adequately regulate blood sugar levels. Thus, in general people prefer to use herbal supplements/medicines along with antidiabetic drugs to control blood sugar levels. One of such herbal medicine is Swietenia macrophylla seeds. It is widely used in Asia for controlling blood sugar levels. One of the major bioactive compounds, Swietenine, is reported to be responsible for controlling blood glucose levels. However, there were no studies on its efficacy in controlling the blood glucose in diabetic rats. In this study, we evaluated the antihyperglycemic activity of Swietenine and its pharmacodynamic interaction with Metformin in Streptozotocin induced diabetes in rats. The activity of Swietenine was investigated at three different doses: 10, 20 and 40 mg/kg body weight (bw). Metformin (50 mg/kg bw) was used as a standard drug. Swietenine (20 and 40 mg/kg bw) and Metformin (50 mg/kg bw) showed significant effect in reducing the glucose, cholesterol, triglycerides, low-density lipoprotein, urea, creatinine, alanine transaminase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and malondialdehyde level in serum while it had increased the high-density lipoprotein, glutathione, and total antioxidant capacity level. In addition, Swietenine (20 and 40 mg/kg) had shown significant synergistic effect with Metformin. Administration of Swietenine at 10 mg/kg bw neither showed activity nor influenced Metformin's activity. The results from this study confirmed the beneficial effects of Swietenine and its synergistic action with Metformin in controlling the dysregulated serum parameters in Streptozotocin induced diabetes in rats.

Matched MeSH terms: Aspartate Aminotransferases
Fulltext Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

Afroz R, Tanvir EM, Karim N, Hossain MS, Alam N, Gan SH, et al.

Biomed Res Int, 2016;2016:6437641.
PMID: 27294126 DOI: 10.1155/2016/6437641

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.

Matched MeSH terms: Aspartate Aminotransferases/metabolism

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