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Induction of Chronic Subclinical Systemic Inflammation in Sprague-Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide

Ranneh Y, Akim AM, Hamid HA, Khazaai H, Mokhtarrudin N, Fadel A, et al.

Arch Immunol Ther Exp (Warsz), 2019 Dec;67(6):385-400.
PMID: 31278602 DOI: 10.1007/s00005-019-00553-6

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P

Matched MeSH terms: Alanine Transaminase/metabolism
Fulltext Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific

Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.

HIV Med, 2020 07;21(6):397-402.
PMID: 31852025 DOI: 10.1111/hiv.12836

OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.
METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.
RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) 100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.
CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

Matched MeSH terms: Alanine Transaminase/metabolism
Antioxidant activity of white rice, brown rice and germinated brown rice (in vivo and in vitro) and the effects on lipid peroxidation and liver enzymes in hyperlipidaemic rabbits

Mohd Esa N, Abdul Kadir KK, Amom Z, Azlan A

Food Chem, 2013 Nov 15;141(2):1306-12.
PMID: 23790918 DOI: 10.1016/j.foodchem.2013.03.086

Antioxidant activity of different rice extract and the effect on the levels of antioxidant enzyme activity, superoxide dismutase (SOD) and glutathione peroxidase (GPx), vitamin E, lipid peroxidation and liver enzymes in hyperlipidaemia rabbits were investigated. Germinated brown rice (GBR) has the highest antioxidant activity compared to white rice (WR) and brown rice (BR). All rice grains increased the activity of SOD and GPx. However, vitamin E levels increased only in the groups that received the BR and GBR diets. The reduction of lipid peroxidation levels and activity of hepatic enzymes (alanine transferase, ALT and aspartate transaminase, AST) were only significantly observed in the GBR group. In conclusion, GBR supplementation has the greatest impact on increasing antioxidant enzyme activity and vitamin E level and on reducing lipid peroxidation in hypercholesterolaemia rabbit, thereby preventing the formation of atherosclerotic plaques. Furthermore, GBR diet can also reduce the level of hepatic enzymes.

Matched MeSH terms: Alanine Transaminase/metabolism
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: Alanine Transaminase/metabolism
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: Alanine Transaminase/metabolism
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: Alanine Transaminase/metabolism
Fulltext Effects of white rice, brown rice and germinated brown rice on antioxidant status of type 2 diabetic rats

Imam MU, Musa SN, Azmi NH, Ismail M

Int J Mol Sci, 2012;13(10):12952-69.
PMID: 23202932 DOI: 10.3390/ijms131012952

Oxidative stress is implicated in the pathogenesis of diabetic complications, and can be increased by diet like white rice (WR). Though brown rice (BR) and germinated brown rice (GBR) have high antioxidant potentials as a result of their bioactive compounds, reports of their effects on oxidative stress-related conditions such as type 2 diabetes are lacking. We hypothesized therefore that if BR and GBR were to improve antioxidant status, they would be better for rice consuming populations instead of the commonly consumed WR that is known to promote oxidative stress. This will then provide further reasons why less consumption of WR should be encouraged. We studied the effects of GBR on antioxidant status in type 2 diabetic rats, induced using a high-fat diet and streptozotocin injection, and also evaluated the effects of WR, BR and GBR on catalase and superoxide dismutase genes. As dietary components, BR and GBR improved glycemia and kidney hydroxyl radical scavenging activities, and prevented the deterioration of total antioxidant status in type 2 diabetic rats. Similarly, GBR preserved liver enzymes, as well as serum creatinine. There seem to be evidence that upregulation of superoxide dismutase gene may likely be an underlying mechanism for antioxidant effects of BR and GBR. Our results provide insight into the effects of different rice types on antioxidant status in type 2 diabetes. The results also suggest that WR consumption, contrary to BR and GBR, may worsen antioxidant status that may lead to more damage by free radicals. From the data so far, the antioxidant effects of BR and GBR are worth studying further especially on a long term to determine their effects on development of oxidative stress-related problems, which WR consumption predisposes to.

Matched MeSH terms: Alanine Transaminase/metabolism
Prospective association of liver function biomarkers with development of hepatobiliary cancers

Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.

Cancer Epidemiol, 2016 Feb;40:179-87.
PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002

INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.
METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).
RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).
CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

Matched MeSH terms: Alanine Transaminase/metabolism
Association of raised liver transaminases with physical inactivity, increased waist-hip ratio, and other metabolic morbidities in severely obese children

Lee YS, Kek BL, Poh LK, Saw SM, Loke KY

J Pediatr Gastroenterol Nutr, 2008 Aug;47(2):172-8.
PMID: 18664869 DOI: 10.1097/MPG.0b013e318162a0e5

To identify factors associated with raised alanine transaminase, aspartate transaminase, and gamma-glutaryl transferase in severely obese children

Matched MeSH terms: Alanine Transaminase/metabolism
Hepatoprotective potential of glyceryl trinitrate against chemically induced oxidative stress and hepatic injury in rats

Rahman A, Vasenwala SM, Iqbal M

Hum Exp Toxicol, 2017 Aug;36(8):785-794.
PMID: 27758841 DOI: 10.1177/0960327116665675

Glyceryl trinitrate (GTN) has been used widely as a potent vasodilator to treat heart conditions, such as angina pectoris and chronic heart failure. This study aims to elucidate the effect of exogenous nitric oxide (NO) administration, using GTN, on carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in rats. The results obtained demonstrated that NO generated by the administration of GTN affords protection against CCl4-induced oxidative stress and liver injury. Administration of CCl4resulted in a significant ( p < 0.001) increase in lipid peroxidation and tissue damage markers (aspartate and alanine transaminase and lactate dehydrogenase) release in serum. Parallel to these changes, CCl4also caused downregulation of antioxidant enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), and several fold induction in γ-glutamyl transpeptidase (GGT) activity. Subsequent administration of GTN resulted in significant ( p < 0.001) recovery of GSH-metabolizing enzymes in a dose-dependent manner. Further, administration of NO inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), exacerbated CCl4-induced oxidative tissue injury. Overall, the study suggests that GTN might suppress oxidant-induced tissue injury and hepatotoxicity in rats.

Matched MeSH terms: Alanine Transaminase/metabolism
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: Alanine Transaminase/metabolism

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