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Fulltext Epigenetic changes of DRD2 gene in Pathogenesis of Schizophrenia

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):3-3.
MyJurnal

The dopamine hypothesis has earlier dominated the theories for the
development of schizophrenia based on the early pharmacologic evidence. The
antipsychotic drugs, among others, is thought to interfere with the function of the
dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence
suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia.
Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is
insufficient mainly due to the poor accessibility and limited brain samples. Of late, new
data has suggested the global impact of DNA methylation in the development of
schizophrenia, thus methylation in the peripheral blood could infer changes in the brain.
The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of
schizophrenia.
Fulltext Prediction of clinical symptoms of Schizophrenia based on COMT Methylation marker

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):19-19.
MyJurnal

The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic
state is involved in causing psychosis and antipsychotic drugs block the
dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter
dopamine in the synapses and plays a role in the neurocognitive function. The
dysregulation of dopamine in the prefrontal cortex influences the cognitive function and
the severity of the psychotic symptoms in schizophrenia. During epigenetic event,
methylated COMT gene may cause reduction in its expression and contribute to the
clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the
feasibility of using COMT DNA methylation for the prediction of specific psychotic
presentation of schizophrenia. (Copied from article).
Fulltext Anti-atherosclerotic effects of Eurycoma Longifolia (Tongkat Ali) in rats fed on High-fat diet

Fakhria Al-Joufi, Anil K. Saxena, Imad M. Al-Ani, Norlelawati A. Talib, Rafidah H. Mokhtar, Norsidah Ku -Zaifah

International Medical Journal Malaysia, 2017;16(1):83-90.
MyJurnal

Atherosclerosis in cardiovascular disease (CVD) is a growing health problem, especially in developing countries. Hyperlipidemia is known as a dominant risk factor for the development of atherosclerosis. This study was designed to investigate the effects of Eurycoma Longifolia (EL) also known as Malaysian Ginseng/ Tongkat Ali on the testosterone level, biochemical changes of lipid profile and intima media thickness (IMT) in rats fed on high-fat diet. Twenty young, adult male Sprague-Dawley (SD) rats were housed for 12 weeks. After one week of acclimatization, they were randomly divided into four groups of 5 animals each and treated for 12 weeks as follow: Group ND was given only normal diet, group NDEL was given normal diet and EL extracts (15mg/kg) dissolved in distilled water, group HFD was given only high fat diet and group HFDEL was given high fat diet and EL extracts (15mg/kg). Rats which were treated with EL (NDEL and HFDEL) showed a significant increase (p
Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet

Norsidah KZ, Asmadi AY, Azizi A, Faizah O, Kamisah Y

J Physiol Biochem, 2013 Sep;69(3):441-9.
PMID: 23208529 DOI: 10.1007/s13105-012-0226-3

Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2-6 were fed 1% methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14 ± 0.33 and 4.30 ± 0.26 vs 5.49 ± 0.25 mmol/L, p < 0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49 ± 3 vs 69 ± 4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p < 0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats' hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.
Fulltext Palm tocotrienol-rich fraction improves vascular proatherosclerotic changes in hyperhomocysteinemic rats

Norsidah KZ, Asmadi AY, Azizi A, Faizah O, Kamisah Y

Evid Based Complement Alternat Med, 2013;2013:976967.
PMID: 23573162 DOI: 10.1155/2013/976967

This study investigated the effects of palm tocotrienol-rich fraction (TRF) on aortic proatherosclerotic changes in rats fed with a high methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control (fed with a basal diet). Another five groups were fed with 1% methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60, and 150 mg/kg diets) was added into the diet of the last four rat groups, respectively. The high methionine diet raised the plasma total homocysteine and aortic lipid peroxidation, which were reduced by the palm TRF and folate supplementations. Plasma nitric oxide was reduced in the high methionine group compared to the control (3.72 ± 0.57 versus 6.65 ± 0.53 μ mol/L, P < 0.05), which reduction was reversed by the palm TRF (60 and 150 mg/kg) and folate supplementations. The increased aortic vascular cell adhesion molecule-1 expression in the methionine group (2.58 ± 0.29) was significantly reduced by the folate (1.38 ± 0.18) and palm TRF at 150 mg/kg (1.19 ± 0.23). Palm TRF was comparable to folate in reducing high methionine diet-induced plasma hyperhomocysteinemia, aortic oxidative stress, and inflammatory changes in rats.
Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver

Kamisah Y, Norsidah KZ, Azizi A, Faizah O, Nonan MR, Asmadi AY

J Physiol Biochem, 2015 Dec;71(4):659-67.
PMID: 26403767 DOI: 10.1007/s13105-015-0431-y

Oxidative stress plays an important role in cardiovascular diseases. The study investigated the effects of dietary palm tocotrienol-rich fraction on homocysteine metabolism in rats fed a high-methionine diet. Forty-two male Wistar rats were randomly assigned to six groups. Five groups were fed with high-methionine diet (1%) for 10 weeks. Groups 2 to 5 were also given dietary folate (8 mg/kg) and three doses of palm tocotrienol-rich fraction (30, 60 and 150 mg/kg) from week 6 to week 10. The last group was only given basal rat chow. High-methionine diet increased plasma homocysteine after 10 weeks, which was prevented by the supplementations of folate and high-dose palm tocotrienol-rich fraction. Hepatic S-adenosyl methionine (SAM) content was unaffected in all groups but S-adenosyl homocysteine (SAH) content was reduced in the folate group. Folate supplementation increased the SAM/SAH ratio, while in the palm tocotrienol-rich fraction groups, the ratio was lower compared with the folate. Augmented activity of hepatic cystathionine β-synthase and lipid peroxidation content by high-methionine diet was inhibited by palm tocotrienol-rich fraction supplementations (moderate and high doses), but not by folate. The supplemented groups had lower hepatic lipid peroxidation than the high-methionine diet. In conclusion, palm tocotrienol-rich fraction reduced high-methionine-induced hyperhomocysteinaemia possibly by reducing hepatic oxidative stress in high-methionine-fed rats. It may also exert a direct inhibitory effect on hepatic cystathionine β-synthase.
DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients

Nour El Huda AR, Norsidah KZ, Nabil Fikri MR, Hanisah MN, Kartini A, Norlelawati AT

Psychiatry Clin Neurosci, 2018 Apr;72(4):266-279.
PMID: 29160620 DOI: 10.1111/pcn.12622

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.
METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.
RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P
Relationship of selective complement markers with schizophrenia

Mohd Asyraf AJ, Nour El Huda AR, Hanisah MN, Norsidah KZ, Norlelawati AT

J Neuroimmunol, 2022 02 15;363:577793.
PMID: 34990981 DOI: 10.1016/j.jneuroim.2021.577793

Immune system dysregulation may be involved in schizophrenia, but biomarker studies have thus far reported inconsistent findings. The relationship of plasma levels of complement markers C3 and C4, with schizophrenia, sociodemographic and clinico-psychological factors were here studied in 183 patients and 212 controls. C3 and C4 levels were significantly higher in the patients and in subjects with elevated C-reactive protein (CRP), and positively correlated with body mass index (BMI) (p