Publications by authors named "Wiratchanee Mahavorasirikul"

7 Publications

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studies on gastrointestinal monogastric and avian models to evaluate the binding efficacy of mycotoxin adsorbents by liquid chromatography-tandem mass spectrometry.

J Adv Vet Anim Res 2019 Mar 25;6(1):125-132. Epub 2019 Feb 25.

Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.

Objective: The objective of this study is evaluating the efficacies of 11 mycotoxin adsorbent products, marketed in South East Asia. Three prominently occurring mycotoxins; aflatoxin B1 (AFB1), deoxynivalenol (DON), and zearalenone (ZEN) were simultaneously spiked into the samples.

Materials And Methods: Samples were simultaneously tested in vitro in phosphate buffer and simulated at different pH conditions in the gastrointestinal tracts of the porcine and avian model, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: All mycotoxin adsorbent products had high efficacy at over 90% for AFB1 adsorption in both GI porcine and avian models. AFB1 could be adsorbed more in acidic condition than the basic condition. ZEN adsorption was determined to be more stable at pH 3 than pH 6.5 or 8.4, in which pH condition might influence on ZEN desorption rate. DON was poorly adsorbed by all tested agents.

Conclusions: The finding showed that the adsorption rate varied depending on the type of adsorbent. Our results might provide useful information regarding the efficacy of mycotoxin adsorbents commercially marketed in the region.
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March 2019

Inhibitory Activities of Thai Medicinal Plants with Promising Activities Against Malaria and Cholangiocarcinoma on Human Cytochrome P450.

Phytother Res 2015 Dec 22;29(12):1926-33. Epub 2015 Oct 22.

Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.

Malaria and cholangiocarcinoma remain important public health problems in tropical countries including Southeast Asian nations. Newly developed chemotherapeutic and plant-derived drugs are urgently required for the control of both diseases. The aim of the present study was to investigate the propensity to inhibit cytochrome P450-mediated hepatic metabolism (CYP1A2, CYP2C19, CYP2D6 and CYP3A4) of the crude ethanolic extract of eight Thai medicinal plants with promising activities against malaria and cholangiocarcinoma, using human liver microsomes in vitro. Piper chaba Linn. (PC) and Atractylodes lancea (thung.) DC. (AL) exhibited the most potent inhibitory activities on CYP1A2-mediated phenacetin O-deethylation with mean IC50 of 0.04 and 0.36 µg/mL, respectively. Plumbago indica Linn. (PI) and Dioscorea membranacea Pierre. (DM) potently inhibited CYP2C19-mediated omeprazole 5-hydroxylation (mean IC50 4.71 and 6.92 µg/mL, respectively). DM, Dracaena loureiri Gagnep. (DL) and PI showed the highest inhibitory activities on dextromethorphan O-demethylation (mean IC50 2.93-9.57 µg/mL). PC, DM, DL and PI exhibited the most potent inhibitory activities on CYP3A4-mediated nifedipine oxidation (mean IC50 1.54-6.43 µg/mL). Clinical relevance of the inhibitory potential of DM, PC and PI is of concern for the further development of these plants for the treatment of malaria and/or cholangiocarcinoma.
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December 2015

Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines.

Asian Pac J Cancer Prev 2011 ;12(1):55-9

Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Bangkok, Thailand.

Cytotoxic activity of artemisinin and derivatives in the presence and absence of holo-transferrin and expression of genes involved in resistance of cancer cells were investigated in human cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines in vitro. After incubation with the test drugs and 5-fluorouracil (5-FU) cytotoxicity was asessed by MTT assay. RNA was extracted after 24 hour exposure to holo-transferrin for invesstigation of the expression of transferrin receptor 1 (TDR1), multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), multidrug resistance protein 2 (MRP2), and multidrug resistance protein 3 (MRP3). The median IC₅₀ of artemisinin, artesunate, artemeter, dihydroartemisinin and 5-FU were as follows: CL-6: 339, 131, 354, 75, and 377 microM, respectively; Hep-G2: 268, 50, 233, 29, and 1,380 microM. Exposure to holo-transferrin had no influence on sensitivity of either cell line to artemisinin derivatives, but resulted in a 3-fold increase in the expression of TR1 and MDR1, and a 2-fold increase in the expression of MRP1 and MRP2 in CL-6 cells. With Hep-G2, a 3-fold increase in the expression of MDR1 and MRP3 and a 2-fold increase in expression of MRP2 were observed. Dihydroartemisinin exhibited the most potent cytotoxic activity against both cell lines and holo-transferrin caused different patterns of expression of resistance-associated genes.
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May 2012

Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro.

BMC Complement Altern Med 2010 Sep 28;10:55. Epub 2010 Sep 28.

Graduate Program in Biomedical Sciences, Thammasat University (Rangsit Campus), Pathumtani 12121, Thailand.

Background: Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.

Methods: Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated.

Results: The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50=9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50=757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50=24.09 μg/ml, SI = 8.6).

Conclusions: The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.
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September 2010

The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population.

Environ Toxicol Pharmacol 2009 Nov 14;28(3):420-4. Epub 2009 Jul 14.

Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Thailand.

We investigated the influence of genetic, cadmium exposure and smoking status, on cytochrome P450-mediated nicotine metabolism (CYP2A6) in 182 Thai subjects after receiving 2mg of nicotine gum chewing for 30min. The urinary excretion of cotinine was normally distributed over a 2h period (logarithmically transformed). Individuals with urinary cotinine levels in the ranges of 0.01-0.21, and 0.52-94.99μg/2h were categorized as poor metabolizes (PMs: 6.5%), and extensive metabolizers (EMs: 93.5%), respectively. The majority of EMs (45%) carried homozygous wild-type genotypes (CYP2A6*1A/*1A, CYP2A6*1A/*1B and CYP2A6*1B/*1B), whereas only 1% of PMs carried these genotypes. Markedly higher frequencies of EMs were also observed in all heterozygous defective genotypes including the null genotype (*4C/*4C; 1 subject). A weak but significant positive correlation was observed between total amounts of urinary cadmium excretion and total cotinine excretion over 2h. Our study shows generally good agreement between CYP2A6 genotypes and phenotypes. Smokers accumulated about 3-4-fold higher mean total amounts of 2-h urinary cadmium excretion (127.5±218.2ng/2h) than that of non-smokers (40.5±78.4ng/2h). Among the smokers (n=16), homologous wild-type genotype *1/*1 was significantly the predominant genotype (6/16) compared with other defective allele including *4C/*4C. In addition, 2h urinary excretion of cotinine in smokers of all genotypes was significantly higher than non-smokers. The proportion of smokers who smoked more than 5 cigarettes/day was significantly higher in EMs in all CYP2A6 genotypes (n=14) than in PMs (n=0).
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November 2009

The influence of iron stores on cadmium body burden in a Thai population.

Environ Geochem Health 2010 Jun 6;32(3):237-42. Epub 2009 Oct 6.

Thammasat University, Pathumthani, Thailand.

Cadmium is a toxin of increasing public health concern due to its presence in most human foodstuffs and in cigarette smoke. Exposure to cadmium leads to tissue bioaccumulation and, in particular, has nephrotoxic effects. The aim of the present study was to investigate the association between cadmium body burden and iron stores in a Thai population. A total of 182 healthy adult Thai subjects of both genders (89 males, 93 females) aged between 18 and 57 years and weighing 40-95 kg were included in this study. The total amounts of cadmium excreted in urine over 2 h (microg/g creatinine) were used as an index of long-term cadmium exposure. Quantitation of cadmium was performed using electrothermal (graphite furnace) atomic absorption spectrometry. The urinary cadmium excreted displayed a normal frequency distribution. The average urinary cadmium level did not exceed the WHO maximum tolerable internal dose for the non-exposed population (2 microg/g creatinine). Body iron stores reflected by serum ferritin levels did not show any correlation with cadmium burden in both males and females, although a relatively stronger influence of body iron store status on cadmium burden was shown in females. When the levels of serum ferritin were stratified into five levels (<20, 20-100, 101-200, 201-300, and >300 microg/l), a significant difference in total cadmium body burden was observed between females and males only in the group with a low level of serum ferritin of <20 microg/l. The cadmium body burden in females was about twice that in males in this group.
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June 2010

CYP2A6 genotypes and coumarin-oxidation phenotypes in a Thai population and their relationship to tobacco smoking.

Eur J Clin Pharmacol 2009 Apr 13;65(4):377-84. Epub 2008 Dec 13.

Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand.

Objective: To investigate the association between polymorphisms in the human CYP2A6 gene, CYP2A6 enzyme activity and the influence of cigarette smoking in a Thai population.

Methods: Coumarin (5 mg capsule) was administered to 194 healthy Thai subjects. Genetic variation of the CYP2A6 gene was identified using PCR methods. The excreted dose of 7-hydroxycoumarin (as a percentage of the urine concentration) 2 h after administration was calculated as an index of coumarin metabolism.

Results: The frequencies of CYP2A6 alleles *1A, *1B, *4C, *7, *8, *9 and *10 were 34.0, 35.3, 9.3, 6.4, 0.5, 12.1 and 2.4%, respectively. Of the 194 subjects tested, the number (percentages) of Thai participants classified as ultra-rapid, extensive, intermediate and poor metabolizers were 8 (4.1%), 159 (82.0%) 22 (11.3%) and five (2.6%), respectively.

Conclusion: A relationship between the interindividual differences in coumarin metabolism and genetic polymorphisms of the CYP2A6 gene was observed.
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April 2009