Cytotoxic and inflammatory responses of TiO2 nanoparticles on human peripheral blood mononuclear cells.

Titanium dioxide nanoparticles (TiO2 -NPs) have been widely used in many applications. Owing to their nanoscale size, interactions between cells and NPs have been expansively investigated. With the health concerns raised regarding the adverse effects of these interactions, closer examination of whether TiO2 -NPs can induce toxicity towards human cells is greatly needed.

Environmental lead exposure, catalase gene, and markers of antioxidant and oxidative stress relation to hypertension: an analysis based on the EGAT study.

Lead has been linked to the development of hypertension via oxidative stress. Catalase plays an important role in the disposal of hydrogen peroxide in erythrocyte and its activity was determined by CAT gene. The aims of this study were to investigate (1) the association between blood levels of antioxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase, oxidative stress-marker (malondialdehyde), and blood lead level and (2) the influence of genetic polymorphism of CAT gene (rs769217) on change in blood pressure in general population of EGAT study project.

Effects of amino acid substitutions at positions 33 and 37 on UDP-glucuronosyltransferase 1A9 (UGT1A9) activity and substrate selectivity.

UGT1A9 contributes to the glucuronidation of numerous drugs and xenobiotics. There is evidence to suggest that the Met33Thr substitution, as occurs in the polymorphic variant UGT1A9*3, variably affects xenobiotic glucuronidation. The equivalent position in UGT1A4 is also known to influence enzyme activity, whilst an N-terminal domain histidine (His37 in UGT1A9) is believed to function as the catalytic base in most UGT enzymes.

The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentration in Thai bus drivers.

Polycyclic aromatic hydrocarbons (PAHs) are associated with an increased cancer risk. CYP1A1 and GSTs enzymes are important in metabolism of PAHs. Genetic polymorphisms of these enzymes are responsible for enzyme activity and concentration variation.

Three novel single nucleotide polymorphisms of UGT1A9 in a Thai population.

The human UDP-glucuronosyltransferase, UGT1A9, catalyzes glucuronidation of various endobiotics and xenobiotics. In this study, we sequenced the promoter and exon 1 regions of the UGT1A9 gene in 93 Thai individuals and identified 7 genetic polymorphisms. The allele frequencies of all 3 novel single nucleotide polymorphisms (SNPs): 454A>G and 455A>C (N152A) and 760C>T (R254X) were 0.

Cholinesterase activity, pesticide exposure and health impact in a population exposed to organophosphates.

Objective: Biological monitoring is an essential component for assessing the exposure of individuals to organophosphate pesticides. The aim of this study was to determine cholinesterase activity, pesticide exposure and health effects in the exposed population.

Methods: A total of 90 individuals occupationally exposed to OPs and 30 controls were recruited in this study.

Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates.

Objectives: UGT1A1 coding region mutations, including UGT1A1*6 (G71R), UGT1A1*7 (Y486D), UGT1A1*27 (P229Q) and UGT1A1*62 (F83L), have been linked to Gilbert syndrome in Asian populations, whereas homozygosity for UGT1A1*7 is associated with the Crigler-Najjar syndrome type II. This work compared the effects of (a) the individual UGT1A1 mutations on the glucuronidation kinetics bilirubin, beta-estradiol, 4-methylumbelliferone (4MU) and 1-naphthol (1NP), and (b) the Y486 mutation, which occurs in the conserved carboxyl terminal domain of UGT1A enzymes, on 4MU, 1NP and naproxen glucuronidation by UGT1A3, UGT1A6 and UGT1A10.

Methods: Mutant UGT1A cDNAs were generated by site-directed mutagenesis and the encoded proteins were expressed in HEK293 cells.

Paraoxonase (PON1) polymorphism and activity as the determinants of sensitivity to organophosphates in human subjects.

Paraoxonase (PON1) plays an important role in mechanism of organophosphorus compound (OP) toxicity, as seen both in vitro and in vivo studies. Polymorphisms of PON1 gene at coding and promoter regions have also been to affect on the hydrolytic activity and PON1 level. The objectives of this study were to determine PON1 polymorphism and activity in an OP-exposed population and the effects on inhibition of cholinesterase activity.

No direct hepatotoxic potential following a multiple-low dose paraquat exposure in rat as related to its bioaccumulation.

Paraquat (PQ) is a well-known toxic bipyridyl herbicide commonly used in agricultural countries. Pulmonary toxicity is the main cause of death but damage to other organs has also been reported. PQ is also classified as a "direct hepatotoxicant" following an acute high dose exposure.

In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais.

The association between the distribution characteristics of CYP2A6 catalytic activities toward nicotine and coumarin, and the frequency distribution of CYP2A6 variant alleles reported was estimated in 120 healthy Thais. The distributions of the subjects as classified by the amounts of 7-hydroxycoumarin (7-OHC) excreted in the urine and by cotinine/nicotine ratio in the plasma were clearly bimodal. However, the numbers of apparently poor metabolizers for coumarin and nicotine were different.

Differential contribution of active site residues in substrate recognition sites 1 and 5 to cytochrome P450 2C8 substrate selectivity and regioselectivity.

Selected active site residues in substrate recognition sites (SRS) 1 and 5 of cytochrome P450 2C8 (CYP2C8) were mutated to the corresponding amino acids present in CYP2C9 to investigate the contribution of these positions to the unique substrate selectivity and regioselectivity of CYP2C8. The effects of mutations, singly and in combination, were assessed from changes in the kinetics of paclitaxel 6alpha-hydroxylation, a CYP2C8-specific pathway, and the tolylmethyl and ring hydroxylations of torsemide, a mixed CYP2C9/CYP2C8 substrate. Within SRS1, the single mutation S114F abolished paclitaxel 6alpha-hydroxylation, while the I113V substitution resulted in modest parallel reductions in K(m) and V(max).

Attenuation of paraquat-induced motor behavior and neurochemical disturbances by L-valine in vivo.

Alterations of motor behavioral patterns and monoamine contents in the discrete rat brain areas after acute paraquat exposure (3, 5, 10, 20 mg/kg, s.c.) have been studied.

Anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene from Zingiber cassumunar Roxb.

This study aimed to investigate the anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD), isolated from Zingiber cassumunar Roxb., using in vivo and in vitro models. The results show that DMPBD dose-dependently inhibited the rat ear edema induced by ethyl phenylpropiolate (EPP), arachidonic acid (AA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) and it was more potent than any other standard drugs being used.