Treatment Heterogeneity of Water, Sanitation, Hygiene, and Nutrition Interventions on Child Growth by Environmental Enteric Dysfunction and Pathogen Status for Young Children in Bangladesh.

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth. Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates. Results: We analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) and Campylobacter infection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase or Campylobacter infection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention. Conclusions: These findings indicate that EED biomarker and pathogen status, particularly Campylobacter and myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.

Determinants of livelihood diversification in rural rain-fed region of Pakistan: evidence from fractional multinomial logit (FMLOGIT) estimation.

Sustainable livelihoods in less developed countries are threatened by human, natural, physical, social and financial factors. Pakistan is also facing severe negative impacts of these factors in the form of climate shocks, market imperfections and insufficient formal credit availability on rural livelihoods. This study explores rural Pakistani's adaptation to these threats by diversifying income sources and explores the determining factors for adopting specific livelihood diversification strategies. The study is based on a quantitative survey of 295 households in three districts of rain-fed rural regions of Pakistan's Punjab with differing annual rainfall. Results showed that households mitigated against threats to their livelihood by having a diversity of income sources (Simpson Diversity Index = 0.61). Moreover, fractional multinomial regression modelling revealed that greater education was associated with a more diversified livelihood strategy, where income was predominantly derived from off-farm and non-farm livelihood activities. On the other hand, households with older members, more livestock and larger farm size focused their livelihoods on their own farms, or primarily diversified into an off-farm strategy by working on other farms. These findings underscore the importance of improved access to education and infrastructure for livelihood diversification. A policy that focuses on reducing low literacy rates in rural Pakistan may also provide new avenues of livelihood diversifications with enhancement of rural literacy rate to mitigate the risks associated with livelihood strategies of smallholders.

Electrochemical Detection of Dihydroxybenzene Isomers at a Pencil Graphite Based Electrode.

In this work, an HB pencil electrode (HBPE) was electrochemically modified by amino acids (AAs) glycine (GLY) and aspartic acid (ASA) and designated as GLY-HB and ASA-HB electrodes. They were used in the detection of dihydroxybenzene isomers (DHBIs) such as hydroquinone (HQ), catechol (CC), and resorcinol (RS), by cyclic voltammetry (CV), and by differential pulse voltammetry. HBPE was characterized by scanning electron microscopy and energy-dispersive X-ray spectroscopy. These three electrodes showed a linear relationship of current with concentration of DHBIs, and the electrochemical processes were diffusion controlled in all cases. In simultaneous detection, the limit of detection, based on signal-to-noise ratio (S/N = 3), for HQ, CC, and RS was 12.473, 16.132, and 25.25 µM, respectively, at bare HBPE; 5.498, 7.119, and 14.794 µM, respectively, at GLY-HB; and 22.459, 25.478, and 38.303 µM, respectively, at ASA-HB. The sensitivity for HQ, CC, and RS was 470.481, 363.781, and 232.416 µA/mM/cm2, respectively, at bare HBPE; 364.785, 282.712, and 135.560 µA/mM/cm2, respectively, at GLY-HB; and 374.483, 330.108, and 219.574, respectively, at ASA-HB. The interference studies clarified the suitability and reliability of the electrodes for the detection of HQ, CC, and RS in an environmental system. Real sample analysis was done using tap water, and the proposed electrodes expressed recovery with high reproducibility. Meanwhile, these three electrodes have excellent sensitivity and selectivity, which can be used as a promising technique for the detection of DHBIs simultaneously.

Bioaccessibility and speciation of arsenic in children's diets and health risk assessment of an endemic area in Bangladesh.

This study determines the bioaccessibility of toxic and carcinogenic arsenic (As) in composite food samples and evaluates potential exposure from food intake in Bangladesh children. Total As (tAs), inorganic As (iAs) and bioaccessible As (BAs) in food composite samples consumed by children were compared between an exposed and a control group (based on As in drinking water). Total As concentrations in composite food samples of children exposed to mean As level of 331 µg/l in drinking and cooking water ranged from 586 to 1975 µg/kg, dry weight over 76-90 µg/kg in the unexposed group. Average iAs in food composites was 73.9% (range: 49.3-90.8%). The fraction of BAs using gastric and gastrointestinal phases was 91 ± 13% and 98 ± 11%, respectively. Daily intake of iAs in the exposed group ranged from 0.41 to 6.38 µg per kg body weight (BW), which was much higher than the unexposed group (0.08-0.15 µg per kg BW). High iAs content and BAs in composite food samples indicated the elevated risk to exposed children. Further research should include both adults and children using larger sample size to determine overall As exposure from food intake in Bangladesh, attention must be given to lowering of As in food.

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh.

BACKGROUND: We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. METHODS: Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1ß) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. RESULTS: We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53). CONCLUSIONS: Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health. CLINICAL TRIALS REGISTRATION: NCT01590095.

Structures of aniline(pyrrole)+, aniline(ethanol)+, and aniline-(benzene).

Molecular structures of aniline(pyrrole)+, aniline(ethanol)+, and aniline(benzene)+ produced via resonance two-photon ionization at 266 nm were analyzed by infrared predissociation spectroscopy coupled with tandem mass spectrometry. Structural optimization and frequency calculation using density functional theory were carried out to suggest the most probable isomers which are in good agreement with the observed infrared absorption spectra. Intermolecular bonds in the cluster ions were formed such that the electronegative oxygen atom of the solvent molecule or the pi electron of the aromatic ring forms a hydrogen bonding to NH of aniline.

Assessment of Nutritional Status of Infants Living in Arsenic-Contaminated Areas in Bangladesh and Its Association with Arsenic Exposure.

Data is scarce on early life exposure to arsenic and its association with malnutrition during infancy. This study followed the nutritional status of a cohort of 120 infants from birth to 9 months of age in an arsenic contaminated area in Bangladesh. Anthropometric data was collected at 3, 6 and 9 months of the infant's age for nutritional assessment whereas arsenic exposure level was assessed via tube well drinking water arsenic concentration at the initiation of the study. Weight and height measurements were converted to Z-scores of weight for age (WAZ-underweight), height for age (HAZ-stunting), weight for height (WHZ-wasting) for children by comparing with WHO growth standard. Arsenic exposure levels were categorized as <50 µg/L and ≥50 µg/L. Stunting rates (<-2 SD) were 10% at 3 months and 44% at both 6 and 9 months. Wasting rates (<-2 SD) were 23.3% at 3 months and underweight rates (<-2 SD) were 25% and 10% at 3 and 6 months of age, respectively. There was a significant association of stunting with household drinking water arsenic exposure ≥50 µg/L at age of 9 months (p = 0.009). Except for stunting at 9 months of age, we did not find any significant changes in other nutritional indices over time or with levels of household arsenic exposure in this study. Our study suggests no association between household arsenic exposure and under-nutrition during infancy; with limiting factors being small sample size and short follow-up. Difference in stunting at 9 months by arsenic exposure at ≥50 µg/L might be a statistical incongruity. Further longitudinal studies are warranted to establish any association.

Selenium-mediated arsenic excretion in mammals: a synchrotron-based study of whole-body distribution and tissue-specific chemistry.

Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers", we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic-selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.

Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile.

Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe](-). Previous work has definitively demonstrated the presence of [(GS)2AsSe](-) in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe](-). Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe](-), with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.

Intrinsic Folding Proclivities in Cyclic ß-Peptide Building Blocks: Configuration and Heteroatom Effects Analyzed by Conformer-Selective Spectroscopy and Quantum Chemistry.

This work describes the use of conformer-selective laser spectroscopy following supersonic expansion to probe the local folding proclivities of four-membered ring cyclic ß-amino acid building blocks. Emphasis is placed on stereochemical effects as well as on the structural changes induced by the replacement of a carbon atom of the cycle by a nitrogen atom. The amide A IR spectra are obtained and interpreted with the help of quantum chemistry structure calculations. Results provide evidence that the building block with a trans-substituted cyclobutane ring has a predilection to form strong C8 hydrogen bonds. Nitrogen-atom substitution in the ring induces the formation of the hydrazino turn, with a related but distinct hydrogen-bonding network: the structure is best viewed as a bifurcated C8/C5 bond with the N heteroatom lone electron pair playing a significant acceptor role, which supports recent observations on the hydrazino turn structure in solution. Surprisingly, this study shows that the cis-substituted cyclobutane ring derivative also gives rise predominantly to a C8 hydrogen bond, although weaker than in the two former cases, a feature that is not often encountered for this building block.

Groundwater arsenic contamination in Bangladesh-21 Years of research.

Department of Public Health Engineering (DPHE), Bangladesh first identified their groundwater arsenic contamination in 1993. But before the international arsenic conference in Dhaka in February 1998, the problem was not widely accepted. Even in the international arsenic conference in West-Bengal, India in February, 1995, representatives of international agencies in Bangladesh and Bangladesh government attended the conference but they denied the groundwater arsenic contamination in Bangladesh. School of Environmental Studies (SOES), Jadavpur University, Kolkata, India first identified arsenic patient in Bangladesh in 1992 and informed WHO, UNICEF of Bangladesh and Govt. of Bangladesh from April 1994 to August 1995. British Geological Survey (BGS) dug hand tube-wells in Bangladesh in 1980s and early 1990s but they did not test the water for arsenic. Again BGS came back to Bangladesh in 1992 to assess the quality of the water of the tube-wells they installed but they still did not test for arsenic when groundwater arsenic contamination and its health effects in West Bengal in Bengal delta was already published in WHO Bulletin in 1988. From December 1996, SOES in collaboration with Dhaka Community Hospital (DCH), Bangladesh started analyzing hand tube-wells for arsenic from all 64 districts in four geomorphologic regions of Bangladesh. So far over 54,000 tube-well water samples had been analyzed by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). From SOES water analysis data at present we could assess status of arsenic groundwater contamination in four geo-morphological regions of Bangladesh and location of possible arsenic safe groundwater. SOES and DCH also made some preliminary work with their medical team to identify patients suffering from arsenic related diseases. SOES further analyzed few thousands biological samples (hair, nail, urine and skin scales) and foodstuffs for arsenic to know arsenic body burden and people sub-clinically affected. SOES and DCH made a few follow-up studies in some districts to know their overall situations after 9 to 18 years of their first exposure. The overall conclusion from these follow-up studies is (a) villagers are now more aware about the danger of drinking arsenic contaminated water (b) villagers are currently drinking less arsenic contaminated water (c) many villagers in affected village died of cancer (d) arsenic contaminated water is in use for agricultural irrigation and arsenic exposure from food chain could be future danger. Since at present more information is coming about health effects from low arsenic exposure, Bangladesh Government should immediately focus on their huge surface water management and reduce their permissible limit of arsenic in drinking water.

Intra-residue interactions in proteins: interplay between serine or cysteine side chains and backbone conformations, revealed by laser spectroscopy of isolated model peptides.

Intra-residue interactions play an important role in proteins by influencing local folding of the backbone. Taking advantage of the capability of gas phase experiments to provide relevant information on the intrinsic H-bonding pattern of isolated peptide chains, the intra-residue interactions of serine and cysteine residues, i.e., OH/SH···OC(i) C6 and NH(i···)O/S C5 interactions in Ser/Cys residues, are probed by laser spectroscopy of isolated peptides. The strength of these local side chain-main chain interactions, elegantly documented from their IR spectral features for well-defined conformations of the main chain, demonstrates that a subtle competition exists between the two types of intra-residue bond: the C6 H-bond is the major interaction with Ser, in contrast to Cys where C5 interaction takes over. The restricted number of conformers observed in the gas phase experiment with Ser compared to Cys (where both extended and folded forms are observed) also suggests a significant mediation role of these intra-residue interactions on the competition between the several main chain folding patterns.

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

BACKGROUND: Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine. METHODS: Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation. RESULTS: Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 µg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 µg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant's urine increased non-significantly by 0.13 µg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant's urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine. CONCLUSIONS: We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization's maximum permissible limit (WHO Permissible Limit 15 µg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

Direct spectroscopic evidence of hyperconjugation unveils the conformational landscape of hydrazides.

The stereochemistry of hydrazides makes them especially interesting as building blocks for molecular design. An exhaustive conformational analysis of three model hydrazides was conducted in a conformer-selective approach by using a combination of high-level quantum chemistry calculations and vibrational spectroscopy in the gas phase and in solution. The NH stretch frequency was found to be highly sensitive to hyperconjugation, thus making it an efficient probe of the conformation of the neighboring nitrogen atom. This property greatly assisted the identification of the isomers observed experimentally in the conformer pool. A rationalization of the hydrazide conformational landscape is proposed, therefore paving the way for a better characterization of secondary structures in larger systems.

Design of high speed and low offset dynamic latch comparator in 0.18 µm CMOS process.

The cross-coupled circuit mechanism based dynamic latch comparator is presented in this research. The comparator is designed using differential input stages with regenerative S-R latch to achieve lower offset, lower power, higher speed and higher resolution. In order to decrease circuit complexity, a comparator should maintain power, speed, resolution and offset-voltage properly. Simulations show that this novel dynamic latch comparator designed in 0.18 µm CMOS technology achieves 3.44 mV resolution with 8 bit precision at a frequency of 50 MHz while dissipating 158.5 µW from 1.8 V supply and 88.05 µA average current. Moreover, the proposed design propagates as fast as 4.2 nS with energy efficiency of 0.7 fJ/conversion-step. Additionally, the core circuit layout only occupies 0.008 mm2.

On the near UV photophysics of a phenylalanine residue: conformation-dependent ππ* state deactivation revealed by laser spectroscopy of isolated neutral dipeptides.

The primary step of the near UV photophysics of a phenylalanine residue is investigated in one- and two-color pump-probe R2PI nanosecond experiments carried out on specific conformers of the Ac-Gly-Phe-NH2 molecule and related neutral compounds isolated in a supersonic expansion. Compared to toluene, whose ππ* state photophysics is dominated by intersystem crossing with a lifetime of ∼80 ns at the origin, the first ππ* state of Phe in the peptide environment is systematically found to be shorter-lived. The lifetime at the origin of transition is found to be significantly shortened in the presence of a primary amide (-CONH2) group (20-60 ns, depending on the conformer considered), demonstrating the existence of an additional non-radiative relaxation channel related to this chemical group. The quenching effect induced by the peptide environment is still more remarkable beyond the origin of the ππ* state, since vibronic bands of one of the 4 conformers observed (the 27-ribbon conformation) become barely detectable in the ns R2PI experiment, suggesting a significant conformer-selective lifetime shortening (below 100 ps). These results on dipeptides, which extend previous investigations on shorter Phe-containing molecules (N-Ac-Phe-NH2 and N-Ac-Phe-NH-Me), confirm the existence of conformer-dependent non-radiative deactivation processes, whose characteristic timescales range from tens of ns down to hundreds of ps or below. This dynamics is assigned to two distinct mechanisms: a first one, consistent with an excitation energy transfer from the optically active ππ* state to low-lying amide nπ* excited states accessed through conical intersections, especially in the presence of a C-terminal primary amide group (-CONH2); a second one, responsible for the short lifetimes in 2(7) ribbon structures, would be more specifically triggered by phenyl ring vibrational excitations. Implications in terms of spectroscopic probing of Phe in a peptide environment, especially in the presence of a quenching amide group, are discussed.

Speciation of arsenic metabolite intermediates in human urine by ion-exchange chromatography and flow injection hydride generation atomic absorption spectrometry.

Biomethylation is considered as the principal metabolic and detoxification pathway for inorganic arsenic in human. The end products of methylation are less toxic and more readily excreted through urine. Therefore, speciation of metabolites in urine is essential to a better understanding of arsenic metabolism, health effects and detoxification ability of individuals exposed to arsenic through drinking water, food and environmental materials. Speciation of inorganic and methylated arsenic in urine is an analytical challenge and often requires expensive instrumentation. We have applied a relatively inexpensive technique for the separation and analysis of various arsenic species, such as, arsenite, arsenate, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in human urine. The technique is based on ion exchange chromatographic separation followed by flow injection hydride generation atomic absorption spectroscopy (FI-HG-AAS). The detection limit varies from 1.0 to 2.0 microg/L for various species. The technique has been successfully applied to speciation of arsenic metabolite intermediates in urine samples collected from patients in Hajiganj, a serious arsenic affected area in Bangladesh. Arsenite (AsIII) was found to be the major component in the urine from these patients. Our findings from patients in Hajiganj, Bangladesh are presented in this paper. The technique permits us to carry out arsenic speciation in urine, essential for toxicological studies and possible nutritional intervention in combating arsenic poisoning in Bangladesh.

Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: preliminary results.

To assess the oxidative injuries caused by arsenic toxicity in rabbits and evaluate the detoxifying effects of exogenous antioxidants, we administered arsenic trioxide (3-5 mg/kg/day) in rabbits through a feeding tube for seven days. These rabbits were then treated with a recipe of vitamins, zinc, selenium (VZS) or a plant polyphenol or a placebo for the next seven days. Blood samples were collected from ear vein for spectrophotometric assay of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and nitrite/nitrate (NOx; index of nitric oxide formation) before arsenic administration, seven days after arsenic administration, and seven days after antioxidant treatment. The total arsenic concentrations in hair and spot urine samples of rabbits before arsenic administration were 0.6 +/- 0.21 microg/g and 34.0 +/- 5.9 microg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 +/- 0.40 microg/g (p<0.001) and 7372 +/- 1392.0 microg/L (p<0.001), respectively. Arsenic administration to rabbits significantly reduced GSH concentration (post-arsenic, 17.5 +/- 0.81 mg/dL vs. pre-arsenic, 32.0 +/- 0.76 mg/dL, p<0.001), increased TBARS concentration (post-arsenic, 8 +/- 1.1 microM vs. pre-arsenic, 5 +/- 0.7 microM, p<0.05), and NOx concentration (post-arsenic, 465 +/- 38.5 microM vs. pre-arsenic, 320 +/- 24.7 microM, p<0.001) as compared to the pre-arsenic levels. There was a negative correlation between TBARS and GSH concentrations (r=-0.464, p<0.01) and between NOx and GSH concentrations (r=-0.381, p<0.05) of intoxicated rabbits. The recovery of the depleted GSH was significantly greater in the polyphenols (77.0 +/- 12.0%) or VZS (67.0 +/- 17.0%) treatment groups compared with the placebo group (36.0 +/- 7.0%). The decrease in NOx level of arsenic-treated rabbits was significantly greater in polyphenols treatment group than the placebo group (60.0 +/- 9.0% vs. 17.0 +/- 6.0%, p<0.001). These results indicate that arsenic induces toxicity in rabbits associated with an increase in lipid peroxidation. Arsenic toxicity increases nitric oxide production in the body. Exogenous antioxidants such as polyphenols and recipe of vitamins, zinc, and selenium are useful for arsenic detoxification.