Inhalation exposure of rats to metal aerosol. II. Study of mutagenic effect on alveolar macrophages.

The effects of inhalation exposure to metal aerosol derived from nickel refinery waste were studied on the frequency of chromosome aberrations in alveolar macrophages in Wistar rats. A 4-month exposure period resulted in significant (P less than 0.01) increases in chromosome aberrations. Relatively high variability without statistical significance was observed after a 4-week exposure period. Increase in damaged alveolar macrophages with the length of exposure seems to point to the role of pulmonary metal deposits. Comparison of the results with those found after 6 months of exposure in bone marrow cells confirmed that metal particles in nickel refinery waste are genotoxic. Thus, this study indicates that alveolar macrophages are suitable for monitoring the genotoxic potential of hazardous chemicals administered by inhalation.     

Perinatal sidestream cigarette smoke exposure and the developing pulmonary surfactant system in rats.

1. Epidemiological studies have strongly implicated passive smoking with increased incidence of various respiratory diseases in children. Our earlier studies have shown that chronic exposure to tobacco smoke significantly changes the composition and the surface activity of the pulmonary surfactant in adult rats. The aim of the present study was to determine if perinatal exposure to sidestream cigarette smoke influences the composition and function of pulmonary surfactant system in developing rat pups. 2. Pregnant Sprague Dawley rats were exposed to sidestream cigarette smoke in a whole body exposure chamber for a total of 6 h each day and the pups born to these dams were further exposed to sidestream smoke for 2 h/day during postnatal period. Exposure of animals to smoke was ascertained by measuring their plasma cotinine. Surfactant analysis was performed on bronchoalveolar lavage fluids (BALF) collected from pups on postnatal day 1, 3, 7, 14, 21 and 35. The phospholipid (PL) content, percentage disaturated phosphatidylcholine (DSPC) and surfactant proteins (SP-A and SP-B) in BALF surfactant preparations from sham and smoke-exposed pups were compared. 3. Significant differences between the two groups were observed at two exposure points: a reduced level of SP-A on day 1, and, a higher level of SP-A and PLs on day 21, in smoke-exposed pups. Surface activity analysis of the surfactant films by pulsating bubble surfactometer did not show any significant differences between the sham and smoke-exposed groups at any exposure point. 4. The results indicate that perinatal exposure to sidestream smoke is capable of producing biochemical changes in the composition of pulmonary surfactant at different stages of development but these changes do not influence surface tension reducing properties of the surfactant.     

Effects of chronic exposure to ozone on pulmonary lipids in rats

Ozone is the most toxic component of photochemical oxidant air pollution. Exposure to high concentrations of ozone produces a variety of toxic effects in the lung, but it is not known to what extent prolonged exposure to low concentrations of ozone may contribute to the development of chronic lung disease. Phospholipids, important components of cellular membranes and surfactant, are necessary for the maintenance of normal lung structure and function. In order to test the effects of chronic exposure to environmentally relevant concentrations of ozone on phospholipid metabolism in the lung, rats were exposed to clean air or to 0.12, 0.25 or 0.50 ppm ozone for up to 18 months. The content and biosynthesis of phospholipids in both lung tissue and bronchopulmonary lavage fluid (surfactant) were measured. Incorporation of [14C]acetate into lung tissue phospholipids, an estimate of overall biosynthesis, decreased significantly at some time points in the study, while tissue phospholipid content tended to increase with both ozone concentration and with age. No changes were detected in phospholipid content of bronchopulmonary lavage fluid. These findings did not support the hypothesis that prolonged exposure of rats to environmentally relevant concentrations of ozone results in either qualitative or quantitative deficits in the pulmonary surfactant system.     

Effects of nitrous acid exposure on baseline pulmonary resistance and Muc5ac in rats

We examined the baseline pulmonary resistance (RLung), baseline dynamic lung compliance (Cdyn), cytokine inductions, and histological alterations in rats exposed to nitrous acid (HONO) with secondary products of nitrogen dioxide (NO₂) and nitric oxide (NO) to assess its biological effects. We exposed three groups of nine male F344 rats to different doses of HONO for six weeks (24?h/day). The cumulative values of HONO concentration were measured twice. The average concentrations of nitrogen oxide for each group were 5.8 parts per million (ppm) HONO with secondary products of 0.7?ppm NO₂ and 2.3?ppm NO, 4.1?ppm HONO with 0.1?ppm NO₂ and 0.6?ppm NO, and a clean air control. We measured baseline RLung and baseline Cdyn using tracheal cannulation. A tracheal tube was inserted into the trachea by tracheostomy, and lung function measurements (baseline RLung and baseline Cdyn) were conducted in mechanically ventilated rats. We measured mRNA levels of Cxcl-1, TNF-α, and Muc5ac in the right lung using quantitative RT-PCR, and observed histological alterations and the alveolar mean linear intercept (Lm) on the left lung. Our results demonstrated that HONO exposure significantly increased baseline RLung, Lm and Muc5ac expression, but did not affect baseline Cdyn or expression of Cxcl-1 and TNF-α. Further, we identified bronchial smooth muscle hypertrophy, pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, and increased goblet cells in HONO-exposed rats. The present results suggest that HONO (with secondary products) adversely affects respiratory function, but that these pathologies may be unrelated to inflammation.     

Inhalation toxicity of propineb. Part I: Results of subacute inhalation exposure studies in rats

This article addresses results from repeated 1- and 4-wk inhalation exposure studies in Wistar rats with solid aerosol (dust) atmospheres of propineb, a zinc bisdithiocarbamate homopolymer that is used as an agrochemical fungicide. Groups of 10 rats/sex were exposed nose-only to mean concentrations of 3.97, 11.24, and 21.95 mg propineb/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean concentrations of 10.1, 19.9, 38.1, and 78.7 mg/m(3). Both studies demonstrated that with respect to muscular effects female rats were remarkably more susceptible as compared to males. Female rats exposed to 11.24 mg/m(3) and above displayed characteristic signs of toxicity that included weakness and flaccid paralysis of hindlegs and ensuing immobilization that was considered to be the cause of emaciation and ensuing mortality in some rats. There was an apparent reciprocal relationship of concentration and the manifestation of clinical evidence of muscular dysfunction; that is, the onset in female rats exposed to 11.24, 21.95, 38.1, and 78.7 mg/m(3) was on days 15, 8, 4, and 3, respectively. In contrast, none of the male rats elaborated comparable effects up to 38.1 mg/m(3). Neuromuscular measures included leg grip strength and supplemented the clinical findings, whereas the landing foot splay was only minimally affected. Hematology and clinical pathology endpoints, including those addressing thyroidal function, were unobtrusive up to and including 78.7 mg/m(3). Lung weights were significantly increased in groups exposed to 21.95 mg/m(3) and above, especially in male rats. The microscopic examinations made in the 4-wk study demonstrated an increased incidence of intraalveolar material and enlarged, foamy alveolar macrophages at 3.97 mg/m(3) and above. Especially in female rats an atrophy of thigh muscle fibers, including increased nuclei and focal degeneration, occurred at 11.24 mg/m(3) and above. TTCA (2-thiazolidinethione-4-carboxylic acid) in urine, a metabolite and biomarker of exposure to CS(2), which is a putative breakdown product of propineb, was proportionally higher in the female rats exposed to 11.24 mg/m(3) and above. This biomarker appears to accumulate with time. This finding provides indirect evidence that the etiopathologic cause of neuromuscular changes is related to intermediary levels of CS(2). The data of this investigation suggest that the toxicity of inhaled propineb is characterized by two independent effects, namely, responses occurring at the alveolar level and muscular weakness, especially in female rats. With respect to the latter finding, the no-observed-adverse-effect level (NOAEL) of the 4-wk study is 3.97 mg/m(3). Further study is needed to clarify whether the pulmonary response observed at this exposure level is consistent with an adaptive or an early adverse effect.     

Inhalation toxicity of potassium octatitanate fibers (TISMO) in rats following 13 weeks of aerosol exposure

One hundred and forty male and 140 female rats were divided into 1 control and 3 test groups of 35 rats each, per sex, and exposed by whole-body inhalation to test compound at target concentrations of 0, 1 mg/m(3) (1700 fibers/cm(3), 123 WHO fibers/cm(3)), 10 mg/m(3) (5900 fibers/cm(3), 952 WHO fibers/cm(3)), and 100 mg/m(3) (112,700 fibers/cm(3), 7440 WHO fibers/cm(3)) for 6 h/day, 5 days/wk for 13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of recovery, respectively, for histopathological evaluation. The other 15 rats from each group were killed to study lung clearance after 91 days of exposure, and approximately 1.5 and 3 mo of recovery following the end of the 13 wk of exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8 microm, while the mean fiber width was 0.48, 0.48, and 0.45 microm for the 1-, 10-, and 100-mg/m(3) chambers, respectively. In the 1-mg/m(3) (123 WHO fibers/cm(3)) exposure group, inhaled particles were mostly retained in a few fiber-laden alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without any adverse tissue response throughout 13 wk of exposure and following 13 wk of recovery. This exposure concentration was considered to be a no-observable-adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs preserved normal structure. After 13 wk of exposure to 10 mg/m(3) (952 WHO fibers/cm(3)), fiber-laden AMs were mainly retained at the alveoli adjacent to the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the alveolar ducts and adjoining alveoli, with proliferating fibroblasts and hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace amounts of collagenous material were deposited in the thickened alveolar ducts and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization was occasionally found in the alveoli adjacent to the terminal bronchioles. The peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber-laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from alveoli located in the peripheral acini, but they localized in the alveolar ducts region, suggesting there was active lung clearance of fibers by the AMs via airways. Thickened alveolar ducts and adjacent alveoli were decreased in thickness, a reversible change manifested by reduction of proliferating Type II pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced in the thickened alveolar ducts and adjoining alveoli. The lung response following 13 wk of exposure to 100 mg/m(3) (7440 WHO fibers/cm(3)) and after 13 wk of recovery was similar to those findings of the 952 WHO fibers/cm(3) group but more pronounced, demonstrating a clear concentration-related response. Alveolar ducts and adjoining alveolar walls in the central acini were irregularly thickened with more frequent evidence of minimal collagenized fibrosis. The lung burden and clearance of fibers were estimated by measuring the total content of titanium (Ti) in the lungs, but high variability of Ti content in control and exposed groups prevented meaningful lung clearance analysis.     

月桂酸维生素C酯的表面活性和抗氧化性的研究

目的考察月桂酸维生素C酯 (DAC)的表面活性和抗氧化性。方法通过测定DAC的亲水亲油平衡值 (HLB)和临界胶束浓度 (cmc)考察DAC的表面活性 ;以DAC和吐温 - 80为乳化剂 ,邻苯三酚为模型化合物 ,制备O/W型乳剂 ;用终止邻苯三酚自氧化的方法考察DAC在水溶液和乳剂中的抗氧化性。结果HLB为 5 4 ,cmc为 7× 10 -5～ 8× 10 -5mol·L-1,O/W型乳剂稳定性良好 ,在溶液和乳剂中DAC均具有抗氧化能力 ,其抗氧化能力与其用量有关。结论DAC具有表面活性和抗氧化性 ,在乳剂中既能作为乳化剂同时又可作为抗氧剂     

Prenatal exposure to cocaine. I: Effects on gestation, development, and activity in Sprague-Dawley rats.

Sperm-positive Sprague-Dawley rats received one of four treatments for 20 days beginning within 24 hours of conception. One group received subcutaneous injections of 15 mg/kg cocaine twice daily (Cocaine-D); a second group received 15 mg/kg cocaine twice daily for two consecutive days at 5-day intervals (Cocaine-I); a third group received normal saline twice daily (Saline); and a fourth group received 1.5 mg/kg amfonelic acid (AFA), a dopamine reuptake inhibitor, once daily. Cocaine-D, Cocaine-I, and AFA dams were fed ad lib. An attempt was made to pair-feed the Saline dams with the Cocaine-D dams; however, the Saline dams did not eat as much as the Cocaine-D dams which resulted in dams in all groups essentially eating ad lib. The Cocaine-D pups showed a slightly delayed righting behavior and neophobia at 30 days of age, as evidenced by hypoactivity during the first 15 min of a 6-h activity test. The Cocaine-I pups were hypoactive during the 3-h dark phase of the 6-h activity test when tested at 30 days of age. These effects did not occur in the offspring exposed to AFA, a potent dopamine uptake inhibitor and CNS stimulant which indicate that one or more other sites for cocaine action may combine for its effects on the developing fetus.     

Effects of nitrous acid exposure on pulmonary tissues in guinea pigs

Many epidemiological studies on the effects of nitrogen dioxide (NO₂) on respiratory function may have included nitrous acid (HONO) exposures in their measures, because conventional NO₂ assays detect HONO as NO₂. A few epidemiological studies and human HONO inhalation experiments have associated HONO with decrements in lung functions. However, there have been few HONO exposure experiments in animals. This study aims to develop a HONO generation system for the animal exposure experiments, and to assess the association of HONO exposure with histopathologic alterations in the respiratory tract of guinea pigs. We exposed the guinea pigs to 3.6?ppm HONO with secondary products of 0.3?ppm NO₂ and 1.6?ppm nitric oxide (NO) for 4 weeks (24?h/day). We conducted histopathologic analyses and measured specific airway resistance (sRaw) from 7?h 40?min to 8?h 30?min after the end of HONO exposure. We found pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, distortion of the centriacinar regions of alveolar ducts with extension of the bronchial epithelial cells and smooth muscle cells, and expansion of bronchial epithelial cells, in the HONO exposure. These histopathologic results suggest that a high concentration of HONO with some NO₂ and NO may associate with decrements in lung functions and some respiratory symptoms. Although the increased tendency of the sRaw value was observed in the HONO exposure group, no statistically significant difference was found between the sRaw values from the HONO exposure group and the filtered air group (p?=?0.06, student’s t-test).     

Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies

The 4-h LC₅ of acetaldehyde in rats was determined and found to be 13 300 ppm (24.0 g/m³ air). In a 4-week study groups of 10 male and 10 female rats were exposed to 0, 400, 1000, 2200 or 5000 ppm acetaldehyde for 6 h/day, 5 days/week. Treatment-related changes observed at the 5000 ppm level included dyspnoea and excitation during the first 30 min of each exposure, yellow-brown fur, severe growth retardation, more neutrophils and less lymphocytes in the blood, a reduced productioon of urine with a high density, increased lung weights, and severe degenerative, hyperplastic and metaplastic changes of the nasal, laryngeal and tracheal epithelium. Major lesions seen at 1000 and 2200 ppm comprised growth retardation and an increased production of urine in males, slight to moderate degeneration with or without hyper- and metaplasia of the nasal epithelium, and only at 2200 ppm, minimal epithelial changes in the larynx and trachea. The only change observed at the 400 ppm level that could be attributed to acetaldehyde was slight degeneration of the nasal olfactory epithelium seen as loss of microvilli and thinning and disarrangement of the layer of epithelial cells.     

抗坏血酸对人肝癌细胞增殖与再分化的作用

AIM: To examine the effects of ascorbic acid (AA) on hepatoma. METHODS: Choosing an all-trans tretinoin (Tre) as a positive control, cell growth, and cell redifferentiation tests by cell surface charges, biochemical changes, and cell growth in soft agar were measured. RESULTS: After being treated with AA 6 mmol.L-1, the growth curve and mitotic index of human hepatoma cells decreased remarkably, the cellular growth inhibitory rate amounted to 58.9%. The indices related with cell malignancy alleviated, such as cell surface charge obviously decreased, the electrophoresis rate dropped from 1.64 microns.s-1.V-1.cm-1 to 0.93, the average value of alpha-fetoprotein (alpha-FP) content decreased from 302 micrograms.g-1(protein) to 90, and gamma-glytamyl-transpeptidase (gamma-GT) activity from 0.81 U.g-1(protein) to 0.16. The index related with cell differentiation increased, such as the average level of tyrosine-alpha-ketoglutarate transminase activity increased from 10.3 micromol.g-1(protein) to 41.2, and the colonogenic potential decreased 94.4%. CONCLUSION: AA can inhibit human hepatoma cells proliferation, induce redifferentiation, and reverse its malignant phenotypic characteristics.     

Inhalation toxicity study of disk-shaped potassium octatitanate particles (Terracess TF) in rats following 90 days of aerosol exposure

Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50?mg/m³ for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4–5 male rats per group or 5 female rats per group were sacrificed at 15?wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9?μm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50?mg/m³ in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10?mg/m³. At 50?mg/m³, some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50?mg/m³. The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9?mo for the 50-mg/m³ group and 2 to 3?mo for the 10- and 2-mg/m³ groups. The lung responses and lung clearance rate were comparable to those of “nuisance” type dusts at these concentrations. Based on interpretation that aggregated particle-laden AMs in alveoli was considered to be an early histopathological sign of lung overloading, an effect level was considered to be 50?mg/m³ and no-observed-adverse-effect level (NOAEL) was 10?mg/m³. This experiment clearly demonstrated that particle morphology was considered to be an important factor to determine inhaled particle toxicity.     

Inhalation exposure to methylene chloride does not induce systemic immunotoxicity in rats

Methylene chloride (dichloromethane) is used in a variety of industrial applications. To date, there has been no formal assessment of immunotoxicity attributed to methylene chloride. Studies were undertaken to examine whether methylene chloride has any potential to influence the integrity of immune function. For this purpose, Sprague-Dawley rats of both genders were exposed by inhalation to a single high dose (5000 ppm) of methylene chloride for 6 h/d, 5 d/wk for 28 d. This was considered the relevant route of administration, as not only is inhalation a primary route for human exposure to methylene chloride, but, also, the chemical is absorbed rapidly via the lungs. Under these conditions of exposure, methylene chloride failed to influence absolute or relative thymus weights in either gender and produced a significant reduction in relative, but not absolute, spleen weight in female rats only. Immunocompetence was measured as a function of the ability of treated animals to mount immunoglobulin M (IgM) antibody responses to sheep red blood cells (SRBC) as determined by enzyme-linked immunosorbent assay (ELISA). Exposure to methylene chloride did not affect antibody production. Evidence indicates that under these conditions of exposure, methylene chloride did not compromise immune function.     

Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of "particulates (insoluble) not otherwise classified" (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain "overload" over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO(2) to the hilar lymph nodes than with BaSO(4). It was also found that clearance of TiO(2) was retarded whereas clearance of BaSO(4) was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as "overload" in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO(2) caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO(4). These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).     

The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats.

We studied the effect of oral ascorbic acid treatment on nickel sulfate-induced lipid peroxidation in the liver of Wistar strain male albino rats. Lipid peroxide and glutathione levels and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in liver. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased glutathione, SOD, CAT, and GSH-Px activities in liver. The simultaneous administration of ascorbic acid with nickel sulfate resulted in a remarkable improvement of lipid peroxide, glutathione, SOD, CAT, and GSH-Px status in liver in comparison with rats treated with nickel alone. Nickel sulfate has an adverse effect on hepatic lipid peroxidation in animals, but simultaneous treatment with ascorbic acid offers a relative protection against nickel-induced hepatotoxicity.     

Comparison of ascorbic acid and ascorbic acid 2-O-alpha-glucoside on the cytotoxicity and bioavailability to low density cultures of fibroblasts.

Ascorbic acid 2-O-alpha-glucoside (AA-2G) is a stable ascorbate derivative which has vitamin C activity in vivo and in vitro. We studied whether AA-2G exerts a prooxidant action in cultured fibroblasts from chick embryo and human skin, as does ascorbic acid. At concentrations of 0.1-1.0 mM, ascorbic acid markedly reduced the viable cell number of low density cultures within 24 hr, whereas AA-2G had no such effect. The ascorbate cytotoxicity was dependent on the cell density at the time of its addition and it was characteristic of low density cultures. This cytotoxicity was completely prevented by catalase and partially by an Fe3+ ion chelator, desferrioxamine. In the early culture stage at which a morphological change in the fibroblasts began to occur, intracellular ascorbate concentrations in low density cultures after addition of ascorbic acid were much higher than in high density cultures. However, at the same concentrations, AA-2G did not cause an elevation even in low density cultures and it was also effective on collagen synthesis at high and medium densities. These results suggest that the abnormally accumulated ascorbic acid in the cells cultured at low density possibly amplifies the generation of oxygen radicals through the reduction of Fe3+ ions and subsequent oxidative reactions, leading to cell death. Therefore, it is concluded that AA-2G which supplies an adequate amount of ascorbic acid during culture period is a bioavailable ascorbate source without cytotoxicity.     

Effects of ascorbic acid and alpha-tocopherol on arsenic-induced oxidative stress

Arsenic is an ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress. Therefore, the present study was designed to determine whether supplementation of alpha-tocopherol (400 mg/kg body weight) and ascorbic acid (200 mg/kg body weight) to arsenic-intoxicated rats (100 ppm in drinking water) for 30 days affords protection against the oxidative stress caused by the metalloid. The arsenic-treated rats showed elevated levels of lipid peroxide, decreased levels of non-enzymatic antioxidants and activities of enzymatic antioxidants. Administration of alpha-tocopherol and ascorbic acid to arsenic-exposed rats showed a decrease in the level of lipid peroxidation (LPO) and enhanced levels of total sulfhydryls, reduced glutathione, ascorbic acid and alpha-tocopherol and so do the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase to near normal. These findings suggest that alpha-tocopherol and ascorbic acid prevent LPO and protect the antioxidant system in arsenic-intoxicated rats.