Formaldehyde-induced Toxicity Research Articles

Effect of fish oil supplementation on histological changes, apoptosis and oxidative stress of rat placenta against formaldehyde-induced toxicity

Formaldehyde (FA) as a common organic compound has been shown to cause placental dysfunction and fetal defects. The potential benefits of fish oil (FOil) in protecting placental structures are attributed to its antioxidant properties. This study aimed to explore the preventive role of FOil in mitigating the adverse effects of FA in pregnant rats. Thirty pregnant Wistar rats were randomly categorized into five groups of control, sham (Normal saline; Orally and intraperitoneally), FOil (0.5 ml/day; Orally), FA (5 mg/kg/bw; intraperitoneally), FA+FOil. The treatment period was from day 0–20 of pregnancy. On the 20th day of pregnancy, placental morphometric parameters were measured. The histological and histochemical analyses were performed using H&E and PAS staining, respectively. Also, the placenta tissue was analyzed for oxidative stress biomarkers, p-53 protein levels, and the expression of caspase-3 gene. The administration of FA led to a significant decrease in the weight, diameter, and thickness of the placenta, as well as a decrease in the thickness of the decidua layer, junctional and labyrinth zone, and the number of trophoblast giant cells in rat placentas. FA led to a significant increase in placental p-53 protein levels, caspase-3 expression, and oxidative stress biomarkers. Administration of FOil to pregnant rats treated with FA led to a significant decrease in morphometric and histological changes, oxidative stress, and the expression of genes associated with apoptosis. The findings suggest that the administration of FOil to FA-treated pregnant rats can protect placental histopathological changes by enhancing the activity of the antioxidant enzymes.

Fennel Seed Oil's Protective effect on Serum Potassium and Sodium Ions from Formaldehyde-Induced Toxicity in Wistar Rats

Fennel Seed Oil's Protective effect on Serum Potassium and Sodium Ions from Formaldehyde-Induced Toxicity in Wistar Rats

Astragalus polysaccharide protects formaldehyde-induced toxicity by promoting NER pathway in bone marrow mesenchymal stem cells.

In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity. Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 μmol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 μg/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA), xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot. Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 μg/mL APS. Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.

Small interfering RNA targeting of peroxiredoxinⅡ gene enhances formaldehyde-induced toxicity in bone marrow cells isolated from BALB/c mice

BackgroudsFormaldehyde (FA) is an important chemicals that can induce sick house syndrome and may be an incentive of childhood leukemia, however the exact mechanism is unclear. Oxidative stress may be an underlying reason of cancer occurring, while diverse antioxidants can protect the bone marrow cells (BMCs) from damaged. PeroxiredoxinⅡ (PrxⅡ) is an important member of the peroxiredoxin family, can remove reactive oxygen species (ROS), and is closely related with the occurrence of tumor. The present study aimed to detect a possible relationship between PrxⅡ gene and FA-induced bone marrow toxicity. MethodsThe BMCs were taken out from BALB/c mice, then exposed to control and different doses of FA (50, 100, 200 μmol/L). The cell viability, ROS level and expressions of PrxⅡ gene were examined. Afterwards, we used a small interfering RNA (siRNA) to inhibit the expression of PrxⅡ gene, and chose 100 μmol/L FA for exposure dose, to examine the cell viability, ROS level, cell cycle, apoptotic rate, expressions of PrxⅡ gene in BMCs. ResultsAfter a 24 h exposure to different doses of FA, the cell viability, expressions of PrxⅡ gene were decreased with the increasing of FA concentration, while the ROS level was increased. Inhibiting PrxⅡ gene's expression could enhance above FA-induced events. Additionally, siRNA targeting of PrxⅡcould aggravate cell cycle arrest to inhibit cell's growth and development, as well as increase apoptotic rates induced by FA. ConclusionThese results demonstrated that PrxⅡ gene was involved in FA-induced bone marrow toxicity, and siRNA targeting of PrxⅡcould enhance this toxic process.

Curcumin Prevents Renal Dysfunction, Proteinaceous and Granular Cast Formation in Tubular Lumen in Kidney of Mice Exposed to Formaldehyde Inhalation

Formaldehyde is a volatile chemical compound that is commonly used in the chemical industry. Formaldehyde inhalation exposure has been associated with cancer, respiratory diseases, digestive and neurological disorders. Oxidative stress is one of the potential mechanisms by which formaldehyde inhalation induces toxicity. Curcumin is a natural compound endowed with antioxidant properties and my thus prevent formaldehyde-induced toxicity. This study aimed to examine the effects of formaldehyde inhalation on renal function and kidney structure of mice; the potential protective effects of curcumin administration against kidney dysfunction, renal damage and oxidative stress were also investigated. Formaldehyde inhalation induced renal dysfunction and damage, as shown by the increase of serum creatinine and blood urea nitrogen levels, and caused histological damage associated with proteinaceous and granular cast formation in renal tubular lumen. The activity of antioxidant enzymes remained unchanged and malondialdehyde levels increased in a discrete and statistically non-significant way. Curcumin treatment prevented the above-described alterations by preventing an increase in renal dysfunction and changes in the kidney structure of mice. Therefore, curcumin can be a potentially useful treatment against the effects induced by exposure to gaseous pollutants such as formaldehyde in distal organs.

The effect of aqueous extract of Rosa damascena on formaldehyde-induced toxicity in mice testes

Context: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower’s oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage.Objective: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage.Materials and methods: Forty-eight adult NMRI male mice were randomly assigned to six groups (n = 8): control (normal saline, 10 mg/kg); RD40 (40 mg/kg, p.o.); FA treated (10 mg/kg of 10%, i.p.) and FA + RD treated at 10, 20 and 40 mg/kg (FA + RD10), (FA + RD20) and (FA + RD40), respectively, for 40 days. At the end of treatment regimes, serum testosterone (T) level and the reproductive activity, viz. body/organ weights, testicular structure and sperm characteristics were studied.Results: Formaldehyde administration significantly decreased serum T level (p < 0.001), testicular weight/volume, tubular diameter and sperm characteristics compared to the control group (p < 0.05). RD (40 mg/kg) administration in FA-treated mice significantly improved serum T level, testicular weight/histological structure, tubular diameter, Leydig cell number and epididymal sperm characteristics in comparison to its lower doses and the control group (p < 0.05).Discussion and conclusions: We may conclude that RD flower extract can withstand effects of FA in the male reproductive system of mice possibly due to its antioxidative properties.

Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats.

This experimental study aimed to investigate the protective effect of a bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological and behavioral outcomes in pregnant rats and developmental aspects in their offspring. Female Wistar rats were subjected to perigestational exposure to FA (2 mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os). Pregnant rats were weighed throughout gestation and tested in two behavioral paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and 19 to evaluate the anxiety-like behavior and locomotive alterations. Another subset of rats was decapitated at GD19 to determine the hematological profile along with cortisol, 17β-estradiol, and progesterone plasma levels. Reproductive and fetal measures and observations were also performed to check for developmental deformities. Significant body weight loss, hemato-immune decline, hormonal changes, anxiety and lethargy signs, locomotor disabilities, reproductive failure and fetal weight decrease were observed in FA-exposed rats. Treatment with HP alleviated the reproductive and fetal weight defects. Its behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some hematological parameters, decreased cortisol levels and increased 17β-estradiol rates. A potential preventive impact of HP was found against FA toxicity in pregnant rats.

Formaldehyde-induced toxicity in the nasal epithelia of workers of a plastic laminate plant.

Formaldehyde is a ubiquitous volatile organic compound widely used for various industrial purposes. Formaldehyde was reclassified by the International Agency for Research on Cancer as a human carcinogen, based on sufficient evidence for a casual role for nasopharyngeal cancer. However, the mechanisms by which this compound causes nasopharyngeal cancer are not completely understood. Therefore, we have examined the formaldehyde-induced toxicity in the nasal epithelia of the workers of a plastic laminate plant in Bra, Cuneo, Piedmont region, North-Western Italy, hence in the target site for formaldehyde-related nasal carcinogenesis. We have conducted a cross-sectional study aimed at comparing the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in 50 male exposed workers and 45 male controls using 32P-DNA post-labeling. The personal levels of formaldehyde exposure were analysed by gas-chromatography mass-spectrometry. The smoking status was estimated by measuring the concentrations of urinary cotinine by gas-chromatography mass-spectrometry. The air monitoring results showed that the exposure levels of formaldehyde were significantly greater for the plastic laminate plant workers, 211.4 ± 14.8 standard error (SE) μg m-3, than controls, 35.2 ± 3.4 (SE) μg m-3, P < 0.001. The levels of urinary cotinine were 1064 ± 118 ng ml-1 and 14.18 ± 2.5 ng ml-1 in smokers and non-smokers, respectively, P < 0.001. The M1dG adduct frequency per 108 normal nucleotides was significantly higher among the workers of the plastic laminate plant exposed to formaldehyde, 111.6 ± 14.3 (SE), compared to controls, 49.6 ± 3.4 (SE), P < 0.001. This significant association persisted also when personal dosimeters were used to measure the extent of indoor levels of formaldehyde exposure. No influences of smoking and age were observed across the study population. However, after categorization for occupational exposure, a significant effect was found in the controls, P = 0.018, where the levels of DNA damage were significantly correlated with the levels of urinary cotinine, regression coefficient (β) = 0.494 ± 0.000 (SE), P < 0.002. Our findings indicated that M1dG adducts constitute a potential mechanism of formaldehyde-induced toxicity. Persistent DNA damage contributes to the general decline of the physiological mechanisms designed to maintain cellular homeostasis.

The effect of proanthocyanidin on formaldehyde-induced toxicity in rat testes.

This study investigated the effect of proanthocyanidin (PA) against formaldehyde (FA)-induced lipid peroxidation damage and morphological changes in rat testes. Twenty-one Wistar albino rats were randomized into 3 groups: control, FA, and FA + PA groups. Plasma and tissue malondialdehyde (MDA) and total sialic acid (TSA) levels were measured. Testes tissues were observed by light and electron microscopy. TSA (plasma and tissue) levels decreased and MDA (plasma) significantly increased (P < 0.05) in rats treated with FA compared to the controls. Tissue MDA levels were not significantly different. Several necrotic changes were observed in testes tissues by light and electron microscopy. Disordering in epithelia of seminiferous tubules, vacuolization between germinal epithelium cells, and separated basement membranes were observed by light microscope. Immunopositivity in Leydig cells decreased in the FA group (P < 0.05). In the FA + PA group there were more immune Leydig cells reacting immune-positively than in the FA group (P < 0.05). Ultrastructurally, FA also caused disorganization and loss of mitochondrial cristae, and dilatation in endoplasmic reticulum in testes. The results suggest that PA has a protective effect on FA toxicity in testes.

BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells

Formaldehyde (FA) is a common environmental contaminant that has toxic effects on the central nervous system (CNS). Our previous data demonstrated that hydrogen sulfide (H2S), the third endogenous gaseous mediator, has protective effects against FA-induced neurotoxicity. As is known to all, Brain-derived neurotropic factor (BDNF), a member of the neurotrophin gene family, mediates its neuroprotective properties via various intracellular signaling pathways triggered by activating the tyrosine kinase receptor B (TrkB). Intriguingly, our previous data have illustrated the upregulatory role of H2S on BDNF protein expression in the hippocampus of rats. Therefore, in this study, we hypothesized that H2S provides neuroprotection against FA toxicity by regulating BDNF-TrkB pathway. In the present study, we found that NaHS, a donor of H2S, upregulated the level of BDNF protein in PC12 cells, and significantly rescued FA-induced downregulation of BDNF levels. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, markedly reversed the inhibition of NaHS on FA-induced cytotoxicity and ablated the protective effects of NaHS on FA-induced oxidative stress, including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA). We also showed that K252a abolished the inhibition of NaHS on FA-induced apoptosis, as well as the activation of caspase-3 in PC12 cells. In addition, K252a reversed the protection of H2S against FA-induced downregulation of Bcl-2 protein expression and upregulation of Bax protein expression in PC12 cells. These data indicate that the BDNF-TrkB pathway mediates the neuroprotection of H2S against FA-induced cytotoxicity, oxidative stress and apoptosis in PC12 cells. These findings provide a novel mechanism underlying the protection of H2S against FA-induced neurotoxicity.

Effect of Ginkgo Biloba Leaves Extract on Some Formaldehyde Induced Toxicity in hippocampus of Adult Male Albino Rats

Formaldehyde (FA) heavily impacts the everyday consumer products. It is widely used in the construction, textile, furniture, medical, chemical, and pharmaceutical industries. Exposure to FA poses a significant threat to public health. It can cause severe central nervous system impairment. Extract from the leaves of Ginkgo biloba exerts a novel spectrum of biological, pharmacological and therapeutic properties against oxidative stress, so it was of special concern to investigate the role of Ginkgo biloba leaves extract (GBE) on the neurotoxic effects of FA on hippocampus of adult male albino rats. Thirty adult male albino rats were used in the present study. They were divided into 5 equal groups: Group I negative control, Group II received distilled water by intraperitoneal (i.p.) injection. Group III received GBE (300 mg/kg/day) orally. Group IV received FA (0.2 mg/kg/day i.p. and Group V received 0.2 mg/kg FA + 300 mg/kg GBE. After the end of the study ( 4weeks), all rats were sacrificed and brain were dissected out and hippocampus subjected to estimation of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) catalase (CAT) and malondialdehyde (MDA) levels. Histological examination of the hippocampus and immunohistochemical staining for Glial fibrillary acidic protein (GFAP) were also done. The results of this study revealed that, the levels of SOD, CAT and GSH-Px were significantly decreased, while MDA level in hippocampus tissue were significantly increased in rats treated with FA compared to those of the controls. Microscopic examination of neurons of the hippocampus in this group revealed picnotic nuclei, vacuolar degeneration and neuronal loss. Immunostaining showed areas with significantly increased GFAP immunopositivity. Concomitant administration of GBE with FA resulted in a significant increase in antioxidant enzymes activity (SOD, GSH-Px and CAT), decreased MDA, and improvement of histopathological changes induced by FA. Also a significant reduction in expression of GFAP was observed. It was concluded that short term administration of FA induced neurotoxicity on the hippocampus of adult male albino rats, with oxidant stress and lipid peroxidation which may be a molecular mechanism involved in FA induced neurotoxicity. Furthermore, these effects were decreased by the concomitant use of GBE. It is recommended to use GBE for amelioration of toxic manifestations of formaldehyde in exposed population.

Formaldehyde and Epigenetic Alterations: MicroRNA Changes in the Nasal Epithelium of Nonhuman Primates

Background: Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it is imperative to understand the mechanisms underlying formaldehyde-induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde. Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disruptions in miRNA expression profiles in vitro.Objectives: Using an in vivo model, we set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates.Methods: Cynomolgus macaques were exposed by inhalation to approximately 0, 2, or 6 ppm formaldehyde for 6 hr/day for 2 consecutive days. Small RNAs were extracted from nasal samples and assessed for genome-wide miRNA expression levels. Transcriptional targets of formaldehyde-altered miRNAs were computationally predicted, analyzed at the systems level, and assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR).Results: Expression analysis revealed that 3 and 13 miRNAs were dysregulated in response to 2 and 6 ppm formaldehyde, respectively. Transcriptional targets of the miRNA with the greatest increase (miR-125b) and decrease (miR-142-3p) in expression were predicted and analyzed at the systems level. Enrichment was identified for miR-125b targeting genes involved in apoptosis signaling. The apoptosis-related targets were functionally tested using RT-PCR, where all targets showed decreased expression in formaldehyde-exposed samples.Conclusions: Formaldehyde exposure significantly disrupts miRNA expression profiles within the nasal epithelium, and these alterations likely influence apoptosis signaling.

The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human lymphoblastoid cell lines

Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen. The major mode of action of FA is thought to be the formation of DNA-protein cross-links (DPCs). Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway are limited, particularly in human hematopoietic cells. Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA-induced toxicity in human lymphoblast cell models of FANCD2 deficiency (PD20 cells) and FANCD2 sufficiency (PD20-D2 cells). After treatment of the cells with 0-150 μM FA for 24 h, DPCs were increased in a dose-dependent manner in both cell lines, with greater increases in FANCD2-deficient PD20 cells. FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose-dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells. Increased levels of γ-ATR and γ-H2AX in both cell lines suggested the recognition of FA-induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially reducing the capacity to repair DPCs. Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity. Future studies are needed to delineate the role of this pathway in mitigating FA-induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia.

Chemoprotective effects of antioxidants against formaldehyde-induced toxicity in human keratinocytes

Chemoprotective effects of antioxidants against formaldehyde-induced toxicity in human keratinocytes

Identification of formaldehyde-responsive genes by suppression subtractive hybridization

Formaldehyde is frequently used in indoor household and occupational environments. Inhalation of formaldehyde invokes an inflammatory response, including a variety of allergic signs and symptoms. Therefore, formaldehyde has been considered as the most prevalent cause of sick building syndrome, which has become a major social problem, especially in developing urban areas. Further formaldehyde is classified as a genotoxicant in the respiratory tract of rats and humans. To better understand the molecular mechanisms involved in formaldehyde intoxication, we sought differentially regulated genes by formaldehyde exposure to Hs 680.Tr human trachea cells, using polymerase chain reaction (PCR)-based suppression subtractive hybridization. We identified 27 different formaldehyde-inducible genes, including those coding for the major histocompatibility complex, class IA, calcyclin, glutathione S-transferase pi, mouse double minute 2 (MDM2), platelet-derived growth factor receptor alpha, and which are known to be associated with cell proliferation and differentiation, immunity and inflammation, and detoxification. Induction of these genes by formaldehyde treatment was confirmed by reverse transcription PCR and western blot analysis. Further, the expression of calcyclin, glutathione S-transferase pi, PDGFRA and MDM2 were significantly induced in the tracheal epithelium of Sprague Dawley rats after formaldehyde inhalation. Our results suggest that the elevated levels of these genes may be associated with the formaldehyde-induced toxicity, and that they deserve evaluation as potential biomarkers for formaldehyde intoxication.

Histochemical localization of formaldehyde dehydrogenase in the rat

Formaldehyde dehydrogenase (FDH) activity has been demonstrated biochemically in the olfactory and respiratory mucosae and in the liver of the rat, but the cellular localization of this enzyme has not been investigated. A histochemical procedure was developed to permit cellular localization of FDH. This allowed us to examine the relationship between distribution of FDH and formaldehyde-induced toxicity. Cold-processed glycol methacrylate embedded tissues were used to localize FDH activity in the rat respiratory tract, kidney, liver, and brain. Five- or tenmicrometer tissue sections were incubated in a reaction mixture containing formaldehyde (HCHO), glutathione (GSH), NAD +, nitroblue tetrazolium, pyrazole, and disulfiram. A blue formazan precipitate was formed at the site of FDH activity. Epithelial cell cytoplasm of both the respiratory and the olfactory mucosae of the nose stained for FDH, and olfactory sensory cell nuclei were also positive. Underlying Bowman's and seromucous glands were weakly positive. The lung had FDH activity located mainly in the Clara cells of the airways, with only diffuse weak activity in the lung parenchyma. Liver had activity in the cytoplasm of the hepatocytes, while in the kidney FDH was most prominent in the brush border of the P2 segment of the proximal tubules. Brain white matter stained strongly for FDH, while in gray matter only the neuropil exhibited weak activity. Corresponding tissue sections were stained for sulfhydryls; these sections indicated that GSH is likely to be present in all cells with FDH activity. For the respiratory tract these results demonstrate distinct differences between the location of FDH activity and previously reported nonspecific aldehyde dehydrogenase activity in the nose ( M. S. Bogdanffy, H. W. Randall, and K. T. Morgan, 1986, Toxicol. Appl. Pharmacol. 82, 560–567). While high aldehyde dehydrogenase activities were found in tissues with low toxicities due to acetaldehyde exposure and vice versa, FDH activity was observed in tissues whether or not they exhibited a toxic response to inhaled HCHO. While not able to account for the localized toxicity of HCHO, the presence of FDH and glutathione in the epithelial layer of the nasal cavity presents a barrier to inhaled formaldehyde at low concentrations and may partially explain the observed nonlinearity of HCHO toxicity.

Interaction of formaldehyde with glutathione in the isolated/ventilated perfused lung and the isolated perfused liver.

The interaction of formaldehyde (CH2O) with reduced glutathione (GSH) was evaluated in aqueous solution and in isolated perfused lungs and livers. Addition of CH2O (0-4.9 mM) to a solution of 0.17 mM GSH in 2 mM EDTA, pH 7.4, resulted in a time- and concentration-dependent depletion of GSH. Perfusion of livers with fortified Krebs-Ringer bicarbonate buffer containing 0.3-4.9 mM CH2O resulted in a dose-dependent depletion of GSH. Perfusion of isolated ventilated lungs with perfusate containing 4.9 mM CH2O resulted in a depletion of GSH to 75% of controls. However, lower concentrations of CH2O in the lung perfusate did not result in depletion of GSH. These results demonstrate that exposure to CH2O in aqueous solution or in the perfused lung and liver is capable of depleting endogenous GSH. However, the concentrations of CH2O required to yield a significant depletion of endogenous GSH exceed those encountered in vivo. Thus, it is unlikely that depletion of GSH by CH2O is a causal factor in formaldehyde-induced toxicity.