Toxic Formaldehyde Research Articles

Inhibition of ALDH2 protects PC12 cells against formaldehyde-induced cytotoxicity: involving the protection of hydrogen sulphide.

Formaldehyde (FA), a common environmental contaminant, has toxic effects on the central nervous system (CNS). We have previously found that hydrogen sulphide (H2 S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA. However, the underlying mechanism is poor. Aldehyde-dehydrogenase-2 (ALDH2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H2 S antagonizes FA-induced neurotoxicity by modulating ALDH2. In the present study, we found that the exposure of PC12 cells to FA causes increase in ALDH2 expression and activity. Daidzin, an inhibitor of ALDH2, significantly antagonizes FA-exerted cytotoxicity and oxidative stress including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA), in PC12 cells. We also showed that daidzin markedly attenuated FA-induced apoptosis in PC12 cells. Furthermore, we found that H2 S reverses FA-elicited upregulation of ALDH2 in PC12 cells. Our results demonstrated the involvement of downregulation of ALDH2 in the protection of H2 S against FA neurotoxicity.

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.

Hierarchical porous nitrogen-doped partial graphitized carbon monoliths for supercapacitor

Porous carbon monoliths have attracted great interest in many fields due to their easy availability, large specific surface area, desirable electronic conductivity, and tunable pore structure. In this work, hierarchical porous nitrogen-doped partial graphitized carbon monoliths (N–MC–Fe) with ordered mesoporous have been successfully synthesized by using resorcinol-formaldehyde as precursors, iron salts as catalyst, and mixed triblock copolymers as templates via a one-step hydrothermal method. In the reactant system, hexamethylenetetramine (HMT) is used as nitrogen source and one of the carbon precursors under hydrothermal conditions instead of using toxic formaldehyde. The N–MC–Fe show hierarchically porous structures, with interconnected macroporous and ordered hexagonally arranged mesoporous. Nitrogen element is in situ doped into carbon through decomposition of HMT. Iron catalyst is helpful to improve the graphitization degree and pore volume of N–MC–Fe. The synthesis strategy is user-friendly, cost-effective, and can be easily scaled up for production. As supercapacitors, the N–MC–Fe show good capacity with high specific capacitance and good electrochemical stability.

Improving physical and mechanical properties of new lignin- urea-glyoxal resin by nanoclay

To eliminate toxic formaldehyde from wood based panels, glyoxal, a low volatility and nontoxic aldehyde, was used to react with urea and lignin to prepare a glyoxalated lignin- urea-glyoxal (LUG) wood adhesive resin. Moreover, another objective of this research work was to improve the physical and mechanical properties of the new LUG resins by nanoclay addition. For the preparation of LUG resin, glyoxalated lignin (15 mass%) was added instead of second urea to the urea-glyoxal resin synthesis under acid conditions. The LUG resin so prepared was mixed with 1, 2 and 3 mass% nanoclay by mechanically stirring for 5 min at room temperature. Then, the physicochemical and structural properties of the prepared resins as well as the water absorption and the mechanical properties of the plywood panels bonded with it were measured according to standard methods. The physicochemical test results indicated that the gel time of the LUG resin was markedly slower than that of the UF resin. Plywood panels prepared with the LUG resin also presented lower water absorption as well as weaker shear strength than those prepared with the UF resin. Addition of nanoclay changed the physicochemical properties of the resins as the gelation time of the LUG resin was shorter when adding sodium montmorillonite (NaMMT). Higher shear strength values and lower water absorption were achieved by continuously increasing nanoclay proportion from 1 to 3 mass%. Furthermore, addition of nanoclay had more influence on panels bending strength than their flexural modulus. X-ray diffraction (XRD) analysis also indicated that NaMMT exfoliated completely when mixed with LUG resin.

A Single-Center Open-Label Single-Arm Study Evaluating Efficacy and Safety of Skin Adhesive Epinexus<sup>TM</sup> in Surgical Patients

Existing skin adhesives may, however, cause inflammatory response to toxicity of formaldehyde generated as hydrolysate of polycyanoacrylate (the main ingredient), delay in wound closure due to the adhesive’s flowing into the wound from the edges, or a wide scar. EpinexusTM (Mitsui Chemicals, Inc.), the skin adhesive used for this study, was developed to prevent these risks. For the method of this study, This was a single-center, open-label, single-arm, intervention study of an acrylate skin adhesive, EpinexusTM. The primary endpoint was safety. The secondary endpoints were wound closure, cosmetic outcome (Manchester Scar Scale), and usability. Failures and adverse events were also appropriately evaluated. As a result, there were no particular adverse events such as inflammatory findings, which demonstrated that there is no problem in safety. Some common adverse events were observed, but no adverse events for which a causal relationship cannot be ruled out or failures. As a conclusion, there was no problem in wound closure, cosmetic outcome, or usability. This was a pilot study of EpinexusTM of an ongoing, single-center, open-label, parallel-group, comparative study in 60 subjects comparing EpinexusTMwith an existing skin adhesive, Dermabond&reg Advanced.

The Effect of Chrysin on Liver Damage Induced By Subchronic Toxicity of Formaldehyde in Rats

The Effect of Chrysin on Liver Damage Induced By Subchronic Toxicity of Formaldehyde in Rats

Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 μg Vit E, or 1.5 mg/kg + 0.1 μg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 μmol/L FA, 25 μmol/L FA, 50 μmol/L FA, 10 mg/L Vit. E, and 50 μmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 μg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

DFT study on the chemical sensing properties of B24N24 nanocage toward formaldehyde

It has been previously shown that the toxic formaldehyde gas (H2CO) cannot be detected by pristine BC2N, carbon, and BN nanotubes, BC3 nanosheet and graphene. Herein, density functional theory calculations were employed to investigate the electronic and structural behavior of a pristine B24N24 nanocluster toward H2CO molecules. It was found that [4,6] BN bonds of the nanocluster are the most favorable sites for the H2CO adsorption, compared to the [4,8], and [6,8] ones. When an H2CO molecule is adsorbed on a [4,6] BN bond, an energy of about 16.40kcal/mol is released and the HOMO-LUMO gap of the cluster is decreased from 6.45 to 2.98eV. Thus, the electrical conductivity of the cluster is significantly increased, indicating that it can produce an electronic noise at the presence of H2CO molecules. Increasing the number of adsorbed H2CO molecules, the electrical conductivity more increases. The recovery time for the H2CO from the surface of B24N24 is calculated to be very short (∼1.02s). Also, the UV–vis spectrum shows that the λmax of the B24N24 shows a large redshift upon the adsorption process and transfers from the UV to the visible region.

Interlaboratory Precision of Acute Toxicity Tests Using Reference Toxicant Formaldehyde

Acute toxicity test, which takes place among rapid toxicity tests and is conducted through bioluminescent bacteria, has been included in many countries' standards thanks to its test duration, sample volume, cost-efficiency and result sensitivity. Sensitivity of Microtox® Reagent, being one of the commercial kits of bioluminescent bacteria, can be detected via reference toxicants (control). Various reference toxicants (control) are recommended by the manufacturer company to be used in Microtox® acute toxicity test. This study aims to use formaldehyde as alternative reference toxicant (control) in Microtox® acute toxicity test. Acute toxicity of formaldehyde, according to Vibrio fischeri, was investigated on 5, 15 and 30 minutes of inhibition periods. EC 50 values were found as 2,30±0,60 mg/l; 2,14±0,63 mg/l and 2,17±0,70 mg/l by inhibition periods, respectively. Standard deviation of EC 50 values found for each sample group differed between 0,01-0,47. According to mean acute toxicity results of all formaldehyde inhibition periods, 0,10 unit deviation was found in 5 minutes of results. For 15 and 30 minutes of inhibition periods, mean value of unit deviation was found as 0,06 and 0,04 which showed closer values to each other and the mean value. The investigated toxicants show the performance of pipetting sensitivity of reagent, analyzer and test operator.

Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast.

Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

The toxicity of continuous long-term low-dose formaldehyde inhalation in mice

Although the toxicity of high-dose formaldehyde (FA) inhalation has been extensively analyzed in animals, the effect of continuous long-term exposure to low-dose FA has not been well documented. This study aims to evaluate the toxicity of continuous long-term low-dose FA inhalation in mice. Forty-eight Kunming male mice were equally randomized to three groups according to the dose of FA inhalation exposure: a control (0 mg/m3) group, a low-dose (0.08 mg/m3) group and a high-dose (0.8 mg/m3) group. The mice have been selected to expose to FA for different consecutive days at 24 h/day. The learning and memory functions, pathological changes in the lung and liver, and the percentage of CD4 + T and CD8 + T cells were observed and analyzed. It was found that continuous long-term inhalation of FA at relatively low doses could impair the learning and memory functions and induce pathological changes in the lung and liver, but did not seem to significantly affect the number of immune (CD4 + T and CD8 + T) cells.

Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure

Low-level formaldehyde exposure is inevitable in industrialized countries. Although daily-life formaldehyde exposure level is practically impossible to induce cell death, most of mechanistic studies related to formaldehyde toxicity have been performed in cytotoxic concentrations enough to trigger cell death mechanism. Currently, toxicological mechanisms underlying the sub-cytotoxic exposure to formaldehyde are not clearly elucidated in skin cells. In this study, the genome-scale transcriptional analysis in normal human keratinocytes (NHKs) was performed to investigate cutaneous biological pathways associated with daily life formaldehyde exposure. We selected the 175 upregulated differentially expressed genes (DEGs) and 116 downregulated DEGs in NHKs treated with 200μM formaldehyde. In the Gene Ontology (GO) enrichment analysis of the 175 upregulated DEGs, the endoplasmic reticulum (ER) unfolded protein response (UPR) was identified as the most significant GO biological process in the formaldeyde-treated NHKs. Interestingly, the sub-cytotoxic formaldehyde affected NHKs to upregulate two enzymes important in the cellular transsulfuration pathway, cystathionine γ-lyase (CTH) and cystathionine-β-synthase (CBS). In the temporal expression analysis, the upregulation of the pro-inflammatory DEGs such as MMP1 and PTGS2 was detected earlier than that of CTH, CBS and other ER UPR genes. The metabolites of CTH and CBS, l-cystathionine and l-cysteine, attenuated the formaldehyde-induced upregulation of pro-inflammatory DEGs, MMP1, PTGS2, and CXCL8, suggesting that CTH and CBS play a role in the negative feedback regulation of formaldehyde-induced pro-inflammatory responses in NHKs. In this regard, the sub-cytotoxic formaldehyde-induced CBS and CTH may regulate inflammation fate decision to resolution by suppressing the early pro-inflammatory response.

Effects of formaldehyde intoxication on liver of Swiss albino mice

Formaldehyde (FA) is a very reactive one-carbon compound, can react with lipids, proteins, and nucleic acids which are cellular components.FA induces cellular toxic effects in the liver by damaging hepatic parenchyma and impairment of functions. This study was carried out to evaluatethe serum biochemical changes and cytotoxic effects on liver in Swiss albino mice caused by FA toxicity. For this purpose, mice were divided into threeequal groups i.e. Control, oral andintraperitoneal.Oral and intraperitonealgroups were further divided into three subgroups which were subjected to exposure of FA for 30 and 10 consecutive days respectively. After exposure, blood and liver samples were collected and analyzed for biochemical and morphological studies. The serum biochemical parameters like Aspartate Transaminase (AST) and Alanine Transaminase (ALT) were increased significantly (P‹0.05) in mice after FA exposure. The anatomical results revealed gross morphological changes i.e. congestion and petechial hemorrhages on the liver. Histologically, the liver showedscattered lymphocytic infiltration, dilatation of sinusoids, necrosis and degeneration of parenchymatous cells in orally exposed mice (10 mg/kg) and diffuse lymphocytic infiltration, necrosis were seen in intraperitoneallyFA injectedmice at the rate of 7 and 10 mg/kg body weight.All these findings revealed that, FA depending on specific dose leads to an irritant toxic effects on the liver of mice. Keywords:Formaldehyde, Histomorphology, Liver, Mice, Serum biochemical test.

Comparison of inhaled and intraperitoneal formaldehyde toxicity in rats and the evaluation of the effects of melatonin

52nd Congress of the European-Societies-of-Toxicology (EUROTOX) -- SEP 04-07, 2016 -- Seville, SPAIN

Formaldehyde induces toxicity in mouse bone marrow and hematopoietic stem/progenitor cells and enhances benzene-induced adverse effects.

Formaldehyde (FA) is a human leukemogen and is hematotoxic in human and mouse. The biological plausibility of FA-induced leukemia is controversial because few studies have reported FA-induced bone marrow (BM) toxicity, and none have reported BM stem/progenitor cell toxicity. We sought to comprehensively examine FA hematoxicity in vivo in mouse peripheral blood, BM, spleen and myeloid progenitors. We included the leukemogen and BM toxicant, benzene (BZ), as a positive control, separately and together with FA as co-exposure occurs frequently. We exposed BALB/c mice to 3mg/m3 FA in air for 2weeks, mimicking occupational exposure, then measured complete blood counts, nucleated BM cell count, and myeloid progenitor colony formation. We also investigated potential mechanisms of FA toxicity, including reactive oxygen species (ROS) generation, apoptosis, and hematopoietic growth factor and receptor levels. FA exposure significantly reduced nucleated BM cells and BM-derived colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E); down-regulated GM-CSFRα and EPOR expression; increased ROS in nucleated BM, spleen and CFU-GM cells; and increased apoptosis in nucleated spleen and CFU-GM cells. FA and BZ each similarly altered BM mature cells and stem/progenitor counts, BM and CFU-GM ROS, and apoptosis in spleen and CFU-GM but had differential effects on other end points. Co-exposure was more potent for several end points. Thus, FA is toxic to the mouse hematopoietic system, including BM stem/progenitor cells, and it enhances BZ-induced toxic effects. Our findings suggest that FA may induce BM toxicity by affecting myeloid progenitor growth and survival through oxidative damage and reduced expression levels of GM-CSFRα and EPOR.

The Effects of Ferulic Acid Against Oxidative Stress and Inflammation in Formaldehyde-Induced Hepatotoxicity.

This study was designed to elucidate the protective effects of ferulic acid (FA) on formaldehyde-induced hepatotoxicity by measuring some routine biochemical parameters, cytokine levels, and oxidative stress-related parameters in addition to YKL-40 in male Wistar albino rats. Tissue superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities, and tissue malondialdehyde (MDA) levels were measured. Also, serum YKL-40, TNF-α, IL-6, IL-1β, IL-8, total protein, albumin, total bilirubin concentrations, and AST, ALT, ALP, and LDH activities were measured. Histological specimens were examined in light microscopy. Formaldehyde significantly increased tissue MDA, and serum cytokine levels and also decreased activities of antioxidant enzymes. FA treatment decreased MDA and cytokine levels and increased activities of antioxidant enzymes. FA also alleviated degeneration due to formaldehyde toxicity. We suggested that FA can be used as a promising hepatoprotective agent against formaldehyde toxicity because of the obvious beneficial effects on oxidative stress parameters.

Regulation of intracellular formaldehyde toxicity during methanol metabolism of the methylotrophic yeast Pichia methanolica

In this study we found that the methylotrophic yeast Pichia methanolica showed impaired growth on high methanol medium (>5%, or 1.56M, methanol). In contrast, P.methanolica grew well on glucose medium containing 5% methanol, but the growth defects reappeared on glucose medium supplemented with 5mM formaldehyde. During methanol growth of P.methanolica, formaldehyde accumulated in the medium up to 0.3mM before it was consumed rapidly based on cell growth. These findings indicate that the growth defect of P.methanolica on high methanol media is not caused directly by methanol toxicity, but rather by formaldehyde, which is a key toxic intermediate of methanol metabolism. Moreover, during methanol growth of P.methanolica, expression of enzymes in the methanol-oxidation pathway were induced before the alcohol oxidase isozymes Mod1p and Mod2p, and Mod1p expression was induced before Mod2p. These results suggest that to avoid excess accumulation of formaldehyde-the toxic intermediate of methanol metabolism-P.methanolica grown on methanol strictly regulates the order in which methanol-metabolizing enzymes are expressed.

Human nasal epithelial cells derived from multiple subjects exhibit differential responses to H3N2 influenza virus infection in vitro

Human nasal epithelial cells derived from multiple subjects exhibit differential responses to H3N2 influenza virus infection in vitro

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.

Density functional study on the adsorption of some aliphatic aldehydes on (ZnO)12 and M-doped (ZnO)12 nanocages

A theoretical study was performed on the adsorption of some aliphatic aldehydes on a Zn12O12 nanocage, concerning energetic, geometric and electronic parameters using DFT at the B3LYP and M06-2X levels. Interaction of the aldehyde molecules with the surface was analyzed by means of DOS analysis and Bader’s method. It was expected that adsorption of the examined aldehydes on the ZnO nanocage would be achieved through the interaction of the carbonyl oxygen atom with the surface Zn2+ ions. Effects of chain-length and steric congestions around the carbonyl group were inspected. The findings revealed that the adsorption energy was decreased on lengthening the aliphatic chain. Interactions between R–COH and Zn12O12 induced significant changes in the HOMO–LUMO energy gap of the nanocage. Thus, the ZnO nanocage may be used as an aldehyde sensor device, especially for the detection of toxic formaldehyde. Moreover, it was found that a V-doped nanocage can effectively interact with formaldehyde. It is believed that doping of ZnO with Ti and V effectively improves the sensitivity of the zinc oxide nanocage towards aliphatic aldehydes.