Early Recovery Process of Acute Lung Injury and Kinetics of Fluoride in Lung and Blood as the Accidental Model of Inhalation Exposure to Hydrofluoric Acid in Rats

Introduction: Hydrofluoric acid (HFA) is commonly used in chemical industries despite reports of acute lethality after occupational accident. We previously confirmed that acute death of rats after HFA aerosol inhalation can be due to pulmonary dysfunction. Although there have been several reports su...

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Published inBiomedical Research on Trace Elements Vol. 23; no. 3; pp. 202 - 207
Main Authors Dote, Tomotaro, Imanishi, Masafumi, Hayasi, Emi, Tsuji, Hiroshi, Nakayama, Shin, Kono, Koichi
Format Journal Article
LanguageEnglish
Japanese
Published Osaka Japan Society for Biomedical Research on Trace Elements 31.10.2012
Japan Science and Technology Agency
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ISSN0916-717X
1880-1404
DOI10.11299/brte.23.202

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Abstract Introduction: Hydrofluoric acid (HFA) is commonly used in chemical industries despite reports of acute lethality after occupational accident. We previously confirmed that acute death of rats after HFA aerosol inhalation can be due to pulmonary dysfunction. Although there have been several reports suggesting that respiratory disorders can be improved with specialized emergency procedures over a few days, there are currently no established protocols for emergency procedures for aerosolized HFA inhalation. It is necessary for therapy protocol to establish the experimental animal model about recovery process for the best treatment. The purpose of this study was to elucidate the process of lung recovery in rats exposed to HFA below fatal dose as the model with the occupational accident. Methods: Rats were divided into four groups: saline (1 h) group (n = 6), saline (48 h) group (n = 6), HFA (1h) group (n = 11), and HFA (48 h) group (n = 11). Rats were intratracheally sprayed with aerosols of HFA (0.36mg/kg) or saline. Blood, bronchoalveolar lavage (BALF) and lung tissue were collected at 1 h or 48 h after HFA administration. Blood gases and BALF were analyzed. The concentrations of F were measured in serum and BALF. The lung tissues were observed by light microscopy. The severities of pathohistological findings were evaluated by semi-quantative gradings in a rat from each group. Results: All rats exposed to HFA were alive 48 h later. The mean PO2 of the HFA (1 h) group was significantly lower compared with the saline (1 h) group, and mean PO2 of the HFA (48 h) group was higher compared to the HFA (1 h) group. The mean of surfactant protein-D (SP-D) level in BALF in the HFA (1 h) group was significantly lower compared to the saline (1 h) group. The mean values of SP-D and LDH in the HFA (48 h) group were significantly higher than those in the HFA (1 h) group, respectively. Means of F in serum and BALF in the HFA (1 h) group were significantly higher compared to the saline and the HFA (48 h) groups. There were no significant differences in these indices between the HFA (48 h) and saline (48 h) groups. Macroscopic swelling and hemorrhages in the lung were observed bilaterally in both HFA groups. Semi-quantitative grading of pathohistological findings indicated that perivascular and alveolar effusion into alveolar spaces were evident in the HFA (1 h) group and thickened bronchial epithelium and desquamations of bronchial epithelium were evident in the HFA (48 h) group. Discussion: The dose used in this study was not lethal. No differences between PO2 of the HFA (48 h) group and saline group (48 h) suggested that respiratory function recovered. Reduced F levels in serum and BALF indicated that HFA was rapidly absorbed from lung tissue into blood and metabolized by 48 h after administration. Perivascular and alveolar injury occurred within 1 h and thickened bronchial epithelium and desquamations of bronchial epithelium appeared 48 h later. It was suggested that the lung tissues were in recovery process from the pathohistological findings in 48 h. The experimental model of the HFA inhalation was established in this study. It would be an important step toward a possible treatment for the lung injury exposed to HFA.
AbstractList Introduction: Hydrofluoric acid (HFA) is commonly used in chemical industries despite reports of acute lethality after occupational accident. We previously confirmed that acute death of rats after HFA aerosol inhalation can be due to pulmonary dysfunction. Although there have been several reports suggesting that respiratory disorders can be improved with specialized emergency procedures over a few days, there are currently no established protocols for emergency procedures for aerosolized HFA inhalation. It is necessary for therapy protocol to establish the experimental animal model about recovery process for the best treatment. The purpose of this study was to elucidate the process of lung recovery in rats exposed to HFA below fatal dose as the model with the occupational accident. Methods: Rats were divided into four groups: saline (1 h) group (n = 6), saline (48 h) group (n = 6), HFA (1h) group (n = 11), and HFA (48 h) group (n = 11). Rats were intratracheally sprayed with aerosols of HFA (0.36mg/kg) or saline. Blood, bronchoalveolar lavage (BALF) and lung tissue were collected at 1 h or 48 h after HFA administration. Blood gases and BALF were analyzed. The concentrations of F were measured in serum and BALF. The lung tissues were observed by light microscopy. The severities of pathohistological findings were evaluated by semi-quantative gradings in a rat from each group. Results: All rats exposed to HFA were alive 48 h later. The mean PO2 of the HFA (1 h) group was significantly lower compared with the saline (1 h) group, and mean PO2 of the HFA (48 h) group was higher compared to the HFA (1 h) group. The mean of surfactant protein-D (SP-D) level in BALF in the HFA (1 h) group was significantly lower compared to the saline (1 h) group. The mean values of SP-D and LDH in the HFA (48 h) group were significantly higher than those in the HFA (1 h) group, respectively. Means of F in serum and BALF in the HFA (1 h) group were significantly higher compared to the saline and the HFA (48 h) groups. There were no significant differences in these indices between the HFA (48 h) and saline (48 h) groups. Macroscopic swelling and hemorrhages in the lung were observed bilaterally in both HFA groups. Semi-quantitative grading of pathohistological findings indicated that perivascular and alveolar effusion into alveolar spaces were evident in the HFA (1 h) group and thickened bronchial epithelium and desquamations of bronchial epithelium were evident in the HFA (48 h) group. Discussion: The dose used in this study was not lethal. No differences between PO2 of the HFA (48 h) group and saline group (48 h) suggested that respiratory function recovered. Reduced F levels in serum and BALF indicated that HFA was rapidly absorbed from lung tissue into blood and metabolized by 48 h after administration. Perivascular and alveolar injury occurred within 1 h and thickened bronchial epithelium and desquamations of bronchial epithelium appeared 48 h later. It was suggested that the lung tissues were in recovery process from the pathohistological findings in 48 h. The experimental model of the HFA inhalation was established in this study. It would be an important step toward a possible treatment for the lung injury exposed to HFA.
Author Tsuji, Hiroshi
Nakayama, Shin
Imanishi, Masafumi
Hayasi, Emi
Kono, Koichi
Dote, Tomotaro
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References [6] Pan T, Nielsen L, Allen M, Shannon K, et al: Serum SP-D is a marker of lung injury in rats. American Journal of Physiology - Lung Cell and Molecular Physiology 282: 824-32, 2002.
[10] Beck BD, Gerson B, Feldman HA: Lactate dehydrogenase isoenzymes in hamster lung lavage fluid after lung injury. Toxicol Appl Pharmaco 71: 59-71, 1983.
[7] Lund K, Refsnes M, Sandstrøm T, Søstrand P, Schwarze P, Boe J, Kongerud J: Increased CD3 positive cells in bronchoalveolar lavage fluid after hydrogen fluoride inhalation. Scand J Work Environ Health 25: 326-334, 1999.
[3] Kawaura F, Fukuoka M, Aragane N, Hayashi S: Acute respiratory distress syndrome induced by hydrogen fluoride gas inhalation. Nihon Kokyuki Gakkai Zasshi 47:991-5, 2009.
[9] Takahashi H, Sano H, Chiba H, Kuroki Y: Plumonary Surfactant Proteins A and D: Innate Immune Functions and Biomarkers for Lung Disease. Curr Pharm Des 12: 589-598, 2006.
[2] Imanishi M, Dote T, Kono K: Lethal effects on blood and lung during acute respiratory distress after inhalation exposure of rats to aerosolized hydrofluoric acid. Jpn J Occup Med Traumatol 57:109-117, 2009.
[4] Mitsui G, Dote T, Yamadori E, Adachi K. Kono K : Serum kinetics of fluoride and abnormalities of urinary parameters after single intravenous injection of hydrofluoric acid in rats. Biomed Res Trace Elem 19: 101-104, 2008.
[1] Tsonis L, Hantsch-Bardsley C, Gamelli RL: Hydrofluoric acid inhalation injury. J Burn Care Res 29: 852-855, 2008.
[5] Stavert DM, Archuleta DC, Behr MJ, Lehnert BE: Relative acute toxicities of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in noseand pseudo-mouth-breathing rats. Fund Appl Toxicol 16: 6366-55, 1991.
[11] Forkert PG, Forkert L, Farooqui M, Reynolds ES: Lung injury and repair: DNA synthesis following 1,1-dichloroethylene. Toxicology 36: 199-214, 1985.
[8] Boink AB, Wemer J, Meulenbelt J, Vaessen HA, de Wildt DJ: The mechanism of fluoride-induced hypocalcaemia. Hum Exp Toxicol 13: 149-155, 1994.
References_xml – reference: [1] Tsonis L, Hantsch-Bardsley C, Gamelli RL: Hydrofluoric acid inhalation injury. J Burn Care Res 29: 852-855, 2008.
– reference: [8] Boink AB, Wemer J, Meulenbelt J, Vaessen HA, de Wildt DJ: The mechanism of fluoride-induced hypocalcaemia. Hum Exp Toxicol 13: 149-155, 1994.
– reference: [3] Kawaura F, Fukuoka M, Aragane N, Hayashi S: Acute respiratory distress syndrome induced by hydrogen fluoride gas inhalation. Nihon Kokyuki Gakkai Zasshi 47:991-5, 2009.
– reference: [5] Stavert DM, Archuleta DC, Behr MJ, Lehnert BE: Relative acute toxicities of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in noseand pseudo-mouth-breathing rats. Fund Appl Toxicol 16: 6366-55, 1991.
– reference: [9] Takahashi H, Sano H, Chiba H, Kuroki Y: Plumonary Surfactant Proteins A and D: Innate Immune Functions and Biomarkers for Lung Disease. Curr Pharm Des 12: 589-598, 2006.
– reference: [2] Imanishi M, Dote T, Kono K: Lethal effects on blood and lung during acute respiratory distress after inhalation exposure of rats to aerosolized hydrofluoric acid. Jpn J Occup Med Traumatol 57:109-117, 2009.
– reference: [4] Mitsui G, Dote T, Yamadori E, Adachi K. Kono K : Serum kinetics of fluoride and abnormalities of urinary parameters after single intravenous injection of hydrofluoric acid in rats. Biomed Res Trace Elem 19: 101-104, 2008.
– reference: [10] Beck BD, Gerson B, Feldman HA: Lactate dehydrogenase isoenzymes in hamster lung lavage fluid after lung injury. Toxicol Appl Pharmaco 71: 59-71, 1983.
– reference: [7] Lund K, Refsnes M, Sandstrøm T, Søstrand P, Schwarze P, Boe J, Kongerud J: Increased CD3 positive cells in bronchoalveolar lavage fluid after hydrogen fluoride inhalation. Scand J Work Environ Health 25: 326-334, 1999.
– reference: [6] Pan T, Nielsen L, Allen M, Shannon K, et al: Serum SP-D is a marker of lung injury in rats. American Journal of Physiology - Lung Cell and Molecular Physiology 282: 824-32, 2002.
– reference: [11] Forkert PG, Forkert L, Farooqui M, Reynolds ES: Lung injury and repair: DNA synthesis following 1,1-dichloroethylene. Toxicology 36: 199-214, 1985.
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Snippet Introduction: Hydrofluoric acid (HFA) is commonly used in chemical industries despite reports of acute lethality after occupational accident. We previously...
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SubjectTerms Acute lung injury
Aerosols
Animal models
Blood
Emergency procedures
Fluoride kinetics
Hydrofluoric acid
Inhalation
Inhalation exposure
Light microscopy
Lungs
Occupational safety
Recovery process
Respiratory function
Title Early Recovery Process of Acute Lung Injury and Kinetics of Fluoride in Lung and Blood as the Accidental Model of Inhalation Exposure to Hydrofluoric Acid in Rats
URI https://www.jstage.jst.go.jp/article/brte/23/3/23_202/_article/-char/en
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