Metabolism and pulmonary toxicity of intratracheally instilled cupric sulfate in rats

Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping

“…We observed neutrophil influx 24 h postexposure from 60 mg CuO/kg bw both for the pure CuO particle, and the porous silica 300 nm-CuO. This is in the same dose range as previously observed for copper salts, inducing neutrophil influx in the dose range of 6 to 80 mg/kg bw (Hirano et al 1990;Rice et al 2001;Wallenborn et al 2009). A limitation of the current study is that we did not assess the short-term solubility of the studied particles, information that could have been related to their toxic effects.…”

Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping

“…We observed neutrophil influx 24 h postexposure from 60 mg CuO/kg bw both for the pure CuO particle, and the porous silica 300 nm-CuO. This is in the same dose range as previously observed for copper salts, inducing neutrophil influx in the dose range of 6 to 80 mg/kg bw (Hirano et al 1990;Rice et al 2001;Wallenborn et al 2009). A limitation of the current study is that we did not assess the short-term solubility of the studied particles, information that could have been related to their toxic effects.…”

Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats

“…Of these cellular, biochemical and elemental inflammatory indicators, LDH activity and contents of protein, S and Ca were increased linearly with dose up to 20 gg Cu/rat both in CuO-(the present study) and CuSO4-injected (i. t.) rats (Hirano et al 1990b). To compare relative toxicity of Cu compounds in the rat lung, we analyzed a dose-effect relationship of these four inflammatory indicators up to a dose of 20 gg Cu/rat according to the following linear regression formula: Activity or content of an inflammatory indicator = a x {dose of Cu (gg/rat)}+b where a is a slope and b is an intercept.…”

“…The exogenous Cu content of lung tissue was estimated according to an assumption that the endogenous Cu content in the lung tissue was changed proportionally to the lung wet weight during that time period (0.5 h to 1 day after instillation). A half-time of CuO deposited in the rat lung was (Hirano et al 1989a), cadmium chloride (CdC12) -14 days (Hirano et al 1989a), zinc oxide (ZnO) -14 h (Hirano et al 1989 c), yttrium chloride (YC13) -168 days (Hirano et al 1990a) and cupric sulfate (CuSO4) -7.5 h (Hirano et al 1990b). Figure 3 indicates that Cu-binding proteins in the supernatant of lung homogenate were separated into three fractions, which are ceruloplasmin (CP), superoxide dismutase (SOD) and MT fractions, on the gel filtration column.…”

“…To compare the metabolic behavior of CuO (insoluble form of Cu) to that of CuSO4 (soluble form of Cu) in the rat lung, time-course changes in BAL Cu contents following i.t. instillation of CuSO4, which was obtained in the similarly designed study (Hirano et al 1990b), were overlaid on Figs 2A and B (Figs 4A and B). Since CuSO4 (soluble form of Cu) content in the lavageable fluid decreased rapidly, it is reasonable to suppose that the elevated Cu content in the supernatant of BAL fluid of CuO-exposed group from 12 h to 3 days after instillation might be supplied by dissolution of CuO particles.…”

Copper-dependent Inflammation and Nuclear Factor-κ B Activation by Particulate Air Pollution

“…Despite its prominent presence in particulates from the intermountain American west (37), in standardized fine (PM 2.5 ) urban air particles from the National Institute of Standards and Technology (48), and in PM 2.5 samples from multiple sources in the Great Lakes basin (48), copper is currently not regulated as an air pollutant by the Clean Air Act (15). However, copper is toxic for the lung when instilled into the airway (65,66). Brass polishers have an increased smoking-adjusted incidence of chronic bronchitis (67), and women living near copper smelters in the United States suffer increased mortality from acute respiratory diseases (68).…”

Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping

“…We observed neutrophil influx 24 h postexposure from 60 mg CuO/kg bw both for the pure CuO particle, and the porous silica 300 nm-CuO. This is in the same dose range as previously observed for copper salts, inducing neutrophil influx in the dose range of 6 to 80 mg/kg bw (Hirano et al 1990;Rice et al 2001;Wallenborn et al 2009). A limitation of the current study is that we did not assess the short-term solubility of the studied particles, information that could have been related to their toxic effects.…”

Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats

“…Of these cellular, biochemical and elemental inflammatory indicators, LDH activity and contents of protein, S and Ca were increased linearly with dose up to 20 gg Cu/rat both in CuO-(the present study) and CuSO4-injected (i. t.) rats (Hirano et al 1990b). To compare relative toxicity of Cu compounds in the rat lung, we analyzed a dose-effect relationship of these four inflammatory indicators up to a dose of 20 gg Cu/rat according to the following linear regression formula: Activity or content of an inflammatory indicator = a x {dose of Cu (gg/rat)}+b where a is a slope and b is an intercept.…”

“…The exogenous Cu content of lung tissue was estimated according to an assumption that the endogenous Cu content in the lung tissue was changed proportionally to the lung wet weight during that time period (0.5 h to 1 day after instillation). A half-time of CuO deposited in the rat lung was (Hirano et al 1989a), cadmium chloride (CdC12) -14 days (Hirano et al 1989a), zinc oxide (ZnO) -14 h (Hirano et al 1989 c), yttrium chloride (YC13) -168 days (Hirano et al 1990a) and cupric sulfate (CuSO4) -7.5 h (Hirano et al 1990b). Figure 3 indicates that Cu-binding proteins in the supernatant of lung homogenate were separated into three fractions, which are ceruloplasmin (CP), superoxide dismutase (SOD) and MT fractions, on the gel filtration column.…”

“…To compare the metabolic behavior of CuO (insoluble form of Cu) to that of CuSO4 (soluble form of Cu) in the rat lung, time-course changes in BAL Cu contents following i.t. instillation of CuSO4, which was obtained in the similarly designed study (Hirano et al 1990b), were overlaid on Figs 2A and B (Figs 4A and B). Since CuSO4 (soluble form of Cu) content in the lavageable fluid decreased rapidly, it is reasonable to suppose that the elevated Cu content in the supernatant of BAL fluid of CuO-exposed group from 12 h to 3 days after instillation might be supplied by dissolution of CuO particles.…”

Copper-dependent Inflammation and Nuclear Factor-κ B Activation by Particulate Air Pollution

“…Despite its prominent presence in particulates from the intermountain American west (37), in standardized fine (PM 2.5 ) urban air particles from the National Institute of Standards and Technology (48), and in PM 2.5 samples from multiple sources in the Great Lakes basin (48), copper is currently not regulated as an air pollutant by the Clean Air Act (15). However, copper is toxic for the lung when instilled into the airway (65,66). Brass polishers have an increased smoking-adjusted incidence of chronic bronchitis (67), and women living near copper smelters in the United States suffer increased mortality from acute respiratory diseases (68).…”

Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping

“…We observed neutrophil influx 24 h postexposure from 60 mg CuO/kg bw both for the pure CuO particle, and the porous silica 300 nm-CuO. This is in the same dose range as previously observed for copper salts, inducing neutrophil influx in the dose range of 6 to 80 mg/kg bw (Hirano et al 1990;Rice et al 2001;Wallenborn et al 2009). A limitation of the current study is that we did not assess the short-term solubility of the studied particles, information that could have been related to their toxic effects.…”

Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats

“…Of these cellular, biochemical and elemental inflammatory indicators, LDH activity and contents of protein, S and Ca were increased linearly with dose up to 20 gg Cu/rat both in CuO-(the present study) and CuSO4-injected (i. t.) rats (Hirano et al 1990b). To compare relative toxicity of Cu compounds in the rat lung, we analyzed a dose-effect relationship of these four inflammatory indicators up to a dose of 20 gg Cu/rat according to the following linear regression formula: Activity or content of an inflammatory indicator = a x {dose of Cu (gg/rat)}+b where a is a slope and b is an intercept.…”

“…The exogenous Cu content of lung tissue was estimated according to an assumption that the endogenous Cu content in the lung tissue was changed proportionally to the lung wet weight during that time period (0.5 h to 1 day after instillation). A half-time of CuO deposited in the rat lung was (Hirano et al 1989a), cadmium chloride (CdC12) -14 days (Hirano et al 1989a), zinc oxide (ZnO) -14 h (Hirano et al 1989 c), yttrium chloride (YC13) -168 days (Hirano et al 1990a) and cupric sulfate (CuSO4) -7.5 h (Hirano et al 1990b). Figure 3 indicates that Cu-binding proteins in the supernatant of lung homogenate were separated into three fractions, which are ceruloplasmin (CP), superoxide dismutase (SOD) and MT fractions, on the gel filtration column.…”

“…To compare the metabolic behavior of CuO (insoluble form of Cu) to that of CuSO4 (soluble form of Cu) in the rat lung, time-course changes in BAL Cu contents following i.t. instillation of CuSO4, which was obtained in the similarly designed study (Hirano et al 1990b), were overlaid on Figs 2A and B (Figs 4A and B). Since CuSO4 (soluble form of Cu) content in the lavageable fluid decreased rapidly, it is reasonable to suppose that the elevated Cu content in the supernatant of BAL fluid of CuO-exposed group from 12 h to 3 days after instillation might be supplied by dissolution of CuO particles.…”

Copper-dependent Inflammation and Nuclear Factor-κ B Activation by Particulate Air Pollution

“…Despite its prominent presence in particulates from the intermountain American west (37), in standardized fine (PM 2.5 ) urban air particles from the National Institute of Standards and Technology (48), and in PM 2.5 samples from multiple sources in the Great Lakes basin (48), copper is currently not regulated as an air pollutant by the Clean Air Act (15). However, copper is toxic for the lung when instilled into the airway (65,66). Brass polishers have an increased smoking-adjusted incidence of chronic bronchitis (67), and women living near copper smelters in the United States suffer increased mortality from acute respiratory diseases (68).…”