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Rakesh P. Patel - One of the best experts on this subject based on the ideXlab platform.
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nitrite therapy prevents Chlorine gas toxicity in rabbits
Toxicology Letters, 2017Co-Authors: Jaideep Honavar, Sadis Matalon, Stephen F. Doran, Karina C Ricart, Rakesh P. PatelAbstract:Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury.
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Formation of chlorinated lipids post-Chlorine gas exposure
Journal of lipid research, 2016Co-Authors: David A. Ford, Jaideep Honavar, Sadis Matalon, Carolyn J. Albert, Mark A. Duerr, Stephen F. Doran, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas can occur during accidents and intentional release scenarios. However, biomarkers that specifically indicate Cl2 exposure and Cl2-derived products that mediate postexposure toxicity remain unclear. We hypothesized that chlorinated lipids (Cl-lipids) formed by direct reactions between Cl2 gas and plasmalogens serve as both biomarkers and mediators of post-Cl2 gas exposure toxicities. The 2-chloropalmitaldehyde (2-Cl-Pald), 2-chlorostearaldehyde (2-Cl-Sald), and their oxidized products, free- and esterified 2-chloropalmitic acid (2-Cl-PA) and 2-chlorostearic acid were detected in the lungs and plasma of mouse and rat models of Cl2 gas exposure. Levels of Cl-lipids were highest immediately post-Cl2 gas exposure, and then declined over 72 h with levels remaining 20- to 30-fold higher at 24 h compared with baseline. Glutathione adducts of 2-Cl-Pald and 2-Cl-Sald also increased with levels peaking at 4 h in plasma. Notably, 3-chlorotyrosine also increased after Cl2 gas exposure, but returned to baseline within 24 h. Intranasal administration of 2-Cl-PA or 2-Cl-Pald at doses similar to those formed in the lung after Cl2 gas exposure led to increased distal lung permeability and inflammation and systemic endothelial dysfunction characterized by loss of eNOS-dependent vasodilation. These data suggest that Cl-lipids could serve as biomarkers and mediators for Cl2 gas exposure and toxicity.
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Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature
Toxicology, 2014Co-Authors: Jaideep Honavar, Kelley M Bradley, Sadis Matalon, Stephen F. Doran, Eddie W Bradley, Matthew O Vallejo, Eric E Kelley, Nadiezhda Cantumedellin, Louis J Dellitalia, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ∼2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E(+)) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (∼4mmHg) lower in rats that had been exposed to Cl2 gas 24hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. Language: en
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mitigation of Chlorine gas lung injury in rats by postexposure administration of sodium nitrite
American Journal of Physiology-lung Cellular and Molecular Physiology, 2011Co-Authors: Amit K Yadav, Andrey A Samal, Giuseppe L Squadrito, Edward M Postlethwait, Stephen F. Doran, Ruchita Sharma, Kokilavani Vedagiri, Michelle V Fanucchi, Nd Jackson L Roberts, Rakesh P. PatelAbstract:Nitrite (NO2−) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO2− in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO2− mitigate Chlorine (Cl2)-induced lung injury in rats. Rats were exposed to Cl2 (400 ppm) for 30 min and returned to room air. NO2− (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F2-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO2− resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F2-isoprostane levels increased at 6 and 24 h after Cl2 exposure in NO2−- and saline-injected rats. This is the first demonstration that systemic NO2− administration mitigates airway and epithelial injury.
Sadis Matalon - One of the best experts on this subject based on the ideXlab platform.
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nitrite therapy prevents Chlorine gas toxicity in rabbits
Toxicology Letters, 2017Co-Authors: Jaideep Honavar, Sadis Matalon, Stephen F. Doran, Karina C Ricart, Rakesh P. PatelAbstract:Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury.
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Formation of chlorinated lipids post-Chlorine gas exposure
Journal of lipid research, 2016Co-Authors: David A. Ford, Jaideep Honavar, Sadis Matalon, Carolyn J. Albert, Mark A. Duerr, Stephen F. Doran, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas can occur during accidents and intentional release scenarios. However, biomarkers that specifically indicate Cl2 exposure and Cl2-derived products that mediate postexposure toxicity remain unclear. We hypothesized that chlorinated lipids (Cl-lipids) formed by direct reactions between Cl2 gas and plasmalogens serve as both biomarkers and mediators of post-Cl2 gas exposure toxicities. The 2-chloropalmitaldehyde (2-Cl-Pald), 2-chlorostearaldehyde (2-Cl-Sald), and their oxidized products, free- and esterified 2-chloropalmitic acid (2-Cl-PA) and 2-chlorostearic acid were detected in the lungs and plasma of mouse and rat models of Cl2 gas exposure. Levels of Cl-lipids were highest immediately post-Cl2 gas exposure, and then declined over 72 h with levels remaining 20- to 30-fold higher at 24 h compared with baseline. Glutathione adducts of 2-Cl-Pald and 2-Cl-Sald also increased with levels peaking at 4 h in plasma. Notably, 3-chlorotyrosine also increased after Cl2 gas exposure, but returned to baseline within 24 h. Intranasal administration of 2-Cl-PA or 2-Cl-Pald at doses similar to those formed in the lung after Cl2 gas exposure led to increased distal lung permeability and inflammation and systemic endothelial dysfunction characterized by loss of eNOS-dependent vasodilation. These data suggest that Cl-lipids could serve as biomarkers and mediators for Cl2 gas exposure and toxicity.
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Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature
Toxicology, 2014Co-Authors: Jaideep Honavar, Kelley M Bradley, Sadis Matalon, Stephen F. Doran, Eddie W Bradley, Matthew O Vallejo, Eric E Kelley, Nadiezhda Cantumedellin, Louis J Dellitalia, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ∼2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E(+)) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (∼4mmHg) lower in rats that had been exposed to Cl2 gas 24hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. Language: en
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potential anti inflammatory effects of nebulized local anesthetics on inhaled Chlorine lung injury 834 8
The FASEB Journal, 2014Co-Authors: Buffie Clodfeldermiller, Sadis Matalon, Carey Dewitte, Steve Doran, Timothy J NessAbstract:Chlorine (Cl2) is a chemical used in both industry and society alike, despite it being a highly irritant and reactive gas. Acute exposure can result in symptoms of airway obstruction such as wheezing, shortness of breath, mouth/nose/chest pain, and bronchospasm. Currently, there is no known antidote for Chlorine’s poisoning effects. Potential treatments include topical exposure of the airways to nebulized drugs such as local anesthetics which have been shown to improve the mobility of monitored animals after exposure to Cl2 gas. In this research project, we assess the effects of the nebulized local anesthetics lidocaine (1% and 4%), 3% 2-Chloroprocaine following exposure to 100 or 400 ppm of Chlorine gas on biochemical measurements of injury to airway. Wet-to-dry lung weight ratios, bronchoalveolar lavage (BAL) cell counts and total protein, and lung homogenate cytokine levels were determined 24 hours after Cl2 gas exposure and anesthetic treatment. In mice exposed to 400 ppm Cl2 gas, 1% lidocaine had the...
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inhibition of lung fluid clearance and epithelial na channels by Chlorine hypochlorous acid and chloramines
Journal of Biological Chemistry, 2010Co-Authors: Weifeng Song, Giuseppe L Squadrito, Shipeng Wei, Yongjian Zhou, Ahmed Lazrak, Gang Liu, James D Londino, Sadis MatalonAbstract:We investigated the mechanisms by which Chlorine (Cl2) and its reactive byproducts inhibit Na+-dependent alveolar fluid clearance (AFC) in vivo and the activity of amiloride-sensitive epithelial Na+ channels (ENaC) by measuring AFC in mice exposed to Cl2 (0–500 ppm for 30 min) and Na+ and amiloride-sensitive currents (INa and Iamil, respectively) across Xenopus oocytes expressing human α-, β-, and γ-ENaC incubated with HOCl (1–2000 μm). Both Cl2 and HOCl-derived products decreased AFC in mice and whole cell and single channel INa in a dose-dependent manner; these effects were counteracted by serine proteases. Mass spectrometry analysis of the oocyte recording medium identified organic chloramines formed by the interaction of HOCl with HEPES (used as an extracellular buffer). In addition, chloramines formed by the interaction of HOCl with taurine or glycine decreased INa in a similar fashion. Preincubation of oocytes with serine proteases prevented the decrease of INa by HOCl, whereas perfusion of oocytes with a synthetic 51-mer peptide corresponding to the putative furin and plasmin cleaving segment in the γ-ENaC subunit restored the ability of HOCl to inhibit INa. Finally, INa of oocytes expressing wild type α- and γ-ENaC and a mutant form of βENaC (S520K), known to result in ENaC channels locked in the open position, were not altered by HOCl. We concluded that HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage.
Tadatsugu Minami - One of the best experts on this subject based on the ideXlab platform.
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high sensitivity Chlorine gas sensors using multicomponent transparent conducting oxide thin films
Sensors and Actuators B-chemical, 2000Co-Authors: Toshihiro Miyata, Tomohiro Hikosaka, Tadatsugu MinamiAbstract:Abstract Newly developed semiconductor thin-film gas sensors with a high sensitivity for Chlorine (Cl2) gas using multicomponent transparent conducting oxide (TCO) thin films such as MgO–In2O3, ZnO–In2O3 and Zn2In2O5–MgIn2O4 are described. The multicomponent oxide thin-film gas sensors used in this work exhibited an increase in resistance with exposure to Cl2 gas. The sensitivity of multicomponent TCO thin-film gas sensors could be controlled by altering the chemical composition of the thin-films. The highest sensitivity for Cl2 gas was obtained in sensors using a Zn2In2O5–MgIn2O4 thin film prepared with Zn2In2O5 contents of about 60 mol%; when operated at 300°C in air, they were able to detect Cl2 gas at a minimum concentration of 0.01 ppm. The sensitivity or resistance of these (Zn2In2O5)0.6–(MgIn2O4)0.4 thin-film gas sensors was increased by a factor of about 100 when exposed to Cl2 gas with a concentration of 7 ppm. An increase of resistivity in multicomponent TCO thin-film sensors with exposure to Cl2 gas resulted from a simultaneous decrease of both carrier concentration and Hall mobility. The increase in resistivity is attributed to the trapping of free electrons resulting from Cl2 being adsorbed on grain boundaries and/or the thin film surface, the same as that produced by adsorption of oxygen. The sensitivity and resistance of Zn2In2O5–MgIn2O4 thin-film gas sensors exhibited very stable long-term operation in air containing a high concentration of Cl2 gas.
Toshihiro Miyata - One of the best experts on this subject based on the ideXlab platform.
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high sensitivity Chlorine gas sensors using cu phthalocyanine thin films
Thin Solid Films, 2003Co-Authors: Toshihiro Miyata, Seiji Kawaguchi, Makoto Ishii, Tadastugu MinamiAbstract:Abstract High sensitivity Chlorine (Cl2) gas detection has been realized by newly developed gas sensors using Cu–phthalocyanine (CuPc) thin films. The CuPc thin film gas sensors exhibited an increase of conductivity with exposure to Cl2 gas. The sensing properties of the CuPc thin film gas sensors were strongly dependent on the preparation conditions of CuPc thin films. The highest sensitivity for Cl2 gas was obtained in the gas sensor using CuPc thin film prepared under the optimized preparation conditions: substrate temperature of 170 °C, evaporation temperature of 475 °C and film thickness of 50 nm. It was found that Cl2 gas detection was realized at a minimum concentration of 0.18 ppm.
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high sensitivity Chlorine gas sensors using multicomponent transparent conducting oxide thin films
Sensors and Actuators B-chemical, 2000Co-Authors: Toshihiro Miyata, Tomohiro Hikosaka, Tadatsugu MinamiAbstract:Abstract Newly developed semiconductor thin-film gas sensors with a high sensitivity for Chlorine (Cl2) gas using multicomponent transparent conducting oxide (TCO) thin films such as MgO–In2O3, ZnO–In2O3 and Zn2In2O5–MgIn2O4 are described. The multicomponent oxide thin-film gas sensors used in this work exhibited an increase in resistance with exposure to Cl2 gas. The sensitivity of multicomponent TCO thin-film gas sensors could be controlled by altering the chemical composition of the thin-films. The highest sensitivity for Cl2 gas was obtained in sensors using a Zn2In2O5–MgIn2O4 thin film prepared with Zn2In2O5 contents of about 60 mol%; when operated at 300°C in air, they were able to detect Cl2 gas at a minimum concentration of 0.01 ppm. The sensitivity or resistance of these (Zn2In2O5)0.6–(MgIn2O4)0.4 thin-film gas sensors was increased by a factor of about 100 when exposed to Cl2 gas with a concentration of 7 ppm. An increase of resistivity in multicomponent TCO thin-film sensors with exposure to Cl2 gas resulted from a simultaneous decrease of both carrier concentration and Hall mobility. The increase in resistivity is attributed to the trapping of free electrons resulting from Cl2 being adsorbed on grain boundaries and/or the thin film surface, the same as that produced by adsorption of oxygen. The sensitivity and resistance of Zn2In2O5–MgIn2O4 thin-film gas sensors exhibited very stable long-term operation in air containing a high concentration of Cl2 gas.
Stephen F. Doran - One of the best experts on this subject based on the ideXlab platform.
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nitrite therapy prevents Chlorine gas toxicity in rabbits
Toxicology Letters, 2017Co-Authors: Jaideep Honavar, Sadis Matalon, Stephen F. Doran, Karina C Ricart, Rakesh P. PatelAbstract:Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury.
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Formation of chlorinated lipids post-Chlorine gas exposure
Journal of lipid research, 2016Co-Authors: David A. Ford, Jaideep Honavar, Sadis Matalon, Carolyn J. Albert, Mark A. Duerr, Stephen F. Doran, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas can occur during accidents and intentional release scenarios. However, biomarkers that specifically indicate Cl2 exposure and Cl2-derived products that mediate postexposure toxicity remain unclear. We hypothesized that chlorinated lipids (Cl-lipids) formed by direct reactions between Cl2 gas and plasmalogens serve as both biomarkers and mediators of post-Cl2 gas exposure toxicities. The 2-chloropalmitaldehyde (2-Cl-Pald), 2-chlorostearaldehyde (2-Cl-Sald), and their oxidized products, free- and esterified 2-chloropalmitic acid (2-Cl-PA) and 2-chlorostearic acid were detected in the lungs and plasma of mouse and rat models of Cl2 gas exposure. Levels of Cl-lipids were highest immediately post-Cl2 gas exposure, and then declined over 72 h with levels remaining 20- to 30-fold higher at 24 h compared with baseline. Glutathione adducts of 2-Cl-Pald and 2-Cl-Sald also increased with levels peaking at 4 h in plasma. Notably, 3-chlorotyrosine also increased after Cl2 gas exposure, but returned to baseline within 24 h. Intranasal administration of 2-Cl-PA or 2-Cl-Pald at doses similar to those formed in the lung after Cl2 gas exposure led to increased distal lung permeability and inflammation and systemic endothelial dysfunction characterized by loss of eNOS-dependent vasodilation. These data suggest that Cl-lipids could serve as biomarkers and mediators for Cl2 gas exposure and toxicity.
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Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature
Toxicology, 2014Co-Authors: Jaideep Honavar, Kelley M Bradley, Sadis Matalon, Stephen F. Doran, Eddie W Bradley, Matthew O Vallejo, Eric E Kelley, Nadiezhda Cantumedellin, Louis J Dellitalia, Rakesh P. PatelAbstract:Exposure to Chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ∼2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E(+)) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (∼4mmHg) lower in rats that had been exposed to Cl2 gas 24hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. Language: en
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mitigation of Chlorine gas lung injury in rats by postexposure administration of sodium nitrite
American Journal of Physiology-lung Cellular and Molecular Physiology, 2011Co-Authors: Amit K Yadav, Andrey A Samal, Giuseppe L Squadrito, Edward M Postlethwait, Stephen F. Doran, Ruchita Sharma, Kokilavani Vedagiri, Michelle V Fanucchi, Nd Jackson L Roberts, Rakesh P. PatelAbstract:Nitrite (NO2−) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO2− in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO2− mitigate Chlorine (Cl2)-induced lung injury in rats. Rats were exposed to Cl2 (400 ppm) for 30 min and returned to room air. NO2− (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F2-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO2− resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F2-isoprostane levels increased at 6 and 24 h after Cl2 exposure in NO2−- and saline-injected rats. This is the first demonstration that systemic NO2− administration mitigates airway and epithelial injury.
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mitigation of Chlorine induced lung injury by low molecular weight antioxidants
American Journal of Physiology-lung Cellular and Molecular Physiology, 2008Co-Authors: Martin Leustik, Giuseppe L Squadrito, Edward M Postlethwait, Stephen F. Doran, Andreas Bracher, Shawn Williams, Trenton R Schoeb, Sadis MatalonAbstract:Chlorine (Cl2) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of Cl2 results in acute lung injury that may either resolve spo...