The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min f...The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.展开更多
Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen sp...Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat展开更多
文摘The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.
文摘Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat