AIM： To investigate the effect of Garden/a fasm/noides （GJ） on cerulein-induced acute pancreatitis （AP） in mice. METHODS： C57BL/6 mice weighing 18-20 g were divided into three groups. （1） Normal salinetreated ...AIM： To investigate the effect of Garden/a fasm/noides （GJ） on cerulein-induced acute pancreatitis （AP） in mice. METHODS： C57BL/6 mice weighing 18-20 g were divided into three groups. （1） Normal salinetreated group, （2） treatment with GJ at a dose of 0.1 g/kg, （3） treatment with GJ at a dose of 1 g/kg. GJ was administered orally （n = 6 per group） for 1 wk. Three hours later, the mice were given anintraperitoneal injection of cerulein （50 μg/kg）, a stable cholecystokinin （CCK） analogue, every hour for a total of 6h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70℃ and prepared for the measurement of tissue myeloperoxidase （MPO） activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR （RT-PCR） and real-time PCR measurements. RESULTS： Treatment with G.1 decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with G.1 attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION： These results suggest that GJ attenuated the severity of AP as well as pancreatitisassociated lung injury.展开更多
AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5...AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen(APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH) levels,and malondialdehyde(MDA),reduced glutathione(GSH) and oxidized glutathione(GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels(IU/L) of ALT,AST and LDH were all increased significantly in APAP group(8355 ± 3940 vs 30 ± 21,P < 0.05;6482 ± 4018 vs 146 ± 58,P <0.05;24627 ± 10975 vs 1504 ± 410,P < 0.05).Compared with APAP group,the serum ALT levels(IU/L)(1674 ± 1810 vs 8355 ± 3940,P < 0.05;54 ± 39 vs 8355 ± 3940,P < 0.05;19 ± 9 vs 8355 ± 3940,P < 0.05),AST levels(IU/L)(729 ± 685 vs 6482 ± 4108,P < 0.05;187 ± 149 vs 6482 ± 4108,P < 0.05;141 ± 12 vs 6482 ± 4108,P < 0.05) and LDH levels(IU/L)(7220 ± 6317 vs 24 627 ± 10 975,P < 0.05;1618 ± 719 vs 24 627 ± 10 975,P < 0.05;1394 ± 469 vs 24 627 ± 10 975,P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups.Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP,including hepatocellular necrosis and infiltration of inflammatory cells,and the effect was dose-dependent.MDA levels(nmol/mg) were decreased by 5-MOP in a dose-dependent manner(0.98 ± 0.45 vs 2.15 ± 1.07,P > 0.05;0.59 ± 0.07 vs 2.15 ± 1.07,P < 0.05;0.47 ± 0.06 vs 2.15 ± 1.07,P < 0.05).The pretreatment of 5-MOP could also increase the GSH/GSSG ratio(3.834 ± 0.340 vs 3.306 ± 0.282,P > 0.05;5.330 ± 0.421 vs 3.306 ± 0.282,P < 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P < 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.展开更多
基金The Ministry of Science & Technology (MoST)/Korea Science & Engineering Foundation (KOSEF) through the Vestibulocochlear Research Center (VCRC) at Wonkwang University (R13-2002-055-00000-0)
文摘AIM： To investigate the effect of Garden/a fasm/noides （GJ） on cerulein-induced acute pancreatitis （AP） in mice. METHODS： C57BL/6 mice weighing 18-20 g were divided into three groups. （1） Normal salinetreated group, （2） treatment with GJ at a dose of 0.1 g/kg, （3） treatment with GJ at a dose of 1 g/kg. GJ was administered orally （n = 6 per group） for 1 wk. Three hours later, the mice were given anintraperitoneal injection of cerulein （50 μg/kg）, a stable cholecystokinin （CCK） analogue, every hour for a total of 6h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70℃ and prepared for the measurement of tissue myeloperoxidase （MPO） activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR （RT-PCR） and real-time PCR measurements. RESULTS： Treatment with G.1 decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with G.1 attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION： These results suggest that GJ attenuated the severity of AP as well as pancreatitisassociated lung injury.
基金Supported by Drug Innovation Program of National Science and Technology Project,No.2009ZX09103-007
文摘AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen(APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH) levels,and malondialdehyde(MDA),reduced glutathione(GSH) and oxidized glutathione(GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels(IU/L) of ALT,AST and LDH were all increased significantly in APAP group(8355 ± 3940 vs 30 ± 21,P < 0.05;6482 ± 4018 vs 146 ± 58,P <0.05;24627 ± 10975 vs 1504 ± 410,P < 0.05).Compared with APAP group,the serum ALT levels(IU/L)(1674 ± 1810 vs 8355 ± 3940,P < 0.05;54 ± 39 vs 8355 ± 3940,P < 0.05;19 ± 9 vs 8355 ± 3940,P < 0.05),AST levels(IU/L)(729 ± 685 vs 6482 ± 4108,P < 0.05;187 ± 149 vs 6482 ± 4108,P < 0.05;141 ± 12 vs 6482 ± 4108,P < 0.05) and LDH levels(IU/L)(7220 ± 6317 vs 24 627 ± 10 975,P < 0.05;1618 ± 719 vs 24 627 ± 10 975,P < 0.05;1394 ± 469 vs 24 627 ± 10 975,P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups.Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP,including hepatocellular necrosis and infiltration of inflammatory cells,and the effect was dose-dependent.MDA levels(nmol/mg) were decreased by 5-MOP in a dose-dependent manner(0.98 ± 0.45 vs 2.15 ± 1.07,P > 0.05;0.59 ± 0.07 vs 2.15 ± 1.07,P < 0.05;0.47 ± 0.06 vs 2.15 ± 1.07,P < 0.05).The pretreatment of 5-MOP could also increase the GSH/GSSG ratio(3.834 ± 0.340 vs 3.306 ± 0.282,P > 0.05;5.330 ± 0.421 vs 3.306 ± 0.282,P < 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P < 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.
