Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacolog...Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.展开更多
Although 9.4 T magnetic resonance imaging(MRI) has been tested in healthy volunteers,its safety in diabetic patients is unclear.Furthermore,the effects of high static magnetic fields(SMFs),especially gradient vs.unifo...Although 9.4 T magnetic resonance imaging(MRI) has been tested in healthy volunteers,its safety in diabetic patients is unclear.Furthermore,the effects of high static magnetic fields(SMFs),especially gradient vs.uniform fields,have not been investigated in diabetics.Here,we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients(>10 T/m vs.0-10 T/m)on type 1 diabetic(T1D) and type 2 diabetic(T2D) mice.We found that 14 h of prolonged treatment of gradient(as high as 55.5 T/m) high SMFs(1.0-8.6 T) had negative effects on T1D and T2D mice,including spleen,hepatic,and renal tissue impairment and elevated glycosylated serum protein,blood glucose,inflammation,and anxiety,while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects.In regular T1D mice(blood glucose>16.7 mmol/L),the>10 T/m gradient high SMFs increased malondialdehyde(P<0.01) and decreased superoxide dismutase(P<0.05).However,in the severe T1D mice(blood glucose≥30.0 mmol/L),the>10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate.In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation.Therefore,this study showed that prolonged exposure to high-field(1.0-8.6 T)>10 T/m gradient SMFs(35-1 380 times higher than that of current clinical MRI)can have negative effects on diabetic mice,especially mice with severe T1D,whereas 9.4 T high SMFs at 0-10T/m did not produce the same effects,providing important information for the future development and clinical application of SMFs,especially high-field MRI.展开更多
基金supported by the National Key R&D Program of China(2023YFB3507004)National Natural Science Foundation of China(U21A20148)+5 种基金International Partnership Program of Chinese Academy of Sciences(116134KYSB20210052)Anhui Provincial Natural Science Foundation(2308085QE183,2308085QE181)CASHIPS Director’s Fund(YZJJ2024QN44,YZJJ2023QN43)Heye Health Technology Chong Ming Project(HYCMP2021010)China Post-doctoral Science Foundation(2023M743536)Science Research Fund for Postdoctoral in Anhui Province(2023B669)。
文摘Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.
基金supported by the National Natural Science Foundation of China (U21A20148, 31900506, 52007185)International Partnership Program of the Chinese Academy of Sciences(116134KYSB20210052)+2 种基金Heye Health Technology Chong Ming Project(HYCMP2021010)CAS President’s International Fellowship Initiative Grant(2022VMA0009)CASHIPS Director’s Fund (BJPY2021A06,2021YZGH04, YZJJ2020QN26, YZJJZX202014, YZJJ2021QN32,YZJJ2023QN43)。
文摘Although 9.4 T magnetic resonance imaging(MRI) has been tested in healthy volunteers,its safety in diabetic patients is unclear.Furthermore,the effects of high static magnetic fields(SMFs),especially gradient vs.uniform fields,have not been investigated in diabetics.Here,we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients(>10 T/m vs.0-10 T/m)on type 1 diabetic(T1D) and type 2 diabetic(T2D) mice.We found that 14 h of prolonged treatment of gradient(as high as 55.5 T/m) high SMFs(1.0-8.6 T) had negative effects on T1D and T2D mice,including spleen,hepatic,and renal tissue impairment and elevated glycosylated serum protein,blood glucose,inflammation,and anxiety,while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects.In regular T1D mice(blood glucose>16.7 mmol/L),the>10 T/m gradient high SMFs increased malondialdehyde(P<0.01) and decreased superoxide dismutase(P<0.05).However,in the severe T1D mice(blood glucose≥30.0 mmol/L),the>10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate.In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation.Therefore,this study showed that prolonged exposure to high-field(1.0-8.6 T)>10 T/m gradient SMFs(35-1 380 times higher than that of current clinical MRI)can have negative effects on diabetic mice,especially mice with severe T1D,whereas 9.4 T high SMFs at 0-10T/m did not produce the same effects,providing important information for the future development and clinical application of SMFs,especially high-field MRI.
