典型文献
Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice
文献摘要：
Treatment with aprotinin,a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da,was associated with acute kidney injury,which was one of the reasons for withdrawal from the market in 2007.Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism.Herein,we studied the effect of aprotinin in wild-type 129S1/SvlmJ mice on sodium handling,tubular function,and integrity under a control and low-salt diet.Mice were studied in metabolic cages,and aprotinin was delivered by subcutaneously implanted sustained release pellets(2 mg/day over 10 days).Mean urinary aprotinin concentration ranged between 642±135(day 2)and 127±16(day 8)μg/mL.Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly,proteolytic activation of ENaC.Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria.Plasma urea and cystatin C concentration increased significantly under aprotinin treatment.Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1(KIM-1).In electron microscopy,electron-dense deposits were observed.There was no evidence for kidney injury in mice treated with a lower aprotinin dose(0.5 mg/day).In conclusion,high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice,leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.
文献关键词：
中图分类号：
作者姓名：
Stefan W?rnier;Bernhard N.Bohnert;Matthias W?rn;Mengyun Xiao;Andrea Janessa;Andreas L.Birkenfeld;Kerstin Amann;Christoph Daniel;Ferruh Artunc
作者机构：
Division of Endocrinology,Diabetology and Nephrology,Department of Internal Medicine,University Hospital Tubingen,Tubingen,Germany;Institute of Diabetes Research and Metabolic Diseases(IDM)of the Helmholtz Center Munich at the University Tubingen,Tubingen,Germany;German Center for Diabetes Research(DZD)at the University Tubingen,Tubingen,Germany;Department of Nephropathology,Friedrich-Alexander University(FAU)Erlangen-Nurnberg(FAU),Erlangen,Germany
文献出处：
引用格式：
[1]Stefan W?rnier;Bernhard N.Bohnert;Matthias W?rn;Mengyun Xiao;Andrea Janessa;Andreas L.Birkenfeld;Kerstin Amann;Christoph Daniel;Ferruh Artunc-.Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice)[J].中国药理学报（英文版）,2022(01):111-120
A类：
aprotinin,129S1,SvlmJ,Aprotinin,glucosuria,nephrotoxic,counterregulatory
B类：
Renal,effects,serine,inhibitor,healthy,conscious,mice,Treatment,broad,spectrum,molecular,weight,Da,was,associated,acute,kidney,injury,which,one,reasons,withdrawal,from,market,Inhibition,renal,proteases,regulating,epithelial,sodium,channel,ENaC,could,possible,mechanism,Herein,studied,wild,type,handling,tubular,function,integrity,under,control,salt,diet,Mice,were,metabolic,cages,delivered,by,subcutaneously,implanted,sustained,release,pellets,over,days,Mean,urinary,concentration,ranged,between,caused,impaired,preservation,while,stimulating,excessive,hyperaldosteronism,unexpectedly,proteolytic,activation,inhibited,proximal,leading,proteinuria,Plasma,urea,cystatin,increased,significantly,treatment,Kidney,tissues,treated,showed,accumulation,intracellular,expression,molecule,KIM,electron,microscopy,dense,deposits,observed,There,no,evidence,lower,conclusion,high,doses,exert,system,inhibition,stimulation,mediated,transport
AB值：
0.522232
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