>
Fa   |   Ar   |   En
   Cyclosporine a-induced nephrotoxicity is ameliorated by dose reduction and conversion to sirolimus in the rat  
   
نویسنده sereno j. ,vala h. ,nunes s. ,rocha-pereira p. ,carvalho e. ,alves r. ,teixeira f. ,reis f.
منبع journal of physiology and pharmacology - 2015 - دوره : 66 - شماره : 2 - صفحه:285 -299
چکیده    Side-effect minimization strategies to avoid serious side-effects of cyclosporine a (csa),such as nephrotoxicity,have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs,such as sirolimus (srl),an inhibitor of the mammalian target of rapamycin. this study intended to evaluate the impact of protocols based on csa dose reduction and further conversion to srl on kidney function and lesions,based on serum,urine and renal tissue markers. the following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); csa (5 mg/kg/day) and red + conv (csa 30 mg/kg/day during 3 weeks + 3 weeks with csa 5 mg/kg/day + srl 1 mg/kg/day during the last 3 weeks). the following parameters were analysed: blood pressure,heart rate and biochemical data; serum and urine contents and clearances of creatinine,urea and neutrophil gelatinase-associated lipocalin (ngal),as well as,glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. after the first 3 weeks of csa (30 mg/kg/day) treatment animals showed body weight loss,hypertension,tachycardia,as well as,increased serum levels of non-hdl cholesterol,glucose,triglycerides,creatinine and urea,accompanied by decreased gfr and insulin levels. in addition,a significant increase in the expression of connective tissue growth factor,kidney injury molecule-1 (kim-1),mammalian target of rapamycin,nuclear factor-κβ1 and transforming growth factor-β was found in the kidney,accompanied by extensive renal damage. the following 3 weeks with csa dose reduction revealed amelioration of vascular and glomerular lesions,but without significant tubular improvement. the last 3 weeks with the conversion to sirolimus revealed high serum and urine ngal contents but the csa-evoked renal damage was substantially ameliorated,by reduced of connective tissue growth factor,mammalian target of rapamycin,nuclear factor-κβ1 protein expression. in conclusion,csa nephrotoxicity is dose dependent and moderate dysfunction could be ameliorated/prevented by srl conversion,which could be pivotal for the preservation of kidney function and structure. © 2015,polish physiological society. all rights reserved.
کلیدواژه Connective tissue growth factor; Cyclosporine; Nephrotoxicity; Neutrophil gelatinase-associated lipocalin; Reduction plus conversion protocol; Renal lesion; Serum; Sirolimus; Urine and renal tissue biomarkers
آدرس laboratory of pharmacology and experimental therapeutics,institute for biomedical imaging and life sciences,university of coimbra,coimbra,portugal,center for neuroscience and cell biology,institute for biomedical imaging and life sciences (cnc.ibili),university of coimbra,coimbra,portugal,institute for nuclear sciences applied to health,university of coimbra,coimbra, Portugal, center for studies in education and health technologies,ci and dets agrarian school of viseu,polytechnic institute of viseu,viseu, Portugal, laboratory of pharmacology and experimental therapeutics,institute for biomedical imaging and life sciences,university of coimbra,coimbra,portugal,center for neuroscience and cell biology,institute for biomedical imaging and life sciences (cnc.ibili),university of coimbra,coimbra, Portugal, research centre for health sciences,beira interior university,covilha, Portugal, center for neuroscience and cell biology,institute for biomedical imaging and life sciences (cnc.ibili),university of coimbra,coimbra,portugal,the portuguese diabetes association (apdp),lisbon, Portugal, university nephrology unit,university of coimbra,coimbra, Portugal, laboratory of pharmacology and experimental therapeutics,institute for biomedical imaging and life sciences,university of coimbra,coimbra,portugal,center for neuroscience and cell biology,institute for biomedical imaging and life sciences (cnc.ibili),university of coimbra,coimbra, Portugal, laboratory of pharmacology and experimental therapeutics,institute for biomedical imaging and life sciences,university of coimbra,coimbra,portugal,center for neuroscience and cell biology,institute for biomedical imaging and life sciences (cnc.ibili),university of coimbra,coimbra, Portugal
 
     
   
Authors
  
 
 

Copyright 2023
Islamic World Science Citation Center
All Rights Reserved