Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease

Objective: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss of renal function and cyst progression compared to rapamycin in Han: SPRD rats. We also sought to assess whether the effect of combination therapy of MMF plus rapamycin was better than that of monotherapy. Methods: Sixt...

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Autores principales:	ZHANG,TONG, WANG,LI, XIONG,XISHAN, MAO,ZHIGUO, WANG,LIMING, MEI,CHANGLIN
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2009
Materias:	ADPKD Han: SPRD rat mycophenolate mofetil rapamycin
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400005
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spelling	oai:scielo:S0716-976020090004000052010-03-17Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney DiseaseZHANG,TONGWANG,LIXIONG,XISHANMAO,ZHIGUOWANG,LIMINGMEI,CHANGLIN ADPKD Han: SPRD rat mycophenolate mofetil rapamycin Objective: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss of renal function and cyst progression compared to rapamycin in Han: SPRD rats. We also sought to assess whether the effect of combination therapy of MMF plus rapamycin was better than that of monotherapy. Methods: Sixty heterozygous (Cy/+) and littermate control (+/+) male Han: SPRD rats were weaned at 4 weeks of age, then divided into four groups randomly to receive different treatments by intragastric administration for 2 months: vehicle-treated group as control, MMF-treated group (20mg/kg/day), rapamycin-treated group (2mg/kg/day), and MMF+Rapa- treated group (MMF 20mg/kg/day plus Rapamycin 2mg/kg/day). Resulls: After 2 months of treatment, rapamycin caused a 22 % decrease in body weight in comparison to the control group, whereas MMF had no significant effect on weight gain. The steady increase of BUN in Cy/+ rats was reduced by 15% in MMF-treated Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42% and 43%, respectively. CCr was 0.93±0.11ml/min in vehicle-treated Cy/+ rats, 1.67±0.23 ml/min in MMF-treated Cy/+ rats (P<0.05), 1.72±0.44 ml/min and 1.83±0.21 ml/min in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (.P<0.01). Cyst volume density was 57.1 % in vehicle-treated Cy/+ rats, 45.2% in MMF-treated Cy/+ rats (P<0.05), 32.9% and 37.7% in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (P<0.01). MMF markedly ameliorated interstitial inflammation and fibrosis. Rapamycin showed a similar effect on interstitial inflammation and fibrosis, but to a lesser degree. Conclusion : MMF is more tolerable than rapamycin and can retard deterioration of renal function in Han: SPRD rats, though its effect is weaker than that of rapamycin. Combination therapy does not exert more favorable effect than monotherapy.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.42 n.4 20092009-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400005en10.4067/S0716-97602009000400005
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	ADPKD Han: SPRD rat mycophenolate mofetil rapamycin
spellingShingle	ADPKD Han: SPRD rat mycophenolate mofetil rapamycin ZHANG,TONG WANG,LI XIONG,XISHAN MAO,ZHIGUO WANG,LIMING MEI,CHANGLIN Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
description	Objective: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss of renal function and cyst progression compared to rapamycin in Han: SPRD rats. We also sought to assess whether the effect of combination therapy of MMF plus rapamycin was better than that of monotherapy. Methods: Sixty heterozygous (Cy/+) and littermate control (+/+) male Han: SPRD rats were weaned at 4 weeks of age, then divided into four groups randomly to receive different treatments by intragastric administration for 2 months: vehicle-treated group as control, MMF-treated group (20mg/kg/day), rapamycin-treated group (2mg/kg/day), and MMF+Rapa- treated group (MMF 20mg/kg/day plus Rapamycin 2mg/kg/day). Resulls: After 2 months of treatment, rapamycin caused a 22 % decrease in body weight in comparison to the control group, whereas MMF had no significant effect on weight gain. The steady increase of BUN in Cy/+ rats was reduced by 15% in MMF-treated Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42% and 43%, respectively. CCr was 0.93±0.11ml/min in vehicle-treated Cy/+ rats, 1.67±0.23 ml/min in MMF-treated Cy/+ rats (P<0.05), 1.72±0.44 ml/min and 1.83±0.21 ml/min in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (.P<0.01). Cyst volume density was 57.1 % in vehicle-treated Cy/+ rats, 45.2% in MMF-treated Cy/+ rats (P<0.05), 32.9% and 37.7% in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (P<0.01). MMF markedly ameliorated interstitial inflammation and fibrosis. Rapamycin showed a similar effect on interstitial inflammation and fibrosis, but to a lesser degree. Conclusion : MMF is more tolerable than rapamycin and can retard deterioration of renal function in Han: SPRD rats, though its effect is weaker than that of rapamycin. Combination therapy does not exert more favorable effect than monotherapy.
author	ZHANG,TONG WANG,LI XIONG,XISHAN MAO,ZHIGUO WANG,LIMING MEI,CHANGLIN
author_facet	ZHANG,TONG WANG,LI XIONG,XISHAN MAO,ZHIGUO WANG,LIMING MEI,CHANGLIN
author_sort	ZHANG,TONG
title	Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
title_short	Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
title_full	Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
title_fullStr	Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
title_full_unstemmed	Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease
title_sort	mycophenolate mofetil versus rapamycin in han: sprd rats with polycystic kidney disease
publisher	Sociedad de Biología de Chile
publishDate	2009
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400005
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Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease

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