Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats
ABSTRACT Objective: to evaluate the renal toxicity caused by tacrolimus and mycophenolate mofetil (MMF) in a single kidney ischemia and reperfusion model. Method: experimental study using Wistar rats, submitted to right nephrectomy and left renal ischemia for 20 minutes, separated into groups in...
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Colégio Brasileiro de Cirurgiões
2022-08-01
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| Series: | Revista do Colégio Brasileiro de Cirurgiões |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-69912022000100224&tlng=pt |
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| author | ALEXANDRE CAVALHEIRO CAVALLI LUIS FERNANDO MACENTE SALA JULIO SLONGO ROGERIO DE FRAGA RENATO TAMBARA FILHO |
| author_facet | ALEXANDRE CAVALHEIRO CAVALLI LUIS FERNANDO MACENTE SALA JULIO SLONGO ROGERIO DE FRAGA RENATO TAMBARA FILHO |
| author_sort | ALEXANDRE CAVALHEIRO CAVALLI |
| collection | DOAJ |
| description | ABSTRACT Objective: to evaluate the renal toxicity caused by tacrolimus and mycophenolate mofetil (MMF) in a single kidney ischemia and reperfusion model. Method: experimental study using Wistar rats, submitted to right nephrectomy and left renal ischemia for 20 minutes, separated into groups in the postoperative period (PO): 1) Control (nonoperated); 2) Sham (operated, without PO drug); 3) TAC0.1, TAC1 and TAC10, tacrolimus administered PO at doses of 0.1mg/kg, 1mg/kg and 10mg/kg via gavage, respectively; 4) MMF, administered mycophenolate mofetil 20mg/kg; 5) MMF/TAC1 and MMF/TAC0.5, with an association of mycophenolate mofetil 20mg/kg and tacrolimus 1mg/kg and 0.5mg/kg, respectively. They were killed on the 14th PO and the kidney was removed for tissue oxidative stress analysis, by the dosage of reduced glutathione (GSH), lipoperoxidation (LPO) and protein carbonylation (PCO), and histological analysis by glomerular stereology (Glomerular volume density, Numerical density glomerular and mean glomerular volume). Renal function was evaluated by the measurement of serum creatinine and urea. Results: both drugs caused alterations in renal function, and the toxicity of tacrolimus was dose-dependent. Subacute toxicity did not show significant glomerular histological changes, and there was renal and compensatory glomerular hypertrophy in all groups except TAC10. Conclusion: Both drugs cause changes in renal function. Glomerular morphometry and stereology showed negative interference of immunosuppressants during compensatory glomerular hypertrophy. |
| first_indexed | 2024-04-13T19:02:48Z |
| format | Article |
| id | doaj.art-b7ffb0a592f14082bbf2d7ce3d13cede |
| institution | Directory Open Access Journal |
| issn | 1809-4546 |
| language | English |
| last_indexed | 2024-04-13T19:02:48Z |
| publishDate | 2022-08-01 |
| publisher | Colégio Brasileiro de Cirurgiões |
| record_format | Article |
| series | Revista do Colégio Brasileiro de Cirurgiões |
| spelling | doaj.art-b7ffb0a592f14082bbf2d7ce3d13cede2022-12-22T02:34:03ZengColégio Brasileiro de CirurgiõesRevista do Colégio Brasileiro de Cirurgiões1809-45462022-08-014910.1590/0100-6991e-20223233-enEvaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in ratsALEXANDRE CAVALHEIRO CAVALLILUIS FERNANDO MACENTE SALAhttps://orcid.org/0000-0003-1464-2437JULIO SLONGOhttps://orcid.org/0000-0001-9895-6972ROGERIO DE FRAGAhttps://orcid.org/0000-0002-9012-3922RENATO TAMBARA FILHOhttps://orcid.org/0000-0001-7603-8134ABSTRACT Objective: to evaluate the renal toxicity caused by tacrolimus and mycophenolate mofetil (MMF) in a single kidney ischemia and reperfusion model. Method: experimental study using Wistar rats, submitted to right nephrectomy and left renal ischemia for 20 minutes, separated into groups in the postoperative period (PO): 1) Control (nonoperated); 2) Sham (operated, without PO drug); 3) TAC0.1, TAC1 and TAC10, tacrolimus administered PO at doses of 0.1mg/kg, 1mg/kg and 10mg/kg via gavage, respectively; 4) MMF, administered mycophenolate mofetil 20mg/kg; 5) MMF/TAC1 and MMF/TAC0.5, with an association of mycophenolate mofetil 20mg/kg and tacrolimus 1mg/kg and 0.5mg/kg, respectively. They were killed on the 14th PO and the kidney was removed for tissue oxidative stress analysis, by the dosage of reduced glutathione (GSH), lipoperoxidation (LPO) and protein carbonylation (PCO), and histological analysis by glomerular stereology (Glomerular volume density, Numerical density glomerular and mean glomerular volume). Renal function was evaluated by the measurement of serum creatinine and urea. Results: both drugs caused alterations in renal function, and the toxicity of tacrolimus was dose-dependent. Subacute toxicity did not show significant glomerular histological changes, and there was renal and compensatory glomerular hypertrophy in all groups except TAC10. Conclusion: Both drugs cause changes in renal function. Glomerular morphometry and stereology showed negative interference of immunosuppressants during compensatory glomerular hypertrophy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-69912022000100224&tlng=ptTacrolimusOxidative StressImmunologyReperfusion |
| spellingShingle | ALEXANDRE CAVALHEIRO CAVALLI LUIS FERNANDO MACENTE SALA JULIO SLONGO ROGERIO DE FRAGA RENATO TAMBARA FILHO Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats Revista do Colégio Brasileiro de Cirurgiões Tacrolimus Oxidative Stress Immunology Reperfusion |
| title | Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats |
| title_full | Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats |
| title_fullStr | Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats |
| title_full_unstemmed | Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats |
| title_short | Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats |
| title_sort | evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion experimental study in rats |
| topic | Tacrolimus Oxidative Stress Immunology Reperfusion |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-69912022000100224&tlng=pt |
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