Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury
Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygen...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2010-08-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000800007 |
| _version_ | 1811299719500005376 |
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| author | B.J. Pereira I. Castro E.A. Burdmann D.M.A. Malheiros L. Yu |
| author_facet | B.J. Pereira I. Castro E.A. Burdmann D.M.A. Malheiros L. Yu |
| author_sort | B.J. Pereira |
| collection | DOAJ |
| description | Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL); CsA (100 µg/mL); sirolimus (50 and 250 ηg/mL) + CsA (100 µg/mL); control; vehicle (20% ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity. |
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| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-04-13T06:40:56Z |
| publishDate | 2010-08-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-2a0c6bcab6ad431384983cf615bf2dad2022-12-22T02:57:45ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2010-08-01438737744Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injuryB.J. PereiraI. CastroE.A. BurdmannD.M.A. MalheirosL. YuCalcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL); CsA (100 µg/mL); sirolimus (50 and 250 ηg/mL) + CsA (100 µg/mL); control; vehicle (20% ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000800007Cyclosporin ANephrotoxicityRenal proximal tubulesRenal ischemia |
| spellingShingle | B.J. Pereira I. Castro E.A. Burdmann D.M.A. Malheiros L. Yu Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury Brazilian Journal of Medical and Biological Research Cyclosporin A Nephrotoxicity Renal proximal tubules Renal ischemia |
| title | Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury |
| title_full | Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury |
| title_fullStr | Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury |
| title_full_unstemmed | Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury |
| title_short | Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury |
| title_sort | effects of sirolimus alone or in combination with cyclosporine a on renal ischemia reperfusion injury |
| topic | Cyclosporin A Nephrotoxicity Renal proximal tubules Renal ischemia |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000800007 |
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