Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury.
Braz J Med Biol Res
; 43(8): 737-44, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20549136
ABSTRACT
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 nanog/mL); CsA (100 microg/mL); sirolimus (50 and 250 nanog/mL) + CsA (100 microg/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 x kg(-1) x day(-1), po), I + CsA (3 mg x kg(-1) x 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Ciclosporina
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Sirolimo
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Imunossupressores
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Rim
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Túbulos Renais Proximais
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article