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PURPOSE: To evaluate the effects of sirolimus (SRL) on renal injury in rats with bile duct ligation. METHODS: A total of 21 male Sprague-Dawley rats weighing 220-260g were used. Group 1 (Sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n=7) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/SRL, n =7) received a daily dose of sirolimus (0.5 mg·day-1xkg-1 dissolved 1 ml in saline) by orogastric tube for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation were processed. RESULTS: AST, ALT, AP and TB levels values were decreased in group 3 when compared to group 2. There was no significant difference in serum levels of BUN and creatinine among all the experimental groups. Histological evaluation of the liver of BDL/Untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. In BDL/SRL group, moderate damage was seen. Tubular injury scores were higher in the BDL subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. In group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. CONCLUSIONS: Sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. The improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney. OBJETIVO: Investigar os efeitos do sirolimo (SRL) na lesão renal induzida pela ligadura do ducto biliar em ratos. MÉTODOS: Foram utilizados 21 ratos Sprague-Dawley pesando entre 220-260 g. Grupo 1 (Sham-controle, n=7) submetidos a laparotomia e o ducto biliar dissecado do tecido circundante. Grupo 2 (BDL/Não tratado, n=7) foram submetidos a ligadura do ducto biliar e nenhuma droga foi aplicada. Grupo 3 (BDL/SRL, n=7) receberam dose diária de sirolimo (0,5 mg dia-1xkg-1 dissolvido em 1 ml em solução salina) por tubo orogástrico por 14 dias após BDL. Após duas semanas era realizada avaliação bioquímica e histológica. RESULTADOS: Níveis de AST, ALT, AP e TB estavam diminuídos no grupo 3 comparado ao grupo 2. Não houve diferença significante nos níveis séricos de BUN e creatinina em todos os grupos. Observou-se na avaliação histológica evidente fibrose portal e sinais de obstrução do ducto biliar com evidente inflamação portal e lobular. No grupo BDL/SRL verificou-se dano moderado. Lesão tubular foi maior nos subgrupos BDL; entretanto, o grupo 3 mostrou considerável menos lesões nos túbulos e interstício comparados ao grupo 2. No grupo 2 as células epiteliais dos túbulos proximais apresentaram vacúolos e alterações hidrópicas, atrofia e infiltrado celular inflamatório no interstício medular. CONCLUSÕES: Sirolimo diminuiu lesões tubulointersticial no rim induzida pela ligadura do ducto biliar em ratos. Os efeitos benéficos do sirolimo na morfologia renal pode ser devida à melhora da função hepática ou devido à ação direta no rim.

WOS:000282219500004 PubMed: 20877949 Purpose: To evaluate the effects of sirolimus (SRL) on renal injury in rats with bile duct ligation. Methods: A total of 21 male Sprague-Dawley rats weighing 220-260g were used. Group 1 (Sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n=7) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/SRL, n=7) received a daily dose of sirolimus (0.5 mg.day(-1)xkg(-1) dissolved 1 ml in saline) by orogastric tube for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation were processed. Results: AST, ALT, AP and TB levels values were decreased in group 3 when compared to group 2. There was no significant difference in serum levels of BUN and creatinine among all the experimental groups. Histological evaluation of the liver of BDL/Untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. In BDL/SRL group, moderate damage was seen. Tubular injury scores were higher in the BDL subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. In group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. Conclusions: Sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. The improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney.