ABSTRACT
PURPOSE: To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers (NGALp, NGALu, KIM 1 and IL 18) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury. METHODS: Thirty two Wistar rats were randomly allocated to four groups: Sham (S): laparotomy; Control (C): laparotomy and ischaemia-reperfusion in the left kidney; Control Allopurinol (CA): laparotomy and allopurinol at a dose of 100mg·kg 1·d 1; and Allopurinol (A): laparotomy ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg·kg 1·d 1. The NGALp, NGALu, KIM 1, IL 18 and creatinine levels and the kidney histology were analysed. The significance level was established as p<0.05. RESULTS: Creatinine level increased in all the groups, with A ≈ C > S ≈ CA. The NGALp, NGALu and IL 18 levels exhibited similar behaviour in all the groups. KIM 1 was higher in group A than C and showed intermediate values in groups S and CA. Severity of injury in the left kidney was greater in groups C and A compared to S and CA. CONCLUSION: Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury. .
Subject(s)
Animals , Male , Acute-Phase Proteins/analysis , Allopurinol/pharmacology , Antimetabolites/pharmacology , /analysis , Ischemia/drug therapy , Kidney/blood supply , Kidney/drug effects , Lipocalins/analysis , Proto-Oncogene Proteins/analysis , Acute-Phase Proteins/drug effects , Biomarkers/blood , Creatinine/blood , Kidney/pathology , Lipocalins/drug effects , Proto-Oncogene Proteins/drug effects , Random Allocation , Rats, Wistar , Reperfusion Injury/drug therapy , Reperfusion Injury/pathologyABSTRACT
Lesão renal por isquemia e reperfusão estão envolvidas em muitas condições clínicas. A lesão de reperfusão leva a formação de espécies reativas de oxigênio e o alopurinol apresenta o potencial de diminuí-las. Os novos biomarcadores podem realizar o diagnóstico da lesão de maneira precoce. O objetivo desse estudo foi investigar se o alopurinol tem efeito protetor sobre os rins utilizando os novos biomarcadores de dano (NGALp, NGALu,KIM-1e IL-18), a função renal e a histologia renal durante lesão de isquemia e reperfusão (I/R) em ratos uninefrectomizados. Trinta e dois ratos Wistar foram randomizados em 4 grupos: Sham (S): laparotomia e nefrectomia direita. Controle (C): laparotomia e nefrectomia direita, I/R em rim esquerdo. Controle Alopurinol (CA): laparotomia e nefrectomia direita, alopurinol na dose de 100 mg.kg-1.d-1. Alopurinol (A): laparotomia e nefrectomia direita, I/R em rim esquerdo, alopurinol na dose de 100mg.kg-1.d-1. Foram analisados NGALp, NGALu, IL-18, KIM-1, creatinina e histologia. Nível de significância considerado quando p<0,05. Todos grupos aumentam a creatinina ao longo do experimento com A≈C>S≈CA. A NGALp e IL-18 aumentaram em todos os grupos, porém todos evoluem de forma semelhante. A NGALu aumentou no grupo C, porém todos os grupos evoluem de forma semelhante. KIM-1 foi maior no grupo A em relação ao C e intermediário nos grupos S e CA. Em relação aos achados histológicos, os grupos C e A apresentaram grau de lesão no lado esquerdo significativamente maior que os grupos S e CA. Não existiu diferença histológica entre C e A e nem entre S e CA...
Ischemic and reperfusion kidney injury are involved in many clinical conditions. The reperfusion injury leads to reactive oxygen species formation and allopurinol has the potential to inhibit this process. The novel biomarkers can perform early diagnosis of acute kidney injury. The purpose of this study was to investigate whether allopurinol had a renal protective effect measuring renal function, novel biomarkers levels (pNGAL, uNGAL and IL-18) and studying histopathologic features during renal ischemia-reperfusion (I/R) injury in uninephrectomized rats. 32 Wistar Rats were randomized in 4 groups: Sham (S): laparotomy and right nefrectomy. Control (C): laparotomy and right nefrectomy, I/R maneuvers in left kidney. Allopurinol Control (AC): laparotomy and right nefrectomy, pretreated with allopurinol 100mg.kg-1.d-1. Allopurinol (A): laparotomy and right nefrectomy, I/R maneuvers in left kidney, pretreated with allopurinol 100mg.kg-1.d-1. pNGAL, uNGAL, IL-18, KIM-1, serum creatinine and histopathologic features were analysed. Differences in the mean values were deemed significant at P<0.05. All groups showed a significant rise in serum creatinine throughout the experiment being A≈C>S≈AC. pNGAL and IL-18 showed a significant rise in all groups too, however all of them evolve in a similar way. uNGAL showed signifcantly rise in group C, but all of them evolve in a similar way. KIM-1 was higher in group A than C and had intermediate values in groups S and AC. With regard to histopathologic features, C and A groups showed left kidney injury signifcantly higher than S and AC groups. There were no difference in histopathologic features between groups C and A neither between S and AC...