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ABSTRACT Introduction: Renal ischemia (I) could develop due to decreased or ceased blood flow to the kidney in some clinical conditions such as shock, sepsis, and kidney transplantation. The re-supply of blood to the kidney is called reperfusion (R). Ischemia and reperfusion periods can cause severe kidney damage. Objectives: When we examined the I/R molecular progression, antioxidant molecules such as vitamin A seem promising treatment agents. This study aimed to investigate the effects of vitamin A on renal I/R injury. Material and Methods: In the study, 40 Sprague-Dawley male rats were divided into five groups (n=8): the control group, only I/R, I/R+1000, I/R+3000, and I/R+9000 IU/kg of Vitamin A groups. Vitamin A was administrated to each group for seven days via oral gavage. Blood and kidney tissue samples were collected at the end of the experiment. We took blood samples for Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), blood urea nitrogen (BUN), and creatinine (Cr) levels, and determined their values. The tissue samples were stained with hematoxylin/eosin to examine the renal changes histopathologically and stereologically under a light microscope. Results: Histopathological changes caused by I/R were decreased with vitamin A administration in a dose-dependent manner (p<0.05). Vitamin A administration decreased MDA levels and increased SOD and CAT activities (p<0.05). The most effective dose among treatment groups was 9000 IU/kg. There was no significant difference between the controls and all other groups regarding BUN and Cr concentrations. Conclusions: Consequently, administration of vitamin A after renal I/R reduced the histological damage and ameliorated the antioxidant state. These results showed that vitamin A could be a promising agent in treating I/R-induced acute kidney injury.
RESUMEN Introducción: La isquemia renal (I) puede desarrollarse debido a la disminución o interrupción del flujo sanguíneo al riñón en algunas condiciones clínicas como shock, sepsis y trasplante renal. El reabastecimiento de sangre al riñón se denomina reperfusión (R). Tanto la isquemia como los períodos de reperfusión pueden causar graves daños renales. Objetivos: Cuando examinamos la progresión molecular I/R, las moléculas antioxidantes como la vitamina A parecen agentes de tratamiento prometedores. El objetivo de este estudio fue investigar los efectos de la vitamina A sobre la lesión renal I/R. Material y Métodos: En el estudio, 40 ratas macho Sprague-Dawley se dividieron en 5 grupos (n=8) como: control, solo I/R, I/R+1000, I/R+3000 e I/R+9000 UI/kg de la Vitamina A. La vitamina A se administró a cada grupo durante 7 días por vía oral forzada. Al final del experimento se recolectaron muestras de sangre y tejido del riñón. A partir de muestras de sangre se determinaron los niveles de superóxido dismutasa (SOD), malondialdehído (MDA), catalasa (CAT), nitrógeno ureico en sangre (BUN) y creatinina (Cr). Las muestras de tejido se tiñeron con hematoxilina/eosina y los cambios en la histología renal se examinaron histopatológicamente y estereológicamente al microscopio de luz. Resultados: Los cambios histopatológicos causados por I/R disminuyeron con la administración de la vitamina A de manera dependiente de la dosis (p<0,05). La administración de la vitamina A disminuyó los niveles de MDA, aumentó las actividades de SOD y CAT (p<0,05). La dosis más eficaz entre los grupos del tratamiento fue de 9000 UI/kg. No hubo una diferencia significativa entre el grupo control y todos los demás grupos con respecto a las concentraciones de BUN y Cr. Conclusiones: Consiguientemente, la administración de la vitamina A, después de I/R renal, redujo el daño histológico y mejoró el estado antioxidante. Estos resultados mostraron que la vitamina A puede ser un agente promisorio en el tratamiento de la lesión renal aguda (LRA) inducida por I/R.
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OBJECTIVE: To determine the protective effects of a fungal metabolite of demethoxyviridine (DMV) and its derivative, 1-alpha-hydroxy-DMV in the livers of 2-month-old male Spraque-Dawley rats treated with diethylnitrosamine (DEN) and 2-acetylaminflourene (2-AAF). METHODS: This study was performed in the Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey from May 2006. Animals were divided into 10 groups. Those were the control, olive oil, dimethyl sulfoxide (DMSO), DMV, 1-alpha-hydroxy-DMV, DEN, 2-AAF, DEN+2-AAF, DEN+2-AAF+DMV, and DEN+2-AAF+1-alpha-hydroxy-DMV-treated animal groups. The liver microsomes were prepared from rats and the levels of expression of cytochrome P450 1A2 (CYP1A2) enzymes were determined with western blot technique. The liver tissue slides were evaluated histopathologically with hematoxylin and eosin staining and immunohistochemically for Harvey-retrovirus associated DNA sequences (Ha-Ras), glutathione S- transferase (GST-p), and connexion-32 (Cx32) proteins. RESULTS: Notably, there were no appreciable differences in CYP1A2 level among control, olive oil, and DMSO-treated animals. The CYP1A2 level was significantly decreased in 2-AAF, DEN+2-AAF, DEN, DEN+2-AAF+DMV, DEN+2-AAF+1-alpha-hydroxy-DMV, 1-alpha-hydroxy-DMV, and DMV-treated animals as compared to the control. Most prenoplastic focus was found in DEN+2-AAF treated group. CONCLUSION: Demethoxyviridine and 1-alpha-hidroksi-DMV had protective effect in the livers of DEN, 2-AAF and DEN+2-AAF induced rats.
