Título

EFFECTS OF ESCULIN TREATMENT ON P2X7RECEPTOR IN EXPERIMENTAL DIABETIC NEPHROPATHY

Introdução

Diabetes mellitus is a chronic disease, whichprogresses with manycomplications such asthe diabetic nephropathy (DN).P2X7 receptor is expressed in pathological conditions, in response to high concentrations of extracellular ATP, as seen in hyperglycemia. When constantly activated, P2X7can induce inflammatory responses, leading to oxidative stress(OS) and triggering toxic biochemical processes. Coumarin derivatives, such as esculin, are mainly antioxidants but their pharmacodynamics are not yet fully understood. Theaim of this study is to evaluate the effects of esculin on P2X7expression in the kidneys of diabetic rats.

Material e Método

In male Wistar rats 7 weeks old, diabetes was induced by a single dose of streptozotocin (60 mg/kg; i.v.); CTL group received only the vehicle. Diabetes was considered in animals withfasting glycaemia greater than 200 mg/dL, 48 hours after induction. Then, the animals received daily doses of esculin (50 mg/kg, p.o.) forming CTL+ESC and DM+ESC groups. 24-hours urine and a small aliquot of bloodvia retro-orbital plexus werecollected for biochemical analysis. The animals were euthanized under anesthesia, at the end of the eighth week of protocol and the kidneys were collected for Western blotting analysis,using antibodies against P2X7. The results are described as mean ± SEM; significance for p<0.05.

Resultados

The protein content of P2X7 was significantly decreased in the renal cortex of diabetic animals that received esculinwhen compared to untreated diabetic animals(0.76±0.11 vs 1.33±0.21). These animals also presented lower proteinuria (38.72±4.82 vs 45.42±3.0) and urinary TBARS excretion (232.3±28.83 vs 282.0±7.2), both p<0.05 compared with untreated diabetic animals.

Discussão e Conclusões

Our data suggest that esculin treatment decreases theP2X7 receptor in diabetic animals, accompanied by reduced OS and proteinuria, an early marker of DN, pointing to a new treatment that can be applied to control the evolution of this disease.

Palavras Chave

esculin, P2X7 receptor, diabetic nephropathy, oxidative stress Wistar rats.