A hipertensão arterial exacerba o estresse oxidativo em retina de ratos experimentalmente diabeticos / Arterial hypertension exarcebates oxidative stress in retina of experimentally diabetic rats

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

The presence of arterial hypertension in patients with diabetes mellitus (DM) is identified as the most important independent risk factor for progression of diabetic retinopathy (DR). Independently, diabetes and hypertension increase oxidative stress in the retina both humans and animals. However, the effect of the combination of both hypertension and DM in the retina was never addressed. Therefore, the aim of this study was to investigate the oxidative stress in the retina of an experimental model that combines hypertension and DM. Four week old spontaneously hypertensive rats (SHR) and their normotensive counterpart Wystar Kyoto (WKY) rats were rendered diabetic by intravenous injection of streptozotocin. After 20 days, the rats were sacrificed and the eyes and retinas were collected. The production of superoxide evaluated by enhanced lucigenin method was higher in diabetic than the control WKY (p<0.03) and the SHR rats showed elevated superoxide production in both control and diabetic groups compared with non diabetic WKY (p<0.009). The antioxidant defense system of glutathione (reduced form, GSH), was significantly diminished only in diabetic SHR (p<0.04). Tirosyne nitration evaluated by immunohystochemistry for nitrotyrosine (NT) was equally elevated in both diabetic WKY and control SHY compared with control WKY (p<0.03) and further increment was observed in diabetic SHR group (p<0.02). The DNA damage due oxidative stress evaluated by immunohystochemistry for 8-hydroxy-2?-deoxyguanosine (8-OHdG) was higher in control SHR than in control WKY (p=0.0003) and further increment was detect in diabetic SHR rats (p<0.0001). The NADPH oxidase activity, evaluated by the retinal expression of gp91phox and NOX-4, was not altered in the retina from hypertensive and diabetic rats. The expression of AGE-receptor (RAGE) was not altered. Western blot assay for NF-kB showed increased in control and diabetic SHR rats. Diabetes determines an early unbalance between oxidant and antioxidant systems leading to damage in the retina and the presence of hypertension exacerbates this effect. These abnormalities may contribute to mechanism by which the hypertension aggravates RD.

ASSUNTO(S)

estresse oxidativo diabetes mellitus hipertensão hypertension oxidative stress diabetic nephropathy retinopatia diabetica

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