Exogenous SOD Mimetic Tempol Ameliorates the Early Retinal Changes Reestablishing the Redox Status in Diabetic Hypertensive Rats

Abstract

The administration of tempol prevented oxidative damage, decreased iNOS levels, and ameliorated the activation of PARP in the retinas of diabetic hypertensive rats. Consequently, the early molecular markers of DR, such as glial reaction (glial fibrillary acidic protein [GFAP]) and extracellular matrix accumulation (fibronectin), were prevented in tempol-treated rats.

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

“…155 Consumption of dark chocolate is associated with blood pressure reduction associated with a reduction in oxidative stress and increase in nitric oxide bioavailability, 156 both abnormalities that have been involved in the pathogenesis of diabetic nephropathy and retinopathy. 67,[85][86][87][88][93][94][95][97][98][99]156 Finally, in experimental diabetes, the use of green tea was associated with an improvement in diabetic nephropathy and retinopathy and associated with a reduction in oxidative stress. 91, 157 The usefulness of these dietary approaches in diabetic patients with hypertension and nephropathy or retinopathy that are on standard treatment deserves to be tested in larger clinical trials.…”

“…84 In the retina, a number of studies have shown that there is an increase in oxidative markers after the induction of DM, 67,[93][94][95] but the concomitance of diabetes and hypertension evoked earlier oxidative retinal damage characterized by an increase in nitrotyrosine and 8-OHdG in retinal tissue from short-term STZ-induced DM in SHRs. [96][97][98][99] These oxidative markers were the consequence of an increase in superoxide production and depletion of the gluthationereduced antioxidant system in the retinal tissue. [96][97][98] Interestingly, the administration of a superoxide dismutase mimetic tempol to diabetic SHRs re-established the redox status and improved early molecular markers of DR. 97 In these models, with long-term diabetes (12 weeks of duration), we have demonstrated that hypertension could account for exacerbation of retinopathy in diabetic SHRs.…”

“…[96][97][98][99] These oxidative markers were the consequence of an increase in superoxide production and depletion of the gluthationereduced antioxidant system in the retinal tissue. [96][97][98] Interestingly, the administration of a superoxide dismutase mimetic tempol to diabetic SHRs re-established the redox status and improved early molecular markers of DR. 97 In these models, with long-term diabetes (12 weeks of duration), we have demonstrated that hypertension could account for exacerbation of retinopathy in diabetic SHRs. It was observed that higher levels of apoptotic neural cells were found in retinas from diabetic SHR, accompanied by increased glial reaction, both of which are accepted as early markers of DR.…”

Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart

“…Animals were housed in the Division of Laboratory Animal Resources until the day of study. Each rat was randomized to receive or not receive a daily intraperitoneal injection of Tempol (125 mg·kg Ϫ1 ·day Ϫ1 ) dissolved in saline solution (125 mg/ml) each morning (9:00 -10:00 AM) (18,54). In the control groups, rats received intraperitoneal injection of saline solution (1 ml/kg) each day.…”

Age-dependent neuroprotection of retinal ganglion cells by tempol-C8 acyl ester in a rat NMDA toxicity model

“…Tempol and its derivative tempol hydroxylamine also acted neuroprotectively in models of light damage [26]. Unfortunately, tempol is effective only in relatively high doses; some authors have reported effective doses of ≥ 100 mg/kg body weight in in vivo situations [18]. Such high doses in conscious animals have been reported to trigger serious side effects, including seizures, hypotension, and agitation [7].…”