Original articleEvaluation of the effect of oxidative stress and vitamin E supplementation on renal function in rats with streptozotocin-induced Type 1 diabetes
Introduction
At least 25% of patients with Type 1 diabetes mellitus (DM) and 30% to 40% of patients with Type 2 DM eventually develop diabetic nephropathy that may progress to end-stage renal disease (ESRD) (United States Renal Data System (USRDS), 2000, Ritz et al., 1997). As Type 1 DM usually manifests early in life, ESRD may develop at a younger age producing an additional burden for patients and health services (Mauer, Fioretto, Woredekal, & Friedman, 2001).
In diabetic nephropathy, structural injury develops over years before clinical and laboratory abnormalities such as albuminuria, hypertension, or declining glomerular filtration rate appear (Caramori et al., 2002). The earliest clinical manifestations of diabetic nephropathy often represent already well-established renal injury (Mauer & Drummond, 2002). Thus, waiting for clinical or laboratory manifestations of renal disease before initiating treatment may hinder efforts to prevent progression to ESRD.
Several pathways are thought to be involved in the pathogenesis of hyperglycemia-induced complications in DM such as activation of protein kinase C isoforms, increased formation of advanced glycation end products (AGEs), and increased flux through the aldose reductase pathway (Ishii et al., 1996). Interestingly, the excessive production of reactive oxygen species (ROS) has been suggested as a common product of all these pathways that can result in the DM-associated complications (Ishii et al., 1996).
We evaluated the role of ROS in the induction of diabetic nephropathy as well as the potential protective effect of vitamin E supplementation in diabetic animals. We measured markers of oxidative stress and antioxidant state and parameters of kidney function after various treatment protocols in a streptozotocin-induced rat diabetic model.
Section snippets
Experimental animals
This study involved 42 male albino rats weighing between 170 and 200 g. The animals were randomly divided into seven groups each consisting of six rats. Animals were fed a standard diet and housed in the animal house of Kasr Al-Aini Faculty of Medicine with a 12:12-h light/dark cycle. DM was induced by an intraperitoneal (ip) injection of streptozotocin (40 mg/kg in freshly prepared citrate buffer pH 4.5). Control rats were injected with vehicle alone. DM was verified 48 h later by measuring
Statistical methods
Data are presented as mean±S.D. Comparisons were made using paired and unpaired t test, one-way ANOVA, or repeated-measures ANOVA, where appropriate. P<.05 was considered significant.
Blood pressure measurements
There was a significant increase in both systolic and diastolic blood pressure in diabetic animals when compared with controls.
Treatment of diabetic animals with insulin (Group III) or vitamin E at the 300 mg/kg dose significantly reduced blood pressure values when compared with the untreated diabetic group to almost control levels (P<.0001). Vitamin E at the 600 mg/kg dose in Group V significantly lowered blood pressure measurements to values even lower than those obtained in the control group
Discussion
Our results showed that untreated diabetic animals had a significant increase in blood pressure when compared with controls 4 weeks after induction of DM. Hypertension is frequently seen in Type 1 DM and its pathogenesis is multifactorial. For example, alterations in the renin–angiotensin system, decreased availability of nitric oxide (NO), dyslipidaemia, as well as increased production of ROS may be involved (Haidara, Yassin, Rateb, Ammar, & Zorkani, 2006).
The treatment of diabetic animals
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