Original article
Evaluation of the effect of oxidative stress and vitamin E supplementation on renal function in rats with streptozotocin-induced Type 1 diabetes

https://doi.org/10.1016/j.jdiacomp.2008.02.011Get rights and content

Abstract

We investigated the possible role of reactive oxygen species (ROS) on renal function in experimental diabetes.

Materials and Methods

Seven groups of male rats were studied. Group I consisted of control animals. Diabetes was induced (by streptozotocin) in the animals in the other groups and they received either insulin or vitamin E (300 or 600 mg/kg), both insulin and vitamin E, or no treatment for 4 weeks. At the end of the study, blood pressure was measured and parameters of kidney function and oxidative stress were evaluated in serum and kidney tissue samples.

Results

Diabetic animals had higher blood pressures; increased serum glucose, urea, creatinine, cyclic guanosine monophosphate (cGMP); increased kidney tissue levels of malondialdehyde and inducible nitric oxide synthetase (iNOS); and reduced serum glutathione peroxidase when compared with control animals. Blood glucose levels in diabetic animals were controlled by insulin and not by any dose of vitamin E alone. However, all other measured parameters improved towards control levels with either insulin or vitamin E in either dose. An additive beneficial effect was observed on the levels of iNOS and cGMP when both forms of treatment were used in diabetic animals.

Conclusions

We conclude that ROS may play an important role in diabetes-induced nephropathy in this rat model. Vitamin E supplementation in addition to insulin can have additive protective effects against deterioration of renal function in this model.

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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