Elsevier

Neuroscience

Volume 166, Issue 1, 10 March 2010, Pages 271-278
Neuroscience

Neuropharmacology
Research Paper
Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in streptozotocin-induced diabetic rat cerebral cortex

https://doi.org/10.1016/j.neuroscience.2009.12.028Get rights and content

Abstract

The mechanisms underlying diabetic encephalopathy, are largely unknown. Here, we examined whether docosahexaenoic acid (DHA) and lutein could attenuate the oxidative changes of the diabetic cerebral cortex. The levels of malondialdehyde (MDA) were significantly increased and glutathione (GSH) and glutathione peroxidase activity (GPx) were decreased in diabetic rats. The number of 4-hydroxynonenal (4-HNE) positive cells was increased. Treatment with insulin, lutein or DHA and the combination of each antioxidant with insulin, significantly restored all markers concentrations mentioned above, and the increase in 4-HNE inmunofluorescence. We combined 4-HNE immunofluorescence with NeuN (Neuronal Nuclei) staining. The latter demonstrated extensive overlap with the 4-HNE staining in the cortex from diabetic rats. Our findings demonstrate a clear participation of glucose-induced oxidative stress in the diabetic encephalopathy, and that the cells suffering oxidative stress are neurons. Lowering oxidative stress through the administration of different antioxidants may be beneficial for the central nervous tissue in diabetes.

Section snippets

Experimental design

Male Wistar rats were used in the study. Diabetes was induced in animals by a single i.p. injection of STZ (65 mg/kg) in 0.1 M citrate buffer, pH 4.5. Another set of rats, which received only vehicle, served as the control. Fasting blood glucose levels were measured 72 h after STZ injection. Animals having blood glucose levels>200 mg/dl were considered diabetic. Animals were randomly divided into the following experimental groups: control rats (group C); control animals treated with lutein (0.5

Results

Table 1 shows body weight, blood glucose and glycated haemoglobin levels of diabetic and age-matched control rats. The body weight of STZ diabetic rats was significantly lower than that of controls, 3 months after injection of STZ. Blood glucose and HbA1c levels differed significantly between diabetic and control mice and treatment with lutein and DHA did not affect these values. Insulin administration to diabetic rats significantly reversed all these changes to near normal levels.

Discussion

Streptozotocin-induced diabetes is a well-documented model of experimental diabetes that provides a relevant example of endogenous chronic oxidative stress as a result of hyperglycemia (Low et al., 1997). In the present study, STZ treatment produced significant increase in glucose levels along with reduction in body weight in diabetic animals. In addition, there was marked increase in water intake (data not shown) and polyuria which are hallmark clinical findings in diabetes. On the other hand,

Conclusion

In conclusion, this study shows neuroprotective effect of two treatments, lutein and DHA, in cortical neurons of diabetic animals. Further research is needed on the neuroprotective effect of lutein and DHA in relationship to apoptosis and cell survival in cerebral cortex in the diabetic condition.

Acknowledgments

Partially supported by the project PI03/1710 from FIS to F.B.-M., and PRUCHA06/29 from FUSP, and Copernicus-Santander program to F.J.R. We thank David Smith (Oxford University) for his careful reading and correction of the manuscript.

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