Hypothalamic superoxide dismutase, xanthine oxidase, nitric oxide, and malondialdehyde in rats fed with fish ω-3 fatty acids

doi:10.1016/j.pnpbp.2004.05.006

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 28, Issue 4, July 2004, Pages 693-698

https://doi.org/10.1016/j.pnpbp.2004.05.006 Get rights and content

Abstract

Phospholipids located in the cellular membrane play a critical role in the fluid-mosaic model of membrane structure and membrane function. Evidence is mounting for the role of abnormal phospholipid metabolism in some neuropsychiatric disorders including schizophrenia. As an important essential fatty acid (EFA), omega-3 (ω-3) fatty acid series are found in large amounts in fish oil. The aim of this experimental study was to assess the changes of some of the oxidant and antioxidant parameters in the hypothalamus of rats fed with ω-3 EFA diet (0.4 g/kg/day) for 30 days. Eight control rats and nine rats fed with ω-3 were decapitated under ether anesthesia, and hypothalamus was removed immediately. Malondialdehyde (MDA) and nitric oxide (NO) levels as well as superoxide dismutase (SOD) and xanthine oxidase (XO) enzyme activities in the hypothalamus were measured. SOD activity was significantly decreased in ω-3 EFA treated group compared to control group (p<0.014). Tissue MDA and NO levels were also decreased in ω-3 EFA treated group compared to control rats (p<0.0001). Xanthine oxidase activity was found to be increased in ω-3 EFA treated rats when compared to the control group (p<0.0001). Taken together, this preliminary animal study provides strong support for a therapeutic effect of ω-3 EFA in some neuropsychiatric disorders in which reactive oxygen species (ROS) are recently accused to be an important physiopathogenetic factor.

Introduction

Omega-3 essential fatty acids (ω-3 EFA) include α-linolenic acid (all-cis-9,12,15-Octadecatrenoic acid), timnodonic acid (all-cis-5,8,11,14,17-Eicosapentaenoic acid), and cervonic acid (all-cis-4,7,10,13,16,19-Docosahexaenoic acid). Dietary provision of long-chain ω-3 EFA is essential because mammals are incapable of synthesizing fatty acids with a double bond past the Δ−9 position. Therefore, dietary intake of ω-3 EFA has far reaching consequences on fluid mosaic model of membrane composition in all cells in the body and may influence neural function as well. Behavioral abnormalities in animals consuming diets unbalanced in polyunsaturated fatty acids (PUFA) were observed (Wainwright et al., 1997) and abnormal polyunsaturated fatty acids (PUFA) levels in some biological samples such as erythrocytes, plasma, and postmortem brain tissues were found in some neuropsychiatric disorders such as schizophrenia and autism Glen et al., 1994, Horrobin et al., 1989, Yao et al., 1994. On the other hand, learning ability was found to be significantly reduced in ω-3 EFA deficient rats (Takeuchi et al., 2002).

Erythrocyte lipid peroxidation levels in patients with schizophrenia were found to be increased three- to four-fold compared to healthy controls (Herken et al., 2001). Reduced levels of phospholipids and PUFAs in erythrocyte membranes (Keshevan et al., 1993) and brain homogenates (Horrobin et al., 1991), and increased levels of lipid peroxidation end products in schizophrenia Herken et al., 2001, Akyol et al., 2002 may clearly show that there is a direct relationship between membrane phospholipid abnormalities and lipid peroxidation. In the other words, one of the mechanisms implicated in the phospholipid abnormalities and consequently in neuronal damage is the formation of reactive oxygen species (ROS) in some neuropsychiatric disorders.

In the central nervous system (CNS), dopamine is involved in the control of locomotion, cognition, affect and neuroendocrine secretion. Dopamine released from the hypothalamus controls the synthesis and secretion of prolactin from the anterior pituitary via D2 dopamine receptors. However, there is a substantive literature on the hypothalamic-pituitary abnormalities in schizophrenia. In most psychiatric disorders, stress is the major nongenomic factor that contributes to the expression or exacerbation of acute symptoms, recurrence or relapse after a period of remission, and treatment outcome (Moghaddam, 2002). On the other hand, the basis of glial cell loss in some neuropsychiatric disorders suggest that elevated levels of glucocorticoids, due to illness-related stress or to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) may down-regulate glial activity and so predispose to, or exacerbate psychiatric illness through enhanced excitotoxicity (Cotter et al., 2001).

The rat brain can be regarded as a useful model in vivo, because of its high susceptibility to oxidative damage (Arivazhagan et al., 2002). Therefore, we aimed to investigate the possible protective role of ω-3 EFA on rat hypothalamus as a preliminary study prior to the experimental psychosis model studies, which will be investigated by our research team, in rats. To better understand the biochemical effects of ω-3 EFA on the hypothalamic oxidant and antioxidant parameters, we focused our attention to their effects on the activities of superoxide dismutase (SOD) and xanthine oxidase (XO) as well as the levels of nitric oxide (NO) and malondialdehyde (MDA) using spectrophotometric methods.

Section snippets

Animals

Adult male albino Wistar rats (mean weight 250±5 g) were obtained from Firat University Biomedical Research Unit of the Institute of Health Sciences and divided into two groups. Saline was given to the Control group (n=8) by gavage and ω-3 EFA (0.4 g/kg/day, Marincap capsule®) was given to the treatment group (n=9) for 30 days. The composition of the Marincap 500 mg capsule contains eicosapentaenoic acid (EPA; 18%) and docosahexaenoic acid (DHA; 12%) with additional artificial antioxidant

Results

Results were summarized in Fig. 1. According to this figure, SOD activity was significantly decreased in ω-3 EFA treated group (0.49±0.06 U/mg prot.) compared to control group (0.58±0.07 U/mg prot.; p<0.014). Tissue MDA and NO levels were also decreased in ω-3 EFA treated group (23.02±10.14 nmol/g wet tissue and 1.06±0.14 μmol/g wet tissue, respectively) compared to control rats (66.37±22.73 nmol/g wet tissue and 1.57±0.22 μmol/g wet tissue, respectively). P values were <0.0001 for both MDA and

Discussion

The present study shows that dietary ω-3 EFA supplementation can affect the antioxidant system and lipid peroxidation processes of rat hypothalamus. These results are consistent with our earlier report on the effect of dietary ω-3 EFA on hippocampus (Sarsilmaz et al., 2003a) and corpus striatum (Sarsilmaz et al., 2003b). Interestingly, Newman et al. (2003) demonstrated that dietary ω-3 and 6 fatty acids alter avian pituitary sensitivity and this modulation is determined by the nature of the

Conclusion

Supplementation of ω-3 EFA to the regular rat diet may protect membranous structures from lipid peroxidation and enhance antioxidant defence system. The second step of this preliminary animal study will be the investigation of the protective effect of ω-3 EFA on biochemical parameters of different brain regions as well as behavioral and physiological characteristics in a rat psychosis model.

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Hypothalamic superoxide dismutase, xanthine oxidase, nitric oxide, and malondialdehyde in rats fed with fish ω-3 fatty acids

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Conclusion

Prog. Neuro-Psychopharmacol. Biol. Psychiatry

Eur. Neuropsychopharmacol.

J. Nutr. Biochem.

Brain Res. Bull.

Arch. Biochem. Biophys.

Neurol. Clin.

Schizophr. Res.

Biol. Psychiatry

Biol. Psychiatry

Neuropharmacology

J. Biol. Chem.

Prostaglandins Leukot. Essent. Fat. Acids

Prog. Neuro-psychopharmacol. Biol. Psychiatry

Psychiatr. Clin. North Am.

Biol. Psychiatry

Brain Res.

Psychiatry Res.

FEBS Lett.