DRAGONFLY KINGDOM NTERNATIONAL SERVICE AGENCY

Abstract

Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar β-adrenergic receptor function. We examined whether this effect was related to the antioxidant capacity of the food supplement and whether an antioxidant-rich diet reduced the levels of proinflammatory cytokines in the cerebellum. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage or supplied in the rat chow daily for 14 d.

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Electrophysiologic techniques revealed a significant decrease in β-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple (a food with intermediate ORAC) had an intermediate effect on cerebellar β-adrenergic receptor physiology, and cucumber (low ORAC) had no effect, indicating that the reversal of β-adrenergic receptor function decreases might be related to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis factor-α (TNFα) and TNFβ was also examined. RNase protection assays revealed increased levels of these cytokines in the aged cerebellum.

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Spirulina and apple significantly downregulated this age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that one mechanism by which these diets work is by modulation of an age-related increase in inflammatory responses. Malondialdehyde (MDA) was measured as a marker of oxidative damage. Apple and spirulina but not cucumber decreased MDA levels in the aged rats. In summary, the improved β-adrenergic receptor function in aged rats induced by diets rich in antioxidants is related to the ORAC dose, and these diets reduce proinflammatory cytokine levels.

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Impaired antioxidant defense mechanisms and increases in reactive oxygen species and reactive nitrogen species are postulated to be causative factors in aging-related functional declines and in neurodegenerative diseases (Harman, 1956; Leibovitz and Siegel, 1980; Ames et al., 1993). Increasing evidence suggests that inflammatory processes are linked to oxidative damage in the CNS. Injection of the antioxidant enzyme superoxide dismutase decreases inflammation in some animal model systems.

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Antioxidants such as vitamins E, C, and β-carotene enhance some parameters of immune function when added to isolated immune cellsin vitro or when given as supplements to humans or animalsin vivo (Han and Meydani, 2000). Despite extensive evidence of the anti-inflammatory effects of antioxidants, little is known about the underlying molecular mechanisms.

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One potential mechanism is the effect of antioxidants on the production of immunoregulatory molecules such as cytokines. Cytokines are induced in response to brain injury and can mediate and inhibit cellular injury and repair. Many clinical studies report increased cytokine expression in the CSF or in postmortem brain tissue of patients that have suffered stroke or brain injury. Several lines of evidence indicate that proinflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor-β increase with aging (Lynch, 1998; Knoblach et al., 1999

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Several studies have examined antioxidants and their effects in aged animals and humans. Diets enriched in fruits and vegetables that have a high antioxidant capacity as measured by oxygen radical absorbance capacity (ORAC) (Cao et al., 1997) fed to rats for periods as short as 2 weeks to 2 months starting at 18 months of age can reverse the age-related onset of some behavioral and neurochemical deficits (Gould and Bickford, 1997; Joseph et al., 1999; Bickford et al., 2000). Much of the evidence supporting the beneficial role of fruits and vegetables to health comes from epidemiological literature.

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The traditional common diet of the Mediterranean region, a diet high in fruits and vegetables, is associated with a significant (17%) reduction in overall mortality in the elderly from these regions (Willet et al., 1995). Recent studies with vitamin E indicate that high doses slow the progression of certain aspects of Alzheimer's disease (Sano et al., 1997). Vitamin E 1300 IU Oil

The nature of the protective effects of specific nutrients found in fruits and vegetables, such as β-carotene, vitamin C, and vitamin E, however, is unknown.

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A single factor is not likely to be the only effective agent in these studies. With few exceptions, a single nutrient is not packaged into a single food, and it is possible that combinations of nutrients have greater protective effects than each nutrient alone.......

Indexed for Journal of Neuroscience by Dragonfly Kingdom Library

https://www.jneurosci.org/content/22/14/6114