Physiological variation in plasma total homocysteine concentrations in rats

Martins, Paulo S.; Galdieri, Luciano; Souza, Fernanda; Andersen, Mônica Levy; Benedito‐Silva, Ana Amélia; Tufik, Sérgio; D’Almeida, Vânia

doi:10.1016/j.lfs.2004.12.011

Cited by 22 publications

(10 citation statements)

References 33 publications

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“…In the CT group, a significant decrease could be associated with the increase in animal age. This effect has already been described in rats by our group [30] and is the opposite of the effect reported in humans [31], [32]. Moreover, it is interesting to note that this decrease in Hcy concentrations over time was not observed in the treated groups, suggesting that an augmentation induced by methionine treatment in fact coped with the physiological decrease observed in aged animals.…”

Section: Discussionmentioning

confidence: 40%

Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice

Rezende

D’Almeida

2014

PLoS ONE

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Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric disorders, but the mechanisms involved in this process have not been completely elucidated. The aim of this study was to analyze the influence of hyperhomocysteinemia induction by methionine supplementation considering different levels and periods of exposure in mice. For this purpose, methionine supplementation at concentrations of 0.5 and 1% were administered in water to increase homocysteinemia in male C57BL/6 mice, and was maintained for 3 time periods (2, 4 and 6 months of treatment). The results from one-carbon metabolism parameters, brain-derived neurotrophic factor (BDNF) concentrations and behavioral evaluation were compared. The 0.5% supplementation was efficient in increasing plasma homocysteine levels after 2 and 6 months. The 1% supplementation, increased plasma homocysteine after 2, 4 and 6 months. Little influence was observed in cysteine and glutathione concentrations. Frontal cortex BDNF levels showed a lack of treatment influence in all periods; only the expected decrease due to increasing age was observed. Moreover, the only behavioral alteration observed using a novel object recognition task was that which was expected with increasing age. We found that responses to hyperhomocysteinemia varied based on how it was reached, and the length of toxicity. Moreover, hyperhomocysteinemia can affect the normal pattern of one carbon metabolism during age increase in mice. These findings allow the establishment of a reliable animal model for studies in this field.

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Section: Discussionmentioning

confidence: 40%

Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice

Rezende

D’Almeida

2014

PLoS ONE

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“…In a study related to the circadian rhythm of Hcy in humans [22], the highest levels were reported at around 22:00, gradually decreasing thereafter to the lowest levels at around 10:00. Other research reported the highest Hcy levels in rats at night around 02:00, which are different from those in humans [24]. These results show that the homocysteine rhythm is different in rats and humans.…”

Section: Discussioncontrasting

confidence: 58%

“…The few that are available deal with the physiological range of Hcy and its variations in relation to some pathologies [19] and the influence of a single exercise test, but not training, on the plasmatic levels of homocysteine [20]. As for studies on daily rhythm in men [21][22][23] and rats [24,25], it is evident that the rhythmicity of the parameter and the influence of physical exercise have been considered only together, never separately. It is known that many circadian rhythms in physiological functions are evident under resting conditions and that these rhythms are influenced by physical exercise [26].…”

Section: Homocysteine (Hcy) Is a Sulfur Intermediate Amino Acidmentioning

confidence: 99%

The Influence of Exercise on the Daily Rhythm of Serum Homocysteine in Horses

et al. 2006

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Abstract:The aim of this study was to determine the daily rhythms in the blood serum of homocysteine in horses. Ten thoroughbred horses, five athletic (trained for 1 h, 6 days a week) and five sedentary, were used. Blood samples were collected on each subject every 4 h for two days by means of the jugular vein. On each individual sample, the serum concentration of homocysteine was assessed. The results obtained during the experimental period indicated the existence of a daily rhythm of serum homocysteine in sedentary and athletic horses. They also demonstrated that in horses, physical exercise influences the daily rhythm of serum homocysteine.Key words: circadian rhythms, homocysteine, horse.Homocysteine (Hcy) is a sulfur intermediate amino acid in methionine-cysteine metabolism [1]. The importance of this metabolic pathway relates to the sheer number of physiological functions in which it is involved; it contains the methyl donor (S-adenosyl-methionine) for virtually all methylation reactions in the organism [2] and provides the limiting substrate (cysteine) for the synthesis of glutathione [3]. The metabolism of Hcy leads to three possible main outcomes: it may be remethylated to methionine, converted to cysteine by transulfuration, or exported to the extracellular space. In man, moderately increased concentrations of total homocysteine (tHcy) have been identified as an independent risk factor for cardiovascular disease (CVD), stroke, and other thrombotic events [4][5][6][7][8][9][10][11], as well as increased concentrations of total cysteine (tCys) [12]. Regular physical exercise is now recognized to reduce the risk of CVD development [13,14]. Sedentary subjects, however, are considered to be at risk for CVD. Although available evidence indicates that physical activity modifies the lipid and carbohydrate metabolism [15], non energetic exercise-induced metabolism stress has not been extensively studied [16]. Recent data have pointed out that the duration and intensity of exercise are relevant factors in modulating the plasma Hcy levels. Bailey et al. [17] have shown that a 4-week exercise program was associated with a reduction in Hcy levels in healthy men, whereas Nygard et al. [18] confirmed that a lack of exercise might be partly associated with elevated plasma tHcy levels, increasing the risk of CVD in the elderly. As far as horses are concerned, there are not many studies on homocysteine, neither on the effects derived from training nor on its daily rhythm. The few that are available deal with the physiological range of Hcy and its variations in relation to some pathologies [19] and the influence of a single exercise test, but not training, on the plasmatic levels of homocysteine [20]. As for studies on daily rhythm in men [21][22][23] and rats [24,25], it is evident that the rhythmicity of the parameter and the influence of physical exercise have been considered only together, never separately. It is known that many circadian rhythms in physiological functions are evident under resting conditions and tha...

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“…Only limited studies with small sample sizes and without taking gender differences into account have analyzed circadian rhythms of homocysteine levels (Guttormsen et al, 2004;Jordan et al, 2004;Lavie & Lavie, 2004, 2006. In rats, plasma homocysteine concentration varies spontaneously with ontogenic development and during the estrous cycle, and shows 24 h variation in young rats with lower levels during the night (Martins et al, 2005). The disruption of the circadian rhythm as found in shift workers is related to disturbances in homocysteine metabolism, with homocysteine levels being about twice as high as compared to day workers (Martins et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Daily Variations of Homocysteine Concentration May Influence Methylation of DNA in Normal Healthy Individuals

Bönsch

Hothorn

Krieglstein

et al. 2007

Chronobiology International

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The regulation of genetic expression is tightly controlled and well balanced in the organism by different epigenetic mechanisms such as DNA methylation and histone modifications. DNA methylation occurring after embryogenesis is seen mainly as an irreversible event. Even small changes in genomic DNA methylation might be of biological relevance, and several factors influencing DNA methylation have been identified so far, one being homocysteine. In this study, genomic DNA methylation was analyzed and homocysteine plasma levels were measured over a 24 h period in 30 healthy students (15 males and 15 females) exposed to a standard 24 h regime of daytime activity alternating with nighttime sleep. Plasma homocysteine concentrations were measured using HPLC detection. DNA was extracted from whole EDTA blood, and genomic DNA methylation was assessed by fluorescently labeled cytosine extension assay. Both homocysteine and DNA methylation showed 24 h variation. Homocysteine showed a significant daily rhythm with an evening peak and nocturnal nadir in all subjects (p<0.001). Males showed higher overall homocysteine levels compared to females (p=0.002). Genomic DNA methylation showed a significant rhythm with increased levels at night (p=0.021), which was inverse to plasma homocysteine levels.

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Physiological variation in plasma total homocysteine concentrations in rats

Cited by 22 publications

References 33 publications

Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice

Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice

The Influence of Exercise on the Daily Rhythm of Serum Homocysteine in Horses

Daily Variations of Homocysteine Concentration May Influence Methylation of DNA in Normal Healthy Individuals

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