The influence of sleep deprivation and obesity on DNA damage in female Zucker rats.

OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Influence of acute sleep deprivation on cardiovascular parameters in female Zucker obese and lean rats.

OBJECTIVE: There is a reciprocal relationship between sleep duration and weight gain. However, the consequences of this relationship on the cardiovascular system over an entire life span are still not fully elucidated. We examined the effect of acute sleep deprivation (SD) on baroreflex sensitivity and blood pressure in Zucker rats of different ages. DESIGN AND METHODS: Female lean and obese Zucker rats at 3, 6 and 15 months of age were assigned to SD or control (CTRL) groups. After a 6 h period of the SD procedure (6 h of gentle handling) or CTRL procedure (an equivalent period without handling), the animals were anesthetized for surgical catheterization of the femoral artery and vein. To evaluate the baroreflex sensitivity index, bolus infusions of phenylephrine (bradycardia response) and sodium nitroprusside (tachycardia response) were administered. RESULTS: Obesity resulted in dysfunctional tachycardia responses at 3 months of age. At 6 and 15 months of age, both bradycardia and tachycardia responses were significantly lower in obese animals than those in lean animals. At 15 months of age, interactions among obesity, SD and aging produced the most marked effects on the cardiovascular system (increased mean arterial pressure and heart rate and decreased baroreflex sensitivity). CONCLUSIONS: Therefore, these results suggest that there is no direct relationship between baroreflex imbalance and an increase in arterial pressure.

More than hormones: sex differences in cardiovascular parameters after sleep loss in rats.

Although the influence of sex on sleep pattern and cardiovascular parameters is well known, knowledge regarding the effects of sleep loss on heart responses in both sexes is scarce. The present study investigated the effects of paradoxical sleep deprivation (PSD) and chronic sleep restriction (SR) on cardiovascular parameters and adrenocorticotropic hormone (ACTH) levels in male and female rats. Both groups were randomly assigned to PSD for 96 h, SR for 21 days or home-cage control. Mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity (bradycardia and tachycardia responses) and ACTH levels were evaluated. The results showed that PSD induced a significant increase in HR and ACTH levels in both sexes, although male rats presented higher levels of ACTH hormone compared to females. In addition to sex-specific responses, PSD decreased the tachycardia only in male rats. SR, induced a significant increase in MAP and decrease in bradycardia in both sexes. Male rats were more affected by sleep deprivation protocols than females for MAP, bradycardia response, and ACTH levels. The results showed that the effects of sleep loss on cardiovascular parameters are associated with the protocol of sleep deprivation and that sex can modulate these effects. We suggested this experimental model as a suitable tool for further investigations of the relationship between cardiovascular parameters and sleep.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Protective effects of green tea against hepatic injury induced by high-cholesterol diet in rats: histopathological analysis, oxidative DNA damage and COX-2 expression.

PURPOSE: The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. METHODS: Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. RESULTS: The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p > 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p < 0.05) in the mean tail moment between groups treated with green tea and cholesterol and cholesterol only. Furthermore, histomorphometric analysis of COX-2 expression revealed that in groups exposed to green tea they were significantly decreased (p < 0.05), regardless of time exposure adopted. CONCLUSION: Taken together, our results suggest that daily administration of green tea for at least 7 days displays some preventive properties as indicated by COX-2 downregulation and decreased oxidative DNA damage.

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones.