Gastroprotective effect of leaf extract of two varieties grapevine (Vitis vinifera L.) native wild and cultivar grown in North of Tunisia against the oxidative stress induced by ethanol in rats.

Context: Vitis vinifera leaves are traditionally used in Tunisian folk medicine to treat digestive pathologies.Objective: We aimed to compare the gastroprotective effects of hydromethanolic leaves extracts of wild and cultivated grapes accessions native of Tunisia.Materials and methods: The phytochemical analysis of grapevine leaves extracts was performed. The gastroprotective activity was evaluated by ethanol-induced gastric-ulcer in rats pre-treated with increased doses of the extracts or with the standard omeprazole. Index of gastric secretions (volume, pH and gastric mucus production), stomach wall histology and biochemical parameters were estimated for assessment of anti-secretory and gastroprotective effects of the extracts.Results: Pre-treatment with grapevine leaves extracts decreased significantly gastric volume, gastric mucosal damage and increased significantly gastric juice pH compared with the negative control group. The extracts prevented ethanol-induced decrease of the activity of antioxidant enzymes while the levels of malondialdehyde and of reduced glutathione were decreased significantly. Moreover, the most marked effect was observed at low doses of wild ecotype 'Nefza-I' extracts.Conclusion: The leaves of Vitis species might be suitable as a functional food for therapeutic purpose and demonstrates gastroprotective action in gastric lesions model. Both accessions exhibited gastroprotective effects, but wild 'Nefza-I' ecotype was more effective than cultivar 'Marsaoui'.

Blooming rhythms of cactus Cereus peruvianus with nocturnal peak at full moon during seasons of prolonged daytime photoperiod.

Cereus peruvianus (Peruvian apple cactus) is a large erect and thorny succulent cactus characterized by column-like (cereus [L]: column), that is, candle-shaped, appendages. For three successive years (1100 days), between early April and late November, we studied the flowering patterns of eight cacti growing in public gardens and rural areas of north and central Tunisia, far from nighttime artificial illumination, in relation to natural environmental light, temperature, relative humidity and precipitation parameters. Flower blooming was assessed nightly between 23:00 h and until at least 02:00 h, and additionally around-the-clock at ~1 h intervals for 30 consecutive days during the late summer of each year of study to quantify both nyctohemeral (day-night) and lunar patterns. During the summer months of prolonged daytime photoperiod, flower blooming of C. peruvianus exhibited predictable-in-time variation as "waves" with average period of 29.5 days synchronized by the light of the full moon. The large-sized flower (~16 cm diameter) opens almost exclusively at night, between sunset and sunrise, as a 24 h rhythm during a specific 3-4-day span of the lunar cycle (full moon), with a strong correlation between moon phase and number and proportion of flowers in bloom (ranging from r = +0.59 to +0.91). Black, blue and red cotton sheets were used to filter specific spectral bands of nighttime moonlight from illuminating randomly selected plant appendages as a means to test the hypothesis of a "gating" 24 h rhythm phenomenon of photoreceptors at the bud level. Relative to control conditions (no light filtering), black sheet covering inhibited flower bud induction by 87.5%, red sheet covering by 46.6% and blue sheet covering by 34%, and the respective inhibiting effects on number of flowers in bloom were essentially 100%, ~81% and ~44%. C. peruvianus is a unique example of a terrestrial plant that exhibits a circadian flowering rhythm (peak ~00:00 h) "gated" by 24 h, lunar 29.5-day (bright light of full moon) and annual 365.25-day (prolonged summertime day length) environmental photoperiod cycles.

Protective effect of resveratrol against lipopolysaccharide-induced oxidative stress in rat brain.

PRIMARY OBJECTIVE: To study the protective effect of resveratrol on endotoxemia-induced neurotoxicity. METHODS: Rats were pre-treated during 7 days with 20 mg kg(-1) body weight (b.w.) resveratrol and challenged with a single dose of lipopolysaccharide (LPS: 8 mg kg(-1) b.w.) for 24 hours. Brains were harvested to determine LPS-induced lipoperoxidation level, antioxidant enzyme activities, nitric monoxide (NO) and iron distribution as well as the impact of resveratrol on these parameters. RESULTS: Resveratrol counteracted LPS-induced brain malondialdehyde (MDA) level and antioxidant enzyme activities depletion as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Resveratrol also reversed LPS-induced brain and plasma NO elevation as well as iron sequestration from plasma to brain compartment. CONCLUSION: The data suggest that resveratrol is capable of alleviating LPS-induced neurotoxicity by a mechanism that may involve iron shuttling proteins.

Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxidant during day-time and antioxidant at night.

We investigated the dosing-time dependency of acute resveratrol administration on lipoperoxidation level found in the heart, liver and kidney of male rats synchronized with a 12-h dark-light cycle. Resveratrol was administered by the i.p. route at the middle of the dark (6 h after dark onset, HADO) or light span (18 HADO) and thiobarbituric acid reactive species (TBARS) measured 4 h later at 10 and 22 HADO, respectively. Basal TBARS levels in the three organs were higher during the night span when compared to day span. Resveratrol effect on tissues TBARS was also dosing-time dependent. When administered during the dark phase, resveratrol decreased TBARS levels whereas at the light span, the polyphenol increased TBARS in the three organs. Resveratrol behaved as an antioxidant during the dark span and as a pro-oxidant during the light span. These data suggested a day/night rhythm in basal lipoperoxidation and in resveratrol antioxidant effect.

Age-related changes in the activity of cerebral rhodanese in mice during the first four months of life.

Rhodanese (thiosulfate sulfurtransferase) is a ubiquitous enzyme that accelerates the transformation of cyanide into the very less toxic thiocyante. Influence of cerebral rhodanese level on cyanide toxicity has already been shown in mice. However, age-related changes in rhodanese activity have not been previously examined. The aim of the experiments was to investigate age-related changes of cerebral rhodanese activity in male and female mice maintained from birth to age 16 weeks under 12:12 light:dark (LD) cycle conditions. The rhythm of enzyme activity was quantified by Cosinor test programme in 2-, 4-, 8-, 12-, and 16-week-old mice. Significant ultradian (tau =1 2h) rhythms were validated both by ANOVA (P < 0.05) and Cosinor analyses (P < or = 0.01) in 2- and 4-week-old mice. However, in addition to the ultradian rhythm, a significant (P < or = 0.01) prominent circadian (tau = 24h) rhythm, whose peak time located at approximately 9 Hours After Light Onset (HALO), was detected in 4-week-old females. In 8-, 12-, and 16-week-old mice, the Cosinor validated significant (P < or = 0.0001) circadian rhythms in both genders. The circadian peak time initially located at approximately 5 HALO in 8-week-old mice, moved to approximately 9 HALO and then to be stabilized at approximately 17 HALO in 12- and 16-week-old mice, respectively. Furthermore, the ultradian components were detected in 8- and 12-week-old females. On the other hand, at age 16 weeks, no significant ultradian rhythm was detected in males or in females. The enzyme activity was greater in females compared to males during the first 8 postnatal weeks. Two-way ANOVA revealed a significant (P < 0.02) interaction between circadian time and gender in 4-, 8-, 12-, and 16-week-old mice, suggesting the influence of gender on time-related changes in rhodanese activity. However, though ANOVA validated significant changes related to both sampling-time and gender, no interaction was detected between the two factors in 2-week-old mice, illustrating the gender-related difference in enzyme activity was greater. Moreover, the obtained results showed that rhodanese activity significantly increased with age during the postnatal development (PND). However, this increase would be limited by age in old mice as early as 12 weeks after birth. The data also showed a 12h phase-shift of the circadian rhodanese peak time during PND, suggesting that the rhythm stabilization is age dependent. The main findings of this study indicated that the increased sensitivity to cyanide, generally reported in old mice, may be due in part to a decrease in the activity of brain rhodanese.

Seasonal modulation of the 8-and 24-hour rhythms of ondansetron tolerance in mice.

Ondansetron (Zophren((R))) is a serotonin 5HT(3)-receptor antagonist used primarily to control nausea and vomiting caused by cytotoxic chemo-and radio-therapy. Tolerance to this drug shows both 24 and 8 h periodicities. In this framework, this study aimed to determine whether these ondansetron tolerance rhythms are modulated by season. The chronotoxic effect of a fixed dose (3.5 mg/kg, i.p.) of the drug was investigated with reference to both time of the day and year dependencies. Season-related studies were performed on 560 male Swiss mice, 10 to 12 wks old, synchronized with L:D=12:12 for three weeks. During a 1 yr span (2005), four 24 h studies were performed with a single dosing time at 1, 7, 13, and 19 hours after light onset (HALO), respectively. Tolerance was assessed daily during a 40-day span after acute ondansetron treatment. Both chi(2) test and cosinor methods were used to analyze the time series data. Statistically significant dosing time-dependent changes were validated in both yearly and daily time scales. The 24 h mean survival rate peaked in spring (92%) compared to fall (72%), the 20% difference being statistically significant (chi(2) test with p<0.05 and cosinor with p<0.0001 for seasonal rhythm detection and with a peak time, Ø,=April 3+/-6.6 days). A 24 h rhythm was also detected in each of the seasonal time points. However, the curve pattern was monophasic in fall as well as spring. In fall, a large amplitude (A) circadian rhythm was detected that peaked at 19 HALO, while in the spring, a small circadian rhythm was detected that peaked at 1 HALO. The curve pattern was biphasic in summer (with large A) and in winter (with a small A). The existence of two peaks of equal magnitude in winter (100% survival rate) and in summer (100% and 90%) suggests the presence of both circadian and ultradian rhythms rather than an ultradian component of the 24 h period. The seasonal modulation of ondansetron circadian chronotolerance seems to involve several rhythm parameters: season-related changes in the 24 h mean (M), amplitude (A), acrophase location (Ø), as well as bimodal curve patterns including the coexistence of rhythms with respectively 24 and 8 h periods in winter and summer. In conclusion, tolerance to ondansetron varies not only according to the 24 and 8 h periods but also according to seasons, which suggests the complexity of ondansetron toxicity rhythms. Seasonal modulation of ondansetron tolerance may also influence the strategies of chemo-and chrono-therapy, and it is therefore necessary to take it into account in clinical drug-delivery protocols to minimize side effects of cytotoxic anticancer and antiemetic agents.

Malondialdehyde content and circadian variations in brain, kidney, liver, and plasma of mice.

In aerobic organisms, the use of oxygen (O(2)) to produce energy is associated with the production of Reactive Oxygen Species (ROS), which reacts with biological molecules to produce oxidized metabolites such as malondialdehyde (MDA). This experiment focused on male Swiss mice 12 weeks of age synchronized for 3 weeks by the 12 h light (rest)/12 h dark (activity) span. Different and comparable groups of animals (n=10) were sacrificed at six different circadian stages: 1, 5, 9, 13, 17, and 21 h after light onset (HALO). The 24 h mean MDA level varied among organs of mice in non-stress conditions and was comparable in brain and liver but lower than in kidney. As the MDA 24 h status constitutes only a part of ROS damages in sites differing by their oxygen use, lipid composition, and detoxification capacity, the temporal patterns of their MDA content were comparatively studied in relationship to the animal rest-activity cycle. The results revealed significant circadian rhythms with the peak time located during the rest span (approximately =5 HALO) for both brain and liver, but during the activity span for the kidney ( approximately =21 HALO) and plasma (approximately =13 HALO). This chronobiological study showed that under physiological conditions, lipid peroxidation depends on several factors. The MDA peak/trough might be used as a tool to detect moments of high/low sensitivity of tissues to ROS attack in rodents.

Catalase activity and rhythmic patterns in mouse brain, kidney and liver.

To protect tissues from damaging effects of reactive oxygen species (ROS), organisms possess enzymatic and non-enzymatic antioxidant systems. Cytosolic-enzyme catalase (CAT) is a component of the antioxidant defence system that reduces hydrogen peroxide (H(2)O(2)) to water (H(2)O). The aim of this study was to assess the variation of antioxidant enzyme CAT activity in brain, kidney and liver of adult male mice according to tissue-specific and temporal patterns within a 24-h period (12:12 L/D). The CAT activity was assayed at 4-h intervals. The Cosinor test programme was used to detect and confirm the best corresponding rhythm. In liver, the circadian rhythm of CAT was associated with ultradian components. The prominent circadian rhythm (with a period tau=24 h) showed a peak located at the middle of the dark phase, more precisely congruent with 17 HALO (Hours After Light Onset). In kidney, only a circadian rhythm of CAT was validated with a peak time located at congruent with 17 HALO. However, in brain, the time pattern of CAT activity showed two peak times at congruent with 1 and congruent with 17 HALO, illustrating the existence of an ultradian rhythm (with a period tau=12 h). The results showed significant organ differences with the highest activity in liver, compared with kidney (-89%) and brain (-98%). This might be related to several factors such as their respective physiological function, the risk of exposure to oxidative damage and the balance between synthesis and degradation of proteins during "normal metabolism". Moreover, CAT activity revealed differences in time-related changes across a 24-h period that were more obvious in peak levels between the three tissues.

Circadian and ultradian (12 h) rhythms of hepatic thiosulfate sulfurtransferase (rhodanese) activity in mice during the first two months of life.

Thiosulfate sulfurtransferase (TST) is an important 'enzyme of protection,' that accelerates the detoxification of cyanide, converting it into thiocyanate. The TST physiological rhythm was investigated at wks 2, 4, and 8 of post-natal development (PND) in the mouse. The results revealed a statistically significant gender-related difference, with the highest activity in females, at all the documented PND stages. In the second week of PND (pre-weaning time), the circadian rhythm of the enzyme activity was associated with ultradian components. The prominent circadian rhythm (tau=24 h) peaked at the beginning of the light span, more precisely approximately 3 HALO (Hours After Light Onset). A week after weaning (wk 4 of PND), an impairment of the rhythm, with the peak shifted toward the second half of photophase, was recorded. Four to 6 wks later, about wk 8 of PND, the circadian rhythm pattern was stabilized, with its peak then located at the beginning of the dark span (13 HALO). The obtained results showed a 12 h phase-shift of the circadian TST peak time during PND, suggesting that the rhythm stabilization is age-dependent.

Circadian rhythms in toxic effects of the serotonin antagonist ondansetron in mice.

The aim of the study was to learn whether the lethal and the motor incoordination (ataxia) side effect of ondansetron (Zophren) administration is dosing-time dependent. Ondansetron is a serotonin 5-HT3 receptor antagonist used primarily to control nausea and vomiting arising from cytotoxic chemo- and radiotherapy. A total of 210 male Swiss mice 10 to 12 weeks of age were synchronized for 3 weeks by 12 h light (rest span)/12 h dark (activity span). Different doses of ondansetron were injected intraperitoneally (i.p.) at fixed times during the day to determine both the sublethal (TD50) and lethal (LD50) doses, which were, respectively, 3.7 +/- 0.6 mg/kg and 4.6 +/- 0.5 mg/kg. In the chronotoxicologic study a single dose of ondansetron (3.5 mg/kg, i.p.) was administered to different and comparable groups of animals at four different circadian stages [1, 7, 13, and 19 h after light onset (HALO)]. The lethal toxicity was statistically significantly dosing time-dependent (chi2 = 21.51, p < 0.0001). Drug dosing at 1 HALO resulted in 100% survival rate whereas drug dosing at 19 HALO was only one-half that (52%). Similarly, lowest and highest ataxia occurred when ondansetron was injected at 1 and 19 HALO, respectively (chi2 = 22.24, p < 0.0001). Effects on rectal temperature were also dosing-time related (Cosinor analysis, p < 0.0001). The characteristics of the waveform describing the temporal patterns differed between the studied variables, e.g., lethal toxicity and survival rate showing two peaks and rectal temperature showing one peak in the 24 h time series waveform pattern. Cosinor analysis also revealed a statistically significant ultradian (tau = 8 h) rhythmic component in the considered variables. Differences in curve patterns in toxicity elicited by ondansetron on a per end point basis are hypothesized to represent the phase relations between the identified 24 h and 8 h periodicities.