Guaraná (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study.

BACKGROUND: Previous experimental investigations have suggested that guaraná (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guaraná on LDL and serum oxidation. METHODS: The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guaraná (GI) or never ingested guaraná (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guaraná in their diets. The LDL samples were exposed to 5 different guaraná concentrations (0.05, 0.1, 0.5, 1, and 5 µg/mL). RESULTS: GI subjects demonstrated lower LDL oxidation than did NG subjects (reduction of 27%, p < 0.0014), independent of other variables. In the GI group the total polyphenols was positively associated with LDL levels. Also, guaraná demonstrated a high antioxidant activity in vitro, mainly at concentrations of 1 and 5 µg/mL, demonstrated by suppression of CDs and TBARS productions, tryptophan destruction and high TRAP activity. CONCLUSIONS: Guaraná, similar to other foods rich in caffeine and catechins such as green tea, has some effect on LDL oxidation that could partially explain the protective effects of this food in cardiometabolic diseases.

Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats.

The pathology of a gastric ulcer is complex and multifactorial. Gastric ulcers affect many people around the world and its development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. In this study, we evaluated the ethanolic extract of Rosmarinus officinalis L. (eeRo); this plant, more commonly known as rosemary, has attracted the interest of the scientific community due to its numerous pharmacological properties and their potential therapeutic applications. Here, we tested the preventive effects of eeRo against gastric ulcer induced by 70% ethanol in male Wistar rats. In addition, we aimed to clarify the mechanism involved in the preventive action of the eeRo in gastric ulcers. Based on the analysis of markers of oxidative damage and enzymatic antioxidant defense systems, the measurement of nitrite and nitrate levels and the assessment of the inflammatory response, the eeRo exhibited significant antioxidant, vasodilator and antiinflammatory properties.

Effect of repeated restraint stress and clomipramine on Na+/K+-ATPase activity and behavior in rats.

Activation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) and the release of glucocorticoids are fundamental for the adaptive response and immediate survival of an organism in reaction to acute stimuli. However, high levels of glucocorticoids in the brain may produce neuronal injury and a decrease of Na(+)/K(+)-ATPase activity, with effects on neurotransmitter signaling, neural activity, as well as the whole animal behavior. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and LHPA axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. The purpose of the present study was to compare the effect of repeated restraint stress and clomipramine treatment on Na(+)/K(+)-ATPase activity and on the behavior of male rats. Changes in the behavioral response were evaluated by measuring the memory, learning, anxiety, and exploratory responses. Our results showed that exposure to repeated restraint stress reduced levels of Na(+)/K(+)-ATPase in brain structures and changed short and long-term memory, learning, and exploratory response when compared to the control group. Exposure to clomipramine treatment increased anxiety levels and reduced Na(+)/K(+)-ATPase activity in the cerebral cortex as well as short term memory, learning, and exploratory response. In conclusion, the present results provide additional evidence concerning how repeated restraint stress and clomipramine chronically administered at higher dose levels affect the neural activity and behavior of male rats.

Thiosemicarbazone derivate protects from AAPH and Cu2+ -induced LDL oxidation.

AIMS: Several lines of evidence support the hypotheses that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Oxidative stress is one of the causes of the overproduction of reactive species that increase the formation of oxidized LDL. Thiosemicarbazones are compounds used in anticancer, antiviral and antifungal therapy; however, its redox activity has been controversial. Thus, we tested, in vitro, a possible antioxidant activity of a thiosemicarbazone derivate, the isatin-3-N(4)-benzilthiosemicarbazone (IBTC). MAIN METHODS: We measured the conjugated diene formation in serum and LDL as well as the loss of tryptophan fluorescence in LDL induced by two oxidant agents, 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH) and Cu(2+). Thiobarbituric acid reactive substances (TBARS) formation in LDL and in different rat tissues was also assessed. The toxicity of IBTC was measured using aortic slices viability assay. KEY FINDINGS: Our results show that IBTC significantly reduced the AAPH and Cu(2+)-induced formation of conjugated dienes, increased in a dose-dependent manner the lag phase and the t(1/2) of tryptophan fluorescence, and reduced the TBARS formation in LDL, plasma and rat tissues, showing no toxicity to aortic slices. SIGNIFICANCE: These results indicate that IBTC is a good antioxidant and a promising antiatherogenic agent for further studies in vivo.

Clomipramine treatment and repeated restraint stress alter parameters of oxidative stress in brain regions of male rats.

This study aimed to compare the effects of repeated restraint stress alone and the combination with clomipramine treatment on parameters of oxidative stress in cerebral cortex, striatum and hippocampus of male rats. Animals were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine. After 40 days of stress and 27 days of clomipramine treatment with 30 mg/kg, the repeated restraint stress alone reduced levels of Na(+), K(+)-ATPase in all tissues studied. The combination of repeated restraint stress and clomipramine increased the lipid peroxidation, free radicals and CAT activity as well as decreased levels of NP-SH in the tissues studied. However, Na(+), K(+)-ATPase level decreased in striatum and cerebral cortex and the SOD activity increased in hippocampus and striatum. Results indicated that clomipramine may have deleterious effects on the central nervous system especially when associated with repeated restraint stress and chronically administered in non therapeutic levels.

Diphenyl diselenide decreases serum levels of total cholesterol and tissue oxidative stress in cholesterol-fed rabbits.

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

Diphenyl diselenide, a simple glutathione peroxidase mimetic, inhibits human LDL oxidation in vitro.

Oxidative modification of low-density lipoprotein (LDL) represents an important factor in atherogenesis. In the present study, we have investigated the antioxidant capability of diphenyl diselenide (PhSe)(2), a simple organoseleno compound, against copper (Cu2+) and peroxyl radical-induced human LDL oxidation in vitro. In initial studies using human serum, (PhSe)(2) caused a dose-dependent inhibition of Cu(2+)-induced lipid peroxidation, which was correlated to thiol consumption. (PhSe)(2) increased lipid peroxidation lag phase and decreased lipid peroxidation rate in isolated human LDL, evaluated by measuring both conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) levels. Consistent with these observations, (PhSe)(2) showed a marked inhibitory effect on 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH)-induced oxidation of LDL or parinaric acid (PnA) incorporated into LDL. (PhSe)(2) also displayed a dose-dependent protective effect against Cu(2+)-induced lipid peroxidation in rat aortic slices. Interestingly, besides the antioxidant effects of (PhSe)(2) toward the lipid moieties of LDL, which was related to its thiol-peroxidase activity, protein moieties from human isolated LDL were also protected against Cu(2+)-induced oxidation. The results presented herein are the first to show that (i) (PhSe)(2) inhibits lipid peroxidation in human isolated LDL in vitro, (ii) this phenomenon is related to its thiol-peroxidase activity, and (iii) this chalcogen also prevents the oxidation of protein moieties of human LDL. Taken together, such data render (PhSe)(2) a promising molecule for pharmacological studies with respect to the atherogenic process.