Effects of oral phytoextract intake on phenolic concentration and redox homeostasis in murine encephalic regions.

Vegetable infusions (VI) are one of the main phenolic sources for humans. They may act as antioxidants in the central nervous system, but data about their effect are insufficient. The main objective of the study was to determinate the effects of oral VI of Argentinean plants on phenolic concentration and redox homeostasis in different murine encephalic regions. Redox changes (peroxides -HP-, anion superoxide -SO- and γ-glutamyltranspeptidase activity) and tissue phenolics were assessed in Balb/c mice of both sexes treated with the following VI extracts: Lantana grisebachii Seckt. var. grisebachii (Verbenaceae) (LG), Aspidosperma quebracho-blanco Schltdl. (Apocynaceae) (AQB), and Ilex paraguariensis A. St.-Hil. (Aquifoliaceae) (IP). Brain (telencephalon and diencephalon), midbrain, brainstem, and cerebellum were studied (analysis of variance, P < 0.05). A redox homeostasis depending on an appropriate phenolic balance was detected after marker analysis. Under situations without exogenous challenges, the excessive or deficient levels were deleterious on each region. This finding was confirmed independently of the utilized phytoextracts. LG and AQB caused such phenolic imbalance and triggered oxidative stress. IP group showed region-specific differential redox effects. Overall, the last extract exhibited the best redox profile when the complete encephalon was analyzed. Since this plant has sanitary impact due to its high human intake, new studies about it are warranted.

In vivo redox effects of Aspidosperma quebracho-blanco Schltdl., Lantana grisebachii Stuck and Ilex paraguariensis A. St.-Hil. on blood, thymus and spleen of mice.

Argentinian native plants Aspidosperma quebracho-blanco, Lantana grisebachii and Ilex paraguariensis are known to have antiinflammatory and antioxidant properties. We demonstrated it in vivo by the redox changes in murine hemolymphatic tissues after infusive extract intake of these plants as revealed in organic trophism, tissue phenolics, hydroperoxides, superoxide, nitrites and gamma-glutamyltranspeptidase in thymus, blood and spleen. A. quebracho-blanco reduced hydroperoxidation in blood and spleen of both sexes, with gamma-glutamyltranspeptidase negativization in lymphatic organs and thymic nitrosative up-regulation. Males have shown increased phenolic content in blood after treatment. L. grisebachii and I. paraguariensis treatment exhibited incomplete antioxidation and oxidative induction in the studied tissues. Different results according to sex were found in redox response to phenolics and their kinetics, with males showing antioxidant effects, whereas females showed oxidative susceptibility. A. quebracho-blanco exhibited protection of murine tissues against oxidation in both sexes and modulation of their trophism, supporting its therapeutic uses in inflammatory diseases. Also, gender had significant influence in phenolic biodistribution and redox response.

Nutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents: risk for UTT in children exposed to melamine-contaminated milk formulas.

Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.

Pharmacoepidemiological approach to the predisposing factors for highly active antiretroviral therapy failure in an HIV-positive cohort from Cordoba City (Argentina) 1995-2005.

Highly active antiretroviral therapy (HAART) restores immunity, avoids resistance and delays disease progression. Nonetheless, adverse medicament reactions (AMRs) and therapeutic failure (TF) are still deleterious events. Consequently, their predisposing factors should be evaluated. Data from 181 men and 28 women of an Argentinean cohort (1995-2005) were collected and analysed by logistic regression, studying 63 schemes (15 active principles). The AMRs were the main cause of scheme change, followed by TF and medicament simplification, without influence of age and sex. Twenty-nine schemes exhibited TF at least once. Compared with zidovudine-lamivudine-nevirapine (success: >75%), the following schemes fail more frequently (P < 0.01): pre-HAART (8-fold), indinavir-containing ones (30-fold) and retrotranscriptase inhibitors with > or =3 protease inhibitors (11-fold). Inadequate patient adherence preceded failure (>95%), but not successful treatments, with a strong AMR-TF association (P < 0.005). Although some schemes had inherently increased TF, low adherence, drug toxicity and TF were critically interrelated, interfering with HAART goals.

Antioxidant activity of different extracts of Argentinian medicinal plants against arsenic-induced toxicity in renal cells.

Chronic toxicity of arsenic resulting from drinking water is a health problem encountered in humans, especially in South America and Asia, where a correlation between oxidative stress, tumor promotion, and arsenic exposure has been observed. Differential solvent extraction (petroleum ether (PE); dichloromethane (DCM); methanol (OL) and water (W)) was performed to compare the protective (antioxidant) activity of five Argentinian medicinal plants on arsenite-induced oxidative stress in Vero cells, assayed by hydroperoxide measurement. The results were analyzed using ANOVA followed by the LSD Fisher test. The data showed that arsenite was a pro-oxidant agent which acts in a time-dose-dependent manner. Extracts from Eupatorium buniifolium (PE), Lantana grisebachii (PE, W), Mandevilla pentlandiana (PE, W), and Sebastiania commersoniana (DCM, OL, W) prevented the formation of both aqueous and lipid hydroperoxides, but Heterothalamus alienus only impeded lipid ones. Therefore, antioxidant extracts are potentially beneficial and may have a protective activity against arsenite-induced renal injury. Among these, the aqueous extract of L. grisebachii may represent the most suitable preparation for humans since the traditional usage of this plant in popular medicine is through consumption of tea.

Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells.

Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.

[Analysis of tissue bioavailability of total polyphenols by Folin Ciocalteu and Fast Blue BB techniques in organs of BALB/C/c mice]. / Análisis de la biodisponibilidad tisular de polifenoles totales mediante las técnicas de Folin Ciocalteu y Fast Blue BB en órganos de ratones BALB/C.

Biomedical potential of polyphenols lies in their ability to modulate redox balance and the mechanisms involved in the development of chronic noncommunicable diseases. OBJECTIVE: The aim of this study was to determine the concentration of total polyphenols in different murine organs by assaying analytical techniques of Folin Ciocalteu (FC) and Fast Blue BB (FBBB). METHOD: Balb/c female mice (n≥3) received for 15 days 100 mg/kg/d of extract of Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQB) or Ilex paraguariensis (IP) and control group (treated with water without extract). Polyphenolic concentrations were measured in telencephalon, diencephalon, midbrain, brainstem, cerebellum, spleen, thymus and cardiopulmonary tissue by FC and FBBB methods. Results were compared by ANOVA followed by Tukey test (p<0.05). RESULTS: FBBB method reported higher detections than FC (4.5 fold in telencephalon, 8.4 in midbrain, 5 in brainstem, 7.2 in spleen, 68.5 in thymus and 4 in cardiopulmonary tissue). Regarding the treatments, the group that received AQB showed to have increased polyphenolic bioavailability in brainstem (p<0.02). With FBBB, a decrease on thymic polyphenol content after treatment with IP was detected (p<0.005). In cerebellum of the groups treated with IP and telencephalon of the control group showed significant differences when these were analyzed with FC (p<0.05, p<0.0035 respectively). CONCLUSIONS: FBBB method showed higher estimations of polyphenolic bioavailability than FC, and this could be related to higher specificity of the technique to react with phenolic compounds.

Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies.

Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.