Pre-cancerous changes in urothelial endocytic vesicle leakage, fatty acid composition, and As and associated element concentrations after arsenic exposure.

The urothelium covering the luminal surface of the urinary bladder has developed an efficient permeability barrier that protects it against the back-flow of toxins eliminated in the urine. The subapical endocytic vesicles containing the urinary bladder fluid phase are formed during the micturition cycle by endocytosis processes of the superficial cells. In normal conditions, the permeability barrier of the endocytic vesicles blocks the passage of the fluid phase to the cellular cytoplasm and the fluid is recycled to the bladder lumen. The aim of this work was to investigate the alteration of the endocytic vesicle membrane permeability barrier to toxins such as iAs (inorganic arsenic) administered in drinking water. By using an induced endocytosis model and the fluorescence requenching technique, it is shown that the exposure of rats to ingestion of water containing iAs not only induced pre-cancerous morphological changes, but allowed the differential leakage of an endocytosed fluorescent marker, HPTS, and its quencher, DPX, (hydroxypyrene-1,3,6-trisulfonic acid and p-xylene-bis-pyridinium bromide, respectively) out of the vesicular lumen. The leakage of the cationic DPX was almost complete, while the release of the anionic HPTS molecule was partial and higher in arsenic-treated-rats than in controls. Such membrane alteration would allow the toxins to elude the permeability barrier and to leak out of the endocytic vesicles, thus establishing a "bypass" to the permeability barrier. The retention of As in the urinary bladder, assessed by synchrotron radiation X-ray fluorescence spectrometry (SR-µXRF), was lower than the kidney accumulation of arsenic previously observed by our group and was accompanied by altered concentrations of K, Ca, Fe, Cu and Zn, all ions related to cellular metabolism. The results support the hypothesis that low amounts of endocytosed As can accumulate in the interior of the urothelial superficial cells and initiate the cytotoxic effects reflected in the morphological alterations observed.

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.

Medicinal plants from the "Sierra de Comechingones", Argentina.

Argentina is a country with both rich floral biodiversity and cultural diversity. Traditional herbal medicines are important in the health care of most people, and rely heavily on the use of indigenous plants. An ethnobotanical survey of the "Sierra de Comechingones" made over a 26-year period (1979-2005), indicated that 65 families and 149 different genuses were used in traditional medicines. The use of these medicines was observed to be widespread and prevalent over orthodox medicine. Medicinal native plants from this mountain range make up 31% of the total Argentina medicinal native flora. In addition, there are 15 endemic species that grow only in the region. The botanical name, popular uses, parts utilized, as well as the distribution of these medicinal plants from the "Sierra de Comechingones", Argentina, were summarized. Previous reports on phytochemical and biological activities in relation to cancer, antimicrobials and pesticides were also included.

Effect of the co-administration of phenobarbital, quercetin and mancozeb on nitrosomethylurea-induced pancreatic tumors in rats.

UNLABELLED: We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. CONCLUSION: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.