Methyl and Ethylmercury elicit oxidative stress and unbalance the antioxidant system in Saccharomyces cerevisiae.

Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants.

Selenium and mercury levels in rat liver slices co-treated with diphenyl diselenide and methylmercury.

Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)2 (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)2 and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)2 and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)2 could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.

Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 µmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 µmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 µmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 µmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

Effect of Syzygium cumini and Bauhinia forficata aqueous-leaf extracts on oxidative and mitochondrial parameters in vitro.

Aqueous-leaf extract of Syzygium cumini and Bauhinia forficata are traditionally used in the treatment of diabetes and cancer, especially in South America, Africa, and Asia. In this study, we analyzed the effects of these extracts on oxidative and mitochondrial parameters in vitro, as well as their protective activities against toxic agents. Phytochemical screenings of the extracts were carried out by HPLC analysis. The in vitro antioxidant capacities were compared by DPPH radical scavenging and Fe(2+) chelating activities. Mitochondrial parameters observed were swelling, lipid peroxidation and dehydrogenase activity. The major chemical constituent of S. cumini was rutin. In B. forficata were predominant quercetin and gallic acid. S. cumini reduced DPPH radical more than B. forficata, and showed iron chelating activity at all tested concentrations, while B. forficata had not similar property. In mitochondria, high concentrations of B. forficata alone induced a decrease in mitochondrial dehydrogenase activity, but low concentrations of this extract prevented the effect induced by Fe(2+)+H2O2. This was also observed with high concentrations of S. cumini. Both extracts partially prevented the lipid peroxidation induced by Fe(2+)/citrate. S. cumini was effective against mitochondrial swelling induced by Ca(2+), while B. forficata alone induced swelling more than Ca(2+). This study suggests that leaf extract of S. cumini might represent a useful therapeutic for the treatment of diseases related with mitochondrial dysfunctions. On the other hand, the consumption of B. forficata should be avoided because mitochondrial damages were observed, and this possibly may pose risk to human health.

Effect of pioglitazone on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance.

AIM: To evaluate the effect of a thiazolidinedione, pioglitazone, on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 overweight or obese patients with both impaired fasting glucose and impaired glucose tolerance. Pharmacological intervention consisted of an oral morning administration of pioglitazone (30 mg) or a placebo with a similar presentation for 30 days. Before and after the intervention, glucose, creatinine, lipid profile and uric acid concentrations were measured. To evaluate insulin secretion (early, late and total phases) and insulin sensitivity, a hyperglycemic-hyperinsulinemic clamp was also performed. RESULTS: There were significant reductions (p=0.008) in fasting insulin concentration (121 versus 45 pmol/l), late (565 versus 307 pmol/l) and total insulin secretion (474 versus 254 pmol/l), as well as, in 2h postload glucose levels (9.7 versus 6.9 mmol/l, p=0.028), with an increment in insulin sensitivity after pioglitazone administration (7.5 versus 9.9). CONCLUSION: Pioglitazone administration during a period of 4 weeks decreased late and total insulin secretion phases, fasting insulin and 2h postload glucose levels, and improved insulin sensitivity in patients with both impaired fasting glucose and impaired glucose tolerance.

Effect of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy men.

AIM: The purpose of this study is to identify the effect of a low dose of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy young men. METHODS: An open clinical trial was carried out in eight healthy nonobese, young male volunteers. The study was divided in two phases. The first one evaluated metabolic changes, including insulin secretion and sensitivity due to acute administration of 30 ml of straight tequila. The second phase of the study evaluated metabolic effects due to the daily administration of 30 ml of tequila during 30 days. RESULTS: There were no significant metabolic changes after the single oral administration of 30 ml of straight tequila. After the administration of tequila during 30 days, a significant increase in homocysteine levels and a tendency to increase the glucose concentration and to decrease the insulin sensitivity were found. CONCLUSION: Detrimental metabolic changes were observed with the daily administration of 30 ml of tequila during 30 days.

Effect of celecoxib, a cyclooxygenase-2-specific inhibitor, on insulin sensitivity, C-reactive protein, homocysteine, and metabolic profile in overweight or obese subjects.

BACKGROUND: The aim of this study was to assess the effect of celecoxib, a cyclooxygenase- 2-specific inhibitor, on insulin sensitivity, C-reactive protein, homocysteine, and metabolic profile in overweight or obese subjects. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out on 12 overweight or obese (body mass index, 25-35 kg/m(2)) male volunteers. Six subjects received celecoxib 200 mg orally in the morning for a period of 4 weeks. Six other individuals took a placebo for the same period of time, as the control group. Before and after the 4-week study period, insulin sensitivity, C-reactive protein, homocysteine levels, and metabolic profile were estimated. To assess insulin sensitivity, the euglycemic-hyperinsulinemic clamp technique was performed. RESULTS: There were no significant differences in the basal measurements between both groups. C-reactive protein, homocysteine, and metabolic profile were not modified by the pharmacologic intervention with placebo or celecoxib. The insulin sensitivity after celecoxib was significantly higher compared with the basal estimation (3.8 +/- 1.2 vs. 2.8 +/- 1.2 mg/kg/min; p = 0.028). The placebo did not modify the insulin sensitivity. CONCLUSIONS: The specific inhibition of the cyclooxygenase-2 by celecoxib increased the insulin sensitivity in overweight or obese subjects, without modification in C-reactive protein, homocysteine levels, and metabolic profile.

Reactividad de sueros de pacientes chagásicos crónicos con extractos de aislamientos mexicanos de Trypanosoma cruzi / Reactivity of sera from Chagas patients to extracts of mexican Trypanosoma cruzi isolates

An antigenic extract prepared from four different Mexican isolates of Trypanosoma cruzi cultured on BHI (three came from human cases-Agripina, Fidelfa and Ninoa, and other from triatoma-Cocula) were assayed with human sera. ELISA results always were consistent with clinical diagnosis. Sera from patients with a diagnosis of Chagas disease were reactive and non-chagasic sera were negative. Western blot of chagasic sera recognized antigens of molecular weight > 81 kd, 81 kd, 54 kd, 42 kd, and 26 kd. Sera with high OD in ELISA reacted with more peptide bands. The soluble extract antigens prepared from Mexican isolates of T. cruzi and from the Brazilian Y strain have an homogenous and similar reactivity.