Potentially adverse interactions between haloperidol and valerian.

This study was designed to determine whether the treatment with haloperidol (HP), valerian or both in association impairs the liver or kidney functions. Valerian alone did not affect oxidative stress parameters in the liver or kidney of rats. HP alone only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and dichlorofluorescein (DCFH) reactive species production was observed in the hepatic tissue. Superoxide dismutase (SOD) and Catalase (CAT) activities were not affected by the HP plus valerian treatment in the liver and kidney of rats. HP and valerian when administered independently did not affect the activity of hepatic and renal delta-aminolevulinate dehydratase (delta-ALA-D), however, these drugs administered concomitantly provoked an inhibition of hepatic delta-ALA-D activity. The delta-ALA-D reactivation index was higher in rats treated with HP plus valerian than other treated groups. These results strengthen the view that delta-ALA-D can be considered a marker for oxidative stress. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Our findings suggest adverse interactions between haloperidol and valerian.

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity.

The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic delta-ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies.

Dietary diphenyl diselenide reduces the STZ-induced toxicity.

Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluated whether dietary diphenyl diselenide, a simple synthetic organoselenium compound with antioxidant properties, reduces the streptozotocin (STZ)-induced toxicity. STZ-induced diabetic rats were fed with either standard and diphenyl diselenide (10 ppm) supplemented diets. In experimental trials, dietary diphenyl diselenide significantly decreased mortality rate (p<0.05) induced by STZ treatment. No correlation between this effect and glycemic levels were found. Diphenyl diselenide intake also promoted an increase in vitamin C, -SH levels (liver, kidney and blood) and in catalase (liver and kidney) activity, which were decreased in STZ-treated rats. In enzyme assays, diphenyl diselenide supplementation caused a significant improvement in platelets NTPDase and 5'-nucleotidase activities in STZ-induced diabetic rats when compared to the control and diabetic groups (p<0.05). Nevertheless, this supplementation did not modify the inhibition induced by STZ in delta-ALA-D activity. Our findings suggest that diphenyl diselenide compound showed beneficial effects against the development of diabetes by exhibiting antioxidant properties.

Organochalcogens effects on delta-aminolevulinate dehydratase activity from human erythrocytic cells in vitro.

Organochalcogens are important intermediates and useful reagents in organic synthesis, which can increase human exposure risk to these chemicals in the workplace. As well, there are a number of reported cases of acute toxicity following organochalcogen ingestion of vitamins and dietary supplements. Since, the erythrocytic delta-ALA-D activity could be an important indicator of toxicity this report investigated the organochalcogens effects on blood delta-ALA-D in vitro. To investigate a possible involvement of cysteinyl groups in the inhibitory actions of diphenyl diselenide, diphenyl ditelluride and Ebselen (4-100 micro M), the effects of thiol reducing agents (0-3 mM) or zinc chloride (0-2 mM) were examined. Diphenyl ditelluride, diphenyl diselenide and Ebselen inhibited in a concentration-dependent manner delta-ALA-D activity from human erythrocytes. Ebselen was lesser delta-ALA-D inhibitor than (PhSe)(2) and (PhTe)(2), whereas the diorganoyldichalcogenides displayed similar inhibitory potency towards delta-ALA-D. Dithiothreitol, a hydrophobic SH-reducing agent, was able to reactivate and to protect inhibited delta-ALA-D. The pre-incubation of blood with the inhibitors changed considerably the reversing potency of thiols. From these findings we suggest that organochalcogens inactivate in vitro human erythrocyte delta-ALA-D by an interaction with the sulfhydryl group essential of the enzyme activity.

Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice.

Sodium selenite (Na2SeO3) is the selenium form used in the composition of dietary supplements, and diphenyl diselenide (PhSe)2 is an important intermediate in organic synthesis, which increases the risk of human exposure to this chemical in the workplace. These compounds have been reported to inhibit the cerebral and hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that ascorbic acid can reverse some alterations caused by in vivo selenium exposure, but not ALA-D inhibition. The effect of Na2SeO3 or (PhSe)2 and ascorbic acid on selenium distribution, total non-protein thiol, ascorbic acid content (liver and brain) and haemoglobin was also examined. Mice were exposed to 250 micromol/kg (PhSe)2, or 18.75 micromol/kg Na2SeO3 subcutaneously, and to ascorbic acid, twice a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated with (PhSe)2 was inhibited about 58% and similar results were observed in the animals that received ascorbic acid supplementation (P<0.01, for (PhSe)2-treated and (PhSe)2+ascorbic acid-treated mice). The haemoglobin content decreased after treatment with (PhSe)2 (P<0.01). However, the haemoglobin content of the (PhSe)2+ascorbic acid group was significantly higher than in the (PhSe)2-treated mice (P<0.05), and similar to control (P>0.10). Ascorbic acid treatment decreased significantly the hepatic and cerebral deposition of Se in (PhSe)2-exposed mice (P<0.01). Hepatic non-protein thiol content was not changed by treatment with (PhSe)2, ascorbic acid or (PhSe)2+ascorbic acid. Hepatic content of ascorbic acid was twice that in mice that received (PhSe)2, independent of ascorbic acid treatment (P<0.001). The results of this study suggest that vitamin C may have a protective role in organodiselenide intoxication.