Diphenyl diselenide protects against metabolic disorders induced by acephate acute exposure in rats.

The present study investigated the effect of diphenyl diselenide [(PhSe)2 ] on metabolic disorders induced by acephate acute exposure in rats. We also investigated a possible mechanism of action of (PhSe)2 against hyperglycemia induced by acephate. (PhSe)2 was administered to rats at a dose of 10 or 30 mg/kg by oral gavage (p.o.) 1 hour prior to acephate administration (140 mg/kg; p.o.). Glucose and corticosterone levels as well as the lipid status were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels as well as tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was assayed. Acephate induced an increase in glucose and corticosterone levels as well as in TAT and G6Pase activities. AChE activity was inhibited by acephate. Triglyceride (TG) levels and the cardiovascular risk factor TG/high-density lipoprotein-cholesterol (HDL) were increased by acephate. (PhSe)2 was effective against the metabolic disorders induced by acephate acute exposure in rats.

Chlorpyrifos acute exposure induces hyperglycemia and hyperlipidemia in rats.

In this study we evaluated the hyperglycemic and hyperlipidemic effects of chlorpyrifos (CPF) after an acute exposure in rats. The mechanisms involved in hyperglycemia induced by CPF were studied. A single dose of CPF (50 mg kg(-1), subcutaneous, s.c.) was administered to overnight-fasted rats. Glucose and corticosterone levels, lipid status and paraoxonase (PON1) activity were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels, tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was also determined. CPF caused an increase in glucose and glycogen levels as well as in TAT and G6Pase activities. The CPF exposure caused an increase in corticosterone levels, an inhibition of AChE activity and a reduction of PON1 activity. Regarding the lipid status, CPF induced an increase in triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels and a decrease in high-density lipoprotein (HDL) levels associated with an increase of cardiovascular risk factors and the atherogenic index. The present study demonstrated that a single CPF administration caused hyperglycemia and hyperlipidemia in rats. The activation of the gluconeogenesis pathway, probably elicited by hypercorticosteronemia, is involved in the hyperglycemic effect of CPF in rats.

Diphenyl diselenide attenuates hepatic and hematologic toxicity induced by chlorpyrifos acute exposure in rats.

PURPOSE: In this study, we investigated the effect of diphenyl diselenide [(PhSe)(2)] on chlorpyrifos (CPF)-induced hepatic and hematologic toxicity in rats. METHODS: Rats were pre-treated with (PhSe)(2) (5 mg/kg) via the oral route (oral gavage) once a day for 7 days. On the eighth and ninth days, rats were treated with (PhSe)(2) (5 mg/kg) 30 min prior to CPF (50 mg/kg, by subcutaneous route). The aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities were determined in plasma of rats. Lipid peroxidation, protein carbonyl, and non-protein thiol levels as well as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and gluthatione S-transferase activities were determined in livers of rats. Hematological parameters were also determined. RESULTS: The results showed that CPF caused hepatic oxidative damage, as demonstrated by an increase in lipid peroxidation and protein carbonyl levels which was associated with a decrease in antioxidant defenses. CPF exposure caused a reduction in the leukocyte, indicating hematologic toxicity. (PhSe)(2) was effective in attenuating these toxic effects caused by CPF exposure in rats. CONCLUSIONS: The results indicated that (PhSe)(2) was effective in protecting the hepatic and hematologic toxicity induced by acute CPF exposure in rats.

2-phenylethynyl-butyltellurium improves memory in mice.

The present study was conducted to evaluate the effect of 2-phenylethynyl-butyltellurium (PEBT), an organotellurium compound, at doses of 5 and 10 mg/kg on memory, employing the step-down inhibitory avoidance task in mice. Moreover, the involvement of glutamate uptake and release in cerebral cortex and hippocampus of mice was investigated. A single oral administration (p.o.) of PEBT at the dose of 10 mg/kg 1h before training (acquisition), immediately after training (consolidation) or 1 h before the test session (retrieval) of the step-down inhibitory avoidance task increased the step-through latency time in comparison to the control mice. In the open-field test, no significant differences in the number of crossings and rearings were observed among groups. The [(3)H]glutamate uptake by cerebral cortex and hippocampal slices of mice was significantly inhibited after 1h of treatment with PEBT. After 24h of PEBT exposure, only the hippocampal [(3)H]glutamate uptake was inhibited. The [(3)H]glutamate release by cerebral cortex and hippocampal synaptosomes of mice was not altered. These results suggest that PEBT improved memory stages (acquisition, consolidation and retrieval) in the step-down inhibitory avoidance task in mice. The improvement of memory by PEBT seems most likely to be mediated through an interaction with the amino acid transporters of the glutamatergic system.

Repeated malathion exposure induces behavioral impairment and AChE activity inhibition in brains of rat pups.

The present study evaluated if repeated malathion administration would cause behavioral impairment in rat pups. Na+K+ ATPase and acetylcholinesterase (AChE) activities were investigated in brains of rat pups. Malathion was administered (100 or 200 mg/kg) orally (p.o.), once a day for four consecutive days. Rat pups were submitted to behavioral tests on the 5th day, 24 h after the last malathion administration. Malathion at the dose of 200 mg/kg caused a significant increase in the negative geotaxis latency and a decrease in the rotarod latency of rat pups. Rat pups exposed to malathion at both doses showed a significant decrease in the forelimb support latency and an inhibition of brain AChE activity. Repeated exposure of rat pups to malathion caused a decrease in motor coordination, vestibular function and muscular strength/coordination. The brain activity of AChE is involved in the behavioral alterations caused by malathion in rat pups.

Antinociceptive effect of butyl (2-phenylethynyl) selenide on formalin test in mice: Evidences for the involvement of serotonergic and adenosinergic systems.

The present study investigated the effect of per oral (p.o.) administration of butyl (2-phenylethynyl) selenide (1-50mg/kg) on formalin-induced nociception in mice. The involvement of serotonergic, adenosinergic, muscarinic cholinergic and opioid mechanisms in the antinociceptive effect was also investigated. Butyl (2-phenylethynyl) selenide inhibited both neurogenic (at doses equal or higher than 10mg/kg) and inflammatory (at doses equal or higher than 25mg/kg) phases of the nociception caused by intraplantar (i.pl.) injection of 2.5% formalin solution (20 microl), with ID(50) values of 36.7 (29.28-46.0) and 20.37 (15.74-26.36) mg/kg, respectively. This compound reduced the formalin-induced paw oedema formation (55 + or - 4%) at doses equal or higher than 25mg/kg. The antinociceptive effect of compound (25mg/kg, p.o.) was reversed by ondansetron (0.5mg/kg, a 5-HT(3) receptor antagonist) and caffeine (3mg/kg, a nonselective adenosine receptor antagonist), but not by atropine (0.1mg/kg, a non selective muscarinic antagonist), WAY100635 (0.1mg/kg, a selective 5-HT(1A) receptor antagonist), ritanserin (1mg/kg, a 5-HT(2) receptor antagonist) and naloxone (1mg/kg, a non selective opioid receptor antagonist). These results indicate that butyl (2-phenylethynyl) selenide produced antinociception in the formalin test through mechanisms that involve an interaction with serotonergic (5-HT(3)) and adenosinergic systems.

Antioxidant effect of alkynylselenoalcohol compounds on liver and brain of rats in vitro.

Alkynylselenoalcohol compounds were screened for in vitro antioxidant activity. Alkynylselenoalcohols (2a-2d) were tested against lipid and protein oxidation induced by sodium nitroprusside (SNP) in rat brain and liver. The influence of molecular structural modifications of alkynylselenoalcohols in their antioxidant activity was investigated. The 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and the interaction of alkynylselenoalcohols with iron were carried out. The results revealed that the antioxidant activity depends on their chemical structures. Compounds 2e (without hydroxyl group) and 3a (with a tellurium atom) presented better antioxidant profiles than 2b (with a hydroxyl group and selenium atom) against lipid and protein oxidation. Compound 1a (with a butyl group) did not modify the effect of compound 2a (with a phenyl group) on lipid oxidation. Compounds 2e and 3a showed DPPH radical-scavenging activity. Compounds 2b, 2c and 3a inhibited isocitrate-mediated oxidation of Fe(2+). Alkynylselenoalcohols demonstrated antioxidant effects and the modifications in the molecular structure of compound 2b improved its antioxidant potency.