Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation.

Diphenyl diselenide prevents hepatic alterations induced by paraquat in rats.

This study aimed to investigate the beneficial effect of diphenyl diselenide (PhSe)2 on paraquat (PQ) induced alterations in rats liver. Adult male Wistar rats received (PhSe)2 at 10 mg kg(-1), by oral administration (p.o.), during five consecutive days. Twenty-four hours after the last (PhSe)2 dose, rats received PQ at 15 mg kg(-1), in a single intraperitoneally injection (i.p.). Seventy-two hours after PQ exposure, animals were sacrificed by decapitation for blood and liver samples obtainment. Histological alterations induced by PQ exposure, such as inflammatory cells infiltration and edema, were prevented by (PhSe)2 administration. Moreover, (PhSe)2 prevented hepatic lipid peroxidation (LPO) induced by PQ and was effective in reducing the myeloperoxidase (MPO) activity in liver, which was enhanced by PQ exposure. (PhSe)2 also was effective in protecting against the reduction in ascorbic acid and non-protein thiols (NPSH) levels induced by PQ. The inhibition of glutathione S-transferase (GST) activity, in rats exposed to PQ, was normalized by (PhSe)2 pre-treatment, whereas the inhibition of catalase (CAT) activity was not prevented by (PhSe)2. The serum alkaline phosphatase (ALP) inhibition, induced by PQ administration, was also prevented by (PhSe)2 pre-treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were not modified by PQ and/or (PhSe)2 administration. Therefore, (PhSe)2 pre-treatment was effective in protecting against the hepatic alterations induced by PQ in rats. This protective effect can involve the antioxidant and anti-inflammatory properties of (PhSe)2.

Effects of butane-2,3-dione thiosemicarbazone oxime on testicular damage induced by cadmium in mice.

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.