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.

Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties.

The present study investigated the effect of ebselen (EB) against hyperglycemia induced by the organophosphate (OPI) diazinon (DI) in rats. The insulin-mimetic properties of EB were investigated in vitro with the aim of better understanding the hypoglycemic effect of this compound. The protective effect of EB against pancreatic and hepatic damage caused by DI in rats was also appraised. In the in vivo experiments, rats were pre-treated with a single injection of EB (50mg/kg, intraperitoneal, i.p.). Afterward, animals were treated with a single injection of DI (200 mg/kg, i.p.). The parameters indicative of pancreatic and hepatic damage such as, serum amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities as well as serum glucose levels, hepatic glycogen content and glucose-6-phosphatase (G6Pase) activity were determined. EB pre-treatment was effective in reducing serum amylase, lipase, AST, ALT, ALP, and LDH activities, protecting against pancreatic and hepatic damage. EB reduced hyperglycemia and increased hepatic glycogen content in animals exposed to DI. In the in vitro assays, EB (150 µM) or insulin (IN 10 µM, positive control) was incubated with either skeletal muscle or hepatic tissue with the aim of measuring glucose uptake, glycogen synthesis and glycogen breakdown. EB increased the glucose uptake in skeletal muscle, stimulated hepatic glycogen synthesis and inhibited glycogen breakdown in a similar way to IN. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats.

Potential of two new oximes in reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by organophosphate compounds: an in vitro study.

Organophosphate (OP) compounds exert inhibition on cholinesterase (ChE) activity by irreversibly binding to the catalytic site of the enzyme. Oximes are compounds generally used to reverse the ChE inhibition caused by OP agents. In this study, we compared the in vitro reactivation potency of two new oximes (oxime 1: butane-2,3-dionethiosemicarbazone; oxime 2: 3-(phenylhydrazono) butan-2-one) against the inhibition on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities induced by chlorpyrifos, diazinon and malathion. Oximes used clinically (obidoxime and pralidoxime) were used as positive control. For this study, human blood (erythrocytes for AChE determination and plasma for BChE determination) was used and different concentrations of oximes (1-100 µM) were tested. The concentrations of OP used were based on the IC50 for AChE and BChE. Results demonstrated that obidoxime was more effective in reactivate the AChE inhibition induced by OP compounds. However, both newly developed oximes achieved similar reactivations rates that pralidoxime for chlorpyrifos and diazinon-inhibited AChE. For BChE reactivation, none of evaluated oximes achieved positives rates of reactivation, been obidoxime able to reactivate malathion-inhibited BChE only in 24% at the highest concentration. We conclude that both newly developed oximes seem to be promising reactivators of OP-inhibited AChE.

FeCl(3)-Diorganyl dichalcogenides promoted cyclization of 2-alkynylanisoles to 3-chalcogen benzo[b]furans.

A general synthesis of 3-chalcogen benzo[b]furans from the readily available 2-alkynylanisoles, via FeCl(3)/diorganyl dichalcogenides intramolecular cyclization, has been developed. Aryl and alkyl groups directly bonded to the chalcogen atom were used as cycling agents. The results revealed that the reaction significantly depends on the electronic effects of substituents in the aromatic ring bonded to the selenium atom of the diselenide species. We observed that the pathway of reaction was not sensitive to the nature of substituents in the aromatic ring of anisole since both the electron-donating and the electron-withdrawing groups delivered the products in similar yields. In addition, the obtained heterocycles were readily transformed to more complex products by using a chalcogen/lithium exchange reaction with n-BuLi followed by trapping of the lithium intermediate with aldehydes, furnishing the desired secondary alcohols in good yields.