title: Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties.
abstract: 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.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Costa
authors.forename: Bibiana M
authors.initials: BM
authors.lastname: Gai
authors.forename: Carmine I
authors.initials: CI
authors.lastname: Acker
authors.forename: Ana Cristina G
authors.initials: AC
authors.lastname: Souza
authors.forename: Ricardo
authors.initials: R
authors.lastname: Brandão
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001393:Azoles / Q000494:pharmacology*; D003976:Diazinon / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018716:Molecular Mimicry; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000110:Acetylcholinesterase; D000469:Alkaline Phosphatase; D005952:Glucose-6-Phosphatase; D003976:Diazinon