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

• Published in: Chemico-biological interactions 2012-05, Vol.197 (2-3), p.80-86
• Main Authors: Costa, Michael D., Gai, Bibiana M., Acker, Carmine I., Souza, Ana Cristina G., Brandão, Ricardo, Nogueira, Cristina W.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; alanine transaminase; Alanine Transaminase - blood; alkaline phosphatase; Alkaline Phosphatase - blood; Animals; Aspartate Aminotransferases - blood; aspartate transaminase; Azoles - pharmacology; blood glucose; blood serum; diazinon; Diazinon - toxicity; Ebselen; Erythrocytes - drug effects; Erythrocytes - enzymology; glucose; glucose-6-phosphatase; Glucose-6-Phosphatase - metabolism; glycemic effect; glycogen; Hepatic; Hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; in vitro studies; in vivo studies; insulin; Insulin-mimetic; L-Lactate Dehydrogenase - blood; lactate dehydrogenase; Liver - drug effects; Liver - metabolism; Male; Molecular Mimicry; Organophosphate; Organoselenium Compounds - pharmacology; Pancreas - drug effects; Pancreas - metabolism; Pancreatic; pretreatment; protective effect; Rats; Rats, Wistar; skeletal muscle
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2012.03.008

► Ebselen reduced hyperglycemia and increased hepatic glycogen altered by diazinon. ► Ebselen prevented pancreatic and hepatic damage caused by diazinon. ► Ebselen possesses insulin-mimetic action. 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 (200mg/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 (150μM) or insulin (IN 10μM, 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.