Study of antidiabetic activity of two novel Schiff base derived dibromo and dichloro substituted compounds in streptozotocin-nicotinamide-induced diabetic rats: pilot study

Abstract Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat's liver and can be responsible for causing much healthier structure and notable morphology improvement.

Intracerebroventricular Administration of Streptozotocin as an Experimental Approach to Depression: Evidence for the Involvement of Proinflammatory Cytokines and Indoleamine-2,3-Dioxygenase.

There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test. Indirect blockade of IDO activation with the cytokine inhibitor minocycline prevents the development of depressive-like behaviors and attenuates STZ-induced upregulation of proinflammatory cytokines in the hippocampus. Minocycline abrogates the increase in tryptophan and kynurenine levels as well as prevents serotonin dysfunction in the hippocampus of STZ-injected mice. These results suggest that hippocampal IDO activation in STZ-associated depressive-like behavior is mediated by proinflammatory cytokine-dependent mechanisms. Our study not only extends the evidence that IDO has a critical role in mediating inflammation-induced depression but also supports the notion that neuroinflammation and the kynurenine pathway are important targets of novel therapeutic drugs for depression. In addition, our study provides new insights into the neurobiological mechanisms underlying ICV-STZ and indicates that this model could be employed in the preclinical research of depression.

Administration of branched-chain amino acids reduces the diabetogenic effect of streptozotocin in rats.

1. Previous work has shown that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet and that plasma valine, leucine and isoleucine concentrations are markedly elevated in rats adapted to the high-protein diet. 2. To test the possibility that these branched-chain amino acids play a role in the beneficial effects of the high-protein diet, rats fed the control balanced diet were injected intraperitoneally with mixtures of valine, leucine and isoleucine (0.25 or 0.50 g/kg body weight of each amino acid), or with each of these amino acids separately (0.50 g/kg), 15 min before streptozotocin administration (40 mg/kg, intravenously). Arginine (0.50 g/kg) was administered in one experiment. Control animals received equal volumes of saline. 3. Rats previously injected with the amino acid mixtures showed a partial but significant reduction of diabetes severity as indicated by lower plasma glucose levels, higher rates of body weight gain and greater amounts of epididymal and retroperitoneal fat. No protection was observed after the administration of either valine, isoleucine, leucine or arginine. 4. These data suggest that the elevated levels of plasma branched-chain amino acids may account at least in part for the initial protective effect of high-protein diets against streptozotocin beta-cytotoxicity when the cells are first exposed to the drug.