Assessment of Toxicity of Nanoparticles Using Insects as Biological Models.

Nanomaterials have become increasingly important in medicine, manufacturing, and consumer products. A fundamental understanding of the effects of nanoparticles (NPs) and their interactions with biomolecules and organismal systems has yet to be achieved. In this chapter, we firstly provide a brief review of the interactions between nanoparticles and biological systems. We then provide an example by describing a novel method to assess the effects of NPs on biological systems, using insects as a model. Nanoparticles were injected into the central nervous system of the discoid cockroach (Blaberus discoidalis). It was found that insects became hyperactive compared to negative control (water injections). Our method could provide a generic method of assessing nanoparticles toxicity.

Central nervous system biogenic amine targets for control of appetite and energy expenditure.

Central biogenic amine systems have long been studied for their effects on feeding behavior, energy balance, and maintenance of body weight. Those monoaminergic systems that use dopamine (DA), norepinephrine (NE), and serotonin (5-hydroxytryptamine, 5-HT) as neurotransmitters have been the main targets of study. A number of antiobesity medications that affect monoaminergic activity have appeared on the market and/or in clinical trials. Early examples of such agents are the so-called CNS stimulants, e.g., the amphetamines, phentermine, ephedrine, etc. These agents release monoamines from neuronal stores, and their antiobesity activity seems to be tied most closely to their ability to release NE. Inhibitors of neuronal reuptake of NE or 5-HT have been shown to reduce feeding and weight gain both preclinically and clinically. However, the magnitude and sustainability of such effects in clinical trials has generally not been great enough to register or label these agents for the treatment of obesity. Sibutramine, however, is an exception. This compound is metabolized in vivo to produce metabolites that have varying degrees of inhibition of NE, 5-HT, and/or DA uptake. Sibutramine is the only drug affecting monoaminergic systems currently approved for the long-term control of obesity. Research continues on serotonergic and histaminergic systems to determine if targets such as the 5-HT2C and H3 receptors may be suitable for developing antiobesity agents. Because the clinical antiobesity effects of monoaminergic drugs have been modest, future directions include looking at combinations of different monoaminergic mechanisms and/or combinations of monoaminergic drugs with non-monoaminergic mechanisms.