The use of proteomic techniques to explore the holistic effects of nutrients in vivo

The availability of ‘omics’ technologies is transforming scientific approaches to physiological problems from a reductionist viewpoint to that of a holistic viewpoint. This is of profound importance in nutrition, since the integration of multiple systems at the level of gene expression on the synthetic side through to metabolic enzyme activity on the degradative side combine to govern nutrient availability to tissues. Protein activity is central to the process of nutrition from the initial absorption of nutrients via uptake carriers in the gut, through to distribution and transport in the blood, metabolism by degradative enzymes in tissues and excretion through renal tubule exchange proteins. Therefore, the global profiling of the proteome, defined as the entire protein complement of the genome expressed in a particular cell or organ, or in plasma or serum at a particular time, offers the potential for identification of important biomarkers of nutritional state that respond to alterations in diet. The present review considers the published evidence of nutritional modulation of the proteome in vivo which has expanded exponentially over the last 3 years. It highlights some of the challenges faced by researchers using proteomic approaches to understand the interactions of diet with genomic and metabolic–phenotypic variables in normal populations.

Aminoglycoside-induced changes in the renal handling of cations in the Fischer 344 rat

Disturbances of cation homeostasis, particularly hypomagnesaemia, are a frequent consequence of treatment with aminoglycoside antibiotics. These disturbances are thought to result from renal wasting of cations and administration of gentamicin to rats has been shown to produce hypercalciuria and hypermagnesiuria. The aims of this study were to attempt to elucidate these responses in anaesthetised rats infused with gentamicin and to use this model to investigate the mechanisms of these effects. Fischer 344 rats were anaesthetised and surgically prepared for clearance experiments. Infusion of gentamicin in isotonic saline increased urinary output of calcium and magnesium while sodium and potassium output were unaffected. These elevations in calcium and magnesium excretion were explained by reduced tubular reabsorption of these cations. Both the hypercalciuric and hypermagnesiuric responses to gentamicin were extremely rapid and were sustained during drug infusion; when gentamicin infusion ceased both responses were rapidly reversible. Infusion of another aminoglycoside, tobramycin, produced very similar effects to gentamicin. The hypercalciuria and hypermagnesiuria caused by gentimicin infusion were unaffected by parathyroidectomy. The peak increases in calcium and magnesium output brought about by infusion of gentamicin with frusemide were not significantly different to the increases produced by frusemide alone. The site at which gentamicin interferes with calcium and magnesium reabsorption cannot be firmly deduced from these results. However, the known close association between calcium and sodium reabsorption in the proximal tubule implies that gentamicin is unlikely to change proximal calcium reabsorption without a similar change in proximal sodium reabsorption. The similarity between the hypercalciuric and hypermagnesiuric effects of frusemide alone and the effects of frusemide infused simultaneously with gentamicin suggests that gentamicin may act at the same site as the diuretic, the thick ascending limb of the loop of Henle.