Atrial natriuretic peptides in Han Wistar, Sprague-Dawley and spontaneously hypertensive rats.

The atrial natriuretic peptide (ANP) and its precursor (N-terminal fragment of atrial natriuretic peptide, NT-proANP) are natriuretic peptides released into the circulation as a consequence of an acute atrial stretch. As for the brain natriuretic peptide and its N-terminal fragment, the biological significance of ANP and NT-proANP has been widely studied in humans, but the literature is lacking information about the determination of these biomarkers in veterinary medicine and, in particular, in the toxicological species used in preclinical pharmaceutical drug development. This paper describes the evaluation of ANP and NT-proANP levels in a healthy population of Han Wistar and Sprague-Dawley rats, as well as in a rodent model of hypertension (Spontaneously Hypertensive rats).

Capillary electrophoresis for the detection of bilirubin in rat serum.

Background: The rat is used often to assess the toxicity of new chemical entities in preclinical drug development. Bilirubin concentration in rat serum is routinely determined by colorimetric methods, but false positive results due to hemolyzed serum or direct interferences by test compounds may occur. Capillary electrophoresis (CE) is an automated method that requires small sample volume and facilitates the direct detection of bilirubin.

Toward refinement of the colony-forming unit-granulocyte/macrophage clonogenic assay: inclusion of a metabolic system.

This work represents a first attempt to refine the colony-forming unit-granulocyte/macrophage (CFU-GM) clonogenic assay by incorporating liver microsomes and co-factors as a metabolic system into the in vitro test system in response to an ECVAM recommendation. From the comparison of results obtained with the CFU-GM clonogenic assay currently used and with the new experimental protocol, different toxicity on granulocyte/macrophage precursors was demonstrated, when drugs with a known metabolism in vivo were tested.

A new experimental protocol as an alternative to the colony-forming unit-granulocyte/macrophage (CFU-GM) clonogenic assay to assess the haematotoxic potential of new drugs.

In this work, a first attempt to set-up a new in vitro experimental protocol with culture in liquid medium and flow cytometry analysis of bone marrow progenitors is described. This protocol is proposed as an alternative to the colony-forming unit-granulocyte/macrophage (CFU-GM) clonogenic in vitro assay currently used to assess the toxic potential of new drugs in the bone marrow. This new experimental approach should enable to speed up the procedure of the in vitro haematotoxic potential assessment, to reduce inter-experimental variability and to enhance result accuracy.