Optimization of bleomycin concentration in IPF rodent model

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Optimization of bleomycin concentration in IPF rodent model

Optimization of bleomycin concentration in IPF rodent model

Bleomycin (BLM) is the prevailing chemical treatment for inducing IPF in rodent models in view to study the efficacy of lead molecules. Literature data shows that a large part of histological, biochemical and functional investigations was performed with high bleomycin concentration (doses >1 mg/kg) involving a significant morbidity and mortality of BLM-treated animals.

Animal mortality: a key problem

These deleterious effects of high doses of BLM should be better considered when evaluating the effectiveness of lead molecules. Indeed, it can be assumed that an excessively high level of fibrosis in the positive control group (BLM-treated) might mask or alter the positive effect of pharmacological treatment induced in BLM-tested groups.
Considering the histological approach of IPF, the use of high doses of BLM is greatly related to the standard evaluation of pulmonary fibrosis based on Ashcroft scoring. Such a scoring evaluation, called semi-quantitative, indeed does not allow an accurate and reliable quantification of low levels of IPF.
The high precision of quantitative image analysis of IPF developed by Biocellvia allows to conduct an accurate and reliable quantification of IPF whatever its level. Consequently, we showed that BLM concentrations used for inducing IPF could be considerably reduced leading to a total removal of mortality and a much better physiological state of BLM-treated animals.

Body weight during experiment on bleomycin concentration

Reducing bleomycin concentration : a major need for the reliable assessment of lead molecules

In light of Biocellvia expertise and experience in quantitative image analysis of IPF we strongly recommend to optimize concentration of BLM in order to maintain in BLM-treated animals the optimum physiological state. The use of Biocellvia IPF assay™ allows to achieve this goal. Thanks to the high resolution for discriminating very low level of pulmonary fibrosis usual concentrations of BLM, used for scoring semiquantitative analysis, can be drastically decreased. A low BLM concentration of 0.25 mg/kg has been shown to be sufficient to induce well-quantifiable lung foci in mice. Biocellvia IPF assay™ can be leveraged to determine the efficacy of molecules in early-stage of IPF, which is not feasible from scoring evaluation.
By reducing the doses of BLM treatment (≤ 1 mg / kg), no mortality was observed in all BLM-treated animals.It is worth noting that the total suppression of mortality in all BLM-treated groups allows to reduce significantly the number of animals per group while providing a set of important data. Interestingly, at these low doses of BLM, lower weight loss was observed, reflecting the satisfactory physiological state of animals. As stated by Biocellvia scientists « The lower dose of BLM (>1 mg/kg) reduces the stress for the animals used and increases the chance for successful and reliable drug testing».

A new model is rising

Although the BLM rodent model cannot reproduce exactly all the features of IPF in humans it remains a reference model for the preclinical study of the efficacy of therapeutic molecules. Its use in preclinical studies, however, must be optimized by drastically reducing the concentration of BLM. This will allow a much more precise and reliable quantification of the effectiveness of lead molecules. Such a quantification cannot be carried out by means of scoring evaluation and necessitate a much more reliable measure of changes in morphological structure of pulmonary tissue. Only the histological numerical quantitative analysis such as that developed by Biocellvia provides access to this requirement.

Optimization of bleomycin concentration in IPF rodent model a key feature for unbiased assessment of the efficacy of lead molecules (this link enables you to download the PDF file)

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