Objectives: Host chitinases, chitotriosidase and AMCase, improved the antifungal activity of caspofungin (CAS) against Aspergillus fumigatus in vitro. These chitinases are not constitutively expressed in the lung. Here we investigated whether chitosan derivatives were able to induce chitinase activity in the lungs of neutropenic rats and, if so, these chitinases were able to prolong survival rats with invasive pulmonary aspergillosis (IPA) or rats with IPA and treated with CAS.
Methods: An Oligosaccharide-lactate chitosan (OLC) derivative was instilled in the left lung of neutropenic rats to induce chitotriosidase and AMCase activity. Rats instilled with OLC or with PBS were subsequently infected with A. fumigatus and then treated with suboptimal doses of CAS. Survival, histopathology and galactomannan indexes were determined.
Results: Instillation of OLC resulted in chitotriosidase and AMCase activity. However, instillation of OLC did not prolong rat survival when subsequently challenged with A. fumigatus. In 5 out of 7 rats instilled with OLC, the fungal foci in the lungs were smaller than in rats instilled with PBS. Instillation OLC did not significantly enhance the survival of neutropenic rats challenged with A. fumigatus and treated with a sub-optimal dosage of CAS.
Conclusion: chitotriosidase and AMCase activity can be induced with OLC, but the presence of active chitinases in the lung did not prevent the development of IPA nor significantly enhanced the therapeutic outcome of CAS treatment.
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