title: In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF).
abstract: The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg⁻¹ daily, for 2 weeks. Even at the highest concentration--a concentration highly toxic in vitro for all affected molds used, animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy.
authors: Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors: Zoltán
authors: Z
authors: Palicz
authors: Agnes
authors: A
authors: Jenes
authors: Tamás
authors: T
authors: Gáll
authors: Kornél
authors: K
authors: Miszti-Blasius
authors: Sándor
authors: S
authors: Kollár
authors: Ilona
authors: I
authors: Kovács
authors: Miklós
authors: M
authors: Emri
authors: Teréz
authors: T
authors: Márián
authors: Eva
authors: E
authors: Leiter
authors: István
authors: I
authors: Pócsi
authors: Eva
authors: E
authors: Csősz
authors: Gergő
authors: G
authors: Kalló
authors: Csaba
authors: C
authors: Hegedűs
authors: László
authors: L
authors: Virág
authors: László
authors: L
authors: Csernoch
authors: Péter
authors: P
authors: Szentesi
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005656:Fungal Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010408:Penicillium chrysogenum / Q000378:metabolism*; D049268:Positron-Emission Tomography; D018570:Risk Assessment; D012867:Skin / Q000187:drug effects; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; C097832:PAF protein, Penicillium chrysogenum