title: Preliminary safety assessment of Yarrowia lipolytica extracellular lipase: results of acute and 28-day repeated dose oral toxicity studies in rats.
abstract: Interest in extracellular lipase sourced from the non conventional yeast Yarrowia lipolytica has increased over the last decade. The enzyme was recently suggested as a good candidate for pancreatic exocrine insufficiency treatment. However, there is still a lack of oral safety evaluation data. In this work, we conducted acute and 28-day repeated dose toxicity studies in rats. Both male and female rats were first orally treated with fungal lipase at either single or repeated doses. The results demonstrated that neither single dose nor chronic administration of lipase was associated with mortality or abnormalities in general conditions, behavior and growth. Except a decrease in urine pH and a dose-unrelated increase of triglycerides observed in males, chronic administration of lipase resulted in similar hematological, blood biochemical and urine parameters to those of untreated animals. Minor histopathological changes were observed in lungs and livers of treated and untreated animals but they were considered of no toxicological significance. This study provides, for the first time, safety data on Yarrowia lipolytica extracellular lipase that support its use as a pharmaceutical.
authors.affiliation: Fermentation Unit, Institut Pasteur de Tunis, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Turki
authors.forename: Zeineb
authors.initials: Z
authors.lastname: Jabloun
authors.forename: Ghada
authors.initials: G
authors.lastname: Mrabet
authors.forename: Ammar
authors.initials: A
authors.lastname: Marouani
authors.forename: Philippe
authors.initials: P
authors.lastname: Thonart
authors.forename: Mohammed Fethi
authors.initials: MF
authors.lastname: Diouani
authors.forename: Fethi
authors.initials: F
authors.lastname: Ben Abdallah
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Amara
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rejeb
authors.forename: Héla
authors.initials: H
authors.lastname: Kallel
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D008049:Lipase / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012449:Safety; D012727:Sex Characteristics; D016019:Survival Analysis; D016482:Urinalysis; D015430:Weight Gain / Q000187:drug effects; D025062:Yarrowia / Q000737:chemistry*
chemical_list: D008049:Lipase