Preliminary safety assessment of Yarrowia lipolytica extracellular lipase: results of acute and 28-day repeated dose oral toxicity studies in rats.
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.
Turki
Saoussen
S
Fermentation Unit, Institut Pasteur de Tunis, Tunisia.
Jabloun
Zeineb
Z
Mrabet
Ghada
G
Marouani
Ammar
A
Thonart
Philippe
P
Diouani
Mohammed Fethi
MF
Ben Abdallah
Fethi
F
Amara
Abdelkader
A
Rejeb
Ahmed
A
Kallel
Héla
H
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*
D008049:Lipase