title: In vitro safety assessment of food ingredients in canine renal proximal tubule cells.
abstract: In vitro models are useful tools to initially assess the toxicological safety hazards of food ingredients. Toxicities of cinnamaldehyde (CINA), cinnamon bark oil, lemongrass oil (LGO), thymol, thyme oil (TO), clove leaf oil, eugenol, ginger root extract (GRE), citric acid, guanosine monophosphate, inosine monophosphate and sorbose (SORB) were assessed in canine renal proximal tubule cells (CPTC) using viability assay and renal injury markers. At LC50, CINA was the most toxic (0.012mg/ml), while SORB the least toxic (>100mg/ml). Toxicities (LC50) of positive controls were as follows: 4-aminophenol (0.15mg/ml in CPTC and 0.083mg/ml in human PTC), neomycin (28.6mg/ml in CPTC and 27.1mg/ml in human PTC). XYL displayed lowest cytotoxic potency (LC50=82.7mg/ml in CPTC). In vivo renal injury markers in CPTC were not significantly different from controls. The LGO toxicity mechanism was analyzed using qPCR and electron microscopy. Out of 370 genes, 57 genes (15.4%) were significantly up (34, 9.1%) or down (23, 6.2%) regulated, with the most upregulated gene gsta3 (∼200-fold) and the most affected pathway being oxidative stress. LGO induced damage of mitochondria, phospholipid accumulation and lack of a brush border. Viability assays along with mechanistic studies in the CPTC model may serve as a valuable in vitro toxicity screening tool.
authors.affiliation: Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States.
authors.forename: J
authors.initials: J
authors.lastname: Koči
authors.affiliation: Mars Global Food Safety Center, Yanqi Economic Development Zone, Huairou, 101407 Beijing, PR China.
authors.forename: B
authors.initials: B
authors.lastname: Jeffery
authors.affiliation: Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States.
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
authors.affiliation: Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States. Electronic address: nmonteiro@ksu.edu.
authors.forename: N A
authors.initials: NA
authors.lastname: Monteiro-Riviere
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000633:toxicity; D000627:Aminophenols / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000633:toxicity; D004285:Dogs; D005054:Eugenol / Q000633:toxicity; D059022:Food Safety; D020869:Gene Expression Profiling; D020939:Zingiber officinale; D006157:Guanosine Monophosphate / Q000633:toxicity; D006801:Humans; D007291:Inosine Monophosphate / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D009822:Oils, Volatile / Q000633:toxicity; D010936:Plant Extracts / Q000633:toxicity; D010938:Plant Oils / Q000633:toxicity; D018517:Plant Roots; D013013:Sorbose / Q000633:toxicity; D013729:Terpenes / Q000633:toxicity; D013943:Thymol / Q000633:toxicity; D046930:Thymus Plant; D018675:Toxicity Tests / Q000379:methods*; D014993:Xylitol / Q000633:toxicity
chemical_list: D000627:Aminophenols; D009822:Oils, Volatile; D010936:Plant Extracts; D010938:Plant Oils; D013729:Terpenes; C510046:cinnamon oil, bark; D007291:Inosine Monophosphate; D019343:Citric Acid; D013943:Thymol; D005054:Eugenol; C052901:lemongrass oil; D000171:Acrolein; D006157:Guanosine Monophosphate; D013013:Sorbose; C026729:4-aminophenol; C012843:cinnamaldehyde; D014993:Xylitol
keywords: Canine; Food ingredients; Gene expression; Lemongrass oil; Metabolic pathway; Proximal tubule cells