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3224635 
Journal Article 
In vitro safety assessment of food ingredients in canine renal proximal tubule cells 
Koci, J; Jeffery, B; Riviere, JE; Monteiro-Riviere, NA 
2015 
1 
Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 
29 
2 
289-298 
English 
25458622 
WOS:000348625200003 
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 (0.012 mg/ml), while SORB the least toxic (>100 mg/ml). Toxicities (LC50) of positive controls were as follows: 4-aminophenol (0.15 mg/ml in CPTC and 0.083 mg/ml in human PTC), neomycin (28.6 mg/ml in CPTC and 27.1 mg/ml in human PTC). XYL displayed lowest cytotoxic potency (LC50 = 82.7 mg/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 (similar to 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. (C) 2014 Elsevier Ltd. All rights reserved. 
Food ingredients; Canine; Proximal tubule cells; Lemongrass oil; Gene expression; Metabolic pathway