Safety assessment of potential food ingredients in canine hepatocytes

Zhang, Leshuai W.; Koči, Juraj; Jeffery, Brett; Riviere, Jim E.; Monteiro‐Riviere, Nancy A.

doi:10.1016/j.fct.2015.02.003

Cited by 8 publications

(12 citation statements)

References 53 publications

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“…They are useful for probing mechanisms of toxicity in specific cell types when in vivo exposure is known to produce poisoning. In fact, this is consistent with our use of aflatoxin B1 and 4-aminophenol as positive controls when we developed these assays in hepatocytes 6 and in proximal tubule cells, 7 respectively. There is an ethical concern in conducting a hazard assessment in dogs for products destined for use in dogs.…”

Section: Discussionsupporting

confidence: 84%

“…4). Table 1 is a tabulation of the LC 50 for the compounds reported, as well as those previously reported for the canine renal proximal tubule cells, 7 hepatocytes, 6 BMSC, and ELC. 8 Correlation coefficients for regression analyses between the liver (as reference for all compounds for which statistically valid LC 50 values could be obtained) and kidney cells, between the liver cells and ELC, and between the liver cells and BMSC were 0.934, 0.991, and 0.990, respectively (all p < 0.0001).…”

Section: Resultsmentioning

confidence: 98%

“…As previously reported, gene expression arrays suggested oxidative stress as the primary mechanism in renal cells, in contrast to hepatocytes and BMSC, which showed upregulation of cytochrome P450 enzymes, and ELC showed upregulation of genes involved in heat shock response, beta oxidation, and mitochondrial energy metabolism. [6][7][8] The relevance of single-compound cytotoxicity data to effects observed when included in food is also difficult to predict because interactions with other food constituents (e.g., binding and chemical reactions) may occur. 63 Food served as a protective mechanism in the GTE exposures discussed above.…”

Section: Discussionmentioning

confidence: 99%

“…The methods used to harvest and culture the cells have been described in great detail in the previous publications for canine primary renal proximal tubule cells of the kidney, 7 canine hepatocytes for the liver, 6 and BMSC and ELC differentiation. 8 For all systems, cells were seeded on 96-well plates and test chemicals dosed at concentrations limited by specific chemical solubility in medium (n = 3 for hepatocytes and n = 6 for proximal tubule cells, BMSC, and ELC wells/concentration) for 24 hr.…”

Section: Cell Culture Methodsmentioning

confidence: 99%

“…The previous articles should be consulted for more specific details on the background of the original ingredients tested. [6][7][8] DB is a bittering agent used to enhance bitter flavor, as an aversive additive in household products to discourage consumption of poisonous substances, and also in cosmetics as a denaturant. The human bitterness threshold is 0.05 ppm for the benzoate form of denatonium.…”

Section: Introductionmentioning

confidence: 99%

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Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells

Monteiro‐Riviere

OrtegaMaria

ChoiKyoungju

et al. 2015

Applied In Vitro Toxicology

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To begin development of a mechanistically relevant humane alternative platform for safety assessment of dog food ingredients, comparative in vitro cytotoxicity of 20 ingredients was assessed in four canine cell types relevant for toxicity assessments. Previously, we described the toxicity of 13 compounds (clove leaf oil, eugenol, guanosine monophosphate [GMP], GMP plus inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol, lemon grass oil, xylitol, and citric acid) using in vitro primary canine cell culture models for liver, kidney, bone marrow-derived mesenchymal stem cells (BMSC), and enterocyte-like cells (ELC). In this report, dose-response cytotoxicity studies and LC 50 using alamar blue assays are reported for seven additional compounds: denatonium benzoate, eucalyptol, hexahydroisohumulone, tetrahydroisohumulone, green tea catechin extract, epigallocatechin gallate, and sodium copper chlorophyllin. Data across 20 compounds were compared between different cell types and responses were not parallel, precluding the use of a single cell line for in vitro ingredient hazard assessment. Hepatocytes were most resistant to all compounds, consistent with their xenobiotic detoxification functions. BMSC and ELC showed an increase in sensitivity to the essential oils eucalyptol, eugenol, and thymol compared to renal cells and hepatocytes. These studies provide a baseline of acute cytotoxicity of 4 canine cell types to 20 different food components that begin to illustrate how such an in vitro panel could be used for hazard assessment.

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culture Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells

Monteiro‐Riviere

OrtegaMaria

ChoiKyoungju

et al. 2015

Applied In Vitro Toxicology

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Toxicological effects of pet food ingredients on canine bone marrow‐derived mesenchymal stem cells and enterocyte‐like cells

Ortega

Jeffery²,

Riviere

et al. 2015

J of Applied Toxicology

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We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml(-1) for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml(-1) for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml(-1) for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml(-1) for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml(-1) for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml(-1) for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml(-1) for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml(-1) for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml(-1) for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml(-1) for ginger root extract; > 200 and 116.78 ± 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003-0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells.

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Dry food affects the oxidative/antioxidant profile of dogs

Suarez

Rojano

Duque³

et al. 2023

Veterinary Medicine & Sci

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Background Including adequate concentrations of antioxidants in dog diets has been recommended to reduce their vulnerability to the action of free radicals and reactive oxygen species (ROS). Oxidative stress in dogs has been associated with a wide range of diseases and disorders, as well as with ageing. There are few reports about the influence of diet on dog's antioxidant profile and oxidative stress. Objective The objective of this study was to evaluate the effect of four types of dry dog food on the oxidative/antioxidant profile of dogs. Methods Six Beagle dog males were used. The study included four experimental diets (dry foods A–D). Each dry food was supplied for 5 weeks to all dogs, for a total of 24 weeks, including an adaptation week between one food and another. For each dry dog food, the total phenolic content (TPC), total antioxidant capacity (TAC) and cytotoxicity were evaluated. Each week, a blood sample was collected to measure ROS and TAC of plasma. A crossover repeated measures design was used. Mixed models were adjusted, and means were compared using the Tukey test. Results Food A had the highest values for TPC and TAC. Food C had the lowest levels of ROS, whereas food B had the highest TAC in the blood plasma. The dog had a significant influence on the redox state of its blood plasma, even when the same dog was fed the different dry foods. Conclusion Dry dog food influences the oxidative/antioxidant profile of dog's blood plasma; however, this seems to be unrelated to the antioxidant profile of the food.

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Safety assessment of potential food ingredients in canine hepatocytes

Cited by 8 publications

References 53 publications

Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells

Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells

Toxicological effects of pet food ingredients on canine bone marrow‐derived mesenchymal stem cells and enterocyte‐like cells

Dry food affects the oxidative/antioxidant profile of dogs

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