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Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine

  • Authors:
    • Natalia E. Cortez
    • Cecilia Rodriguez Lanzi
    • Payam Vahmani
    • Karen Matsukuma
    • Gerardo G. Mackenzie

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  • Published online on: September 22, 2023     https://doi.org/10.3892/ol.2023.14067
  • Article Number: 479

  • Copyright: © Cortez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ketogenic diets (KDs) are actively being evaluated for their potential anticancer effects. Although KDs are generally considered safe, their safety profile when combined with chemotherapy remains unknown. It is known that a KD enhances the anticancer effect of gemcitabine (2',2'‑difluoro‑2'‑deoxycytidine) in LSL‑KrasLSL‑G12D/+Trp53R172H/+Pdx‑1-Cre (KPC) tumor‑bearing mice. In the present study, whether a KD in combination with gemcitabine affected the liver safety profile in KPC mice was evaluated. For this purpose, male and female pancreatic tumor‑bearing KPC mice were allocated to a control diet (CD; % kcal: 20% fat, 65% carbohydrate, 15% protein) + gemcitabine [control plus gemcitabine group (CG)] or a KD (% kcal: 84% fat, 15% protein, 1% carbohydrate) + gemcitabine [ketogenic plus gemcitabine group (KG)] for two months. After two months of treatment, no significant differences in body weight were observed between CGs and KGs. Moreover, the KD did not significantly alter the serum protein expression levels of liver enzymes, including aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. In addition, the KD did not alter markers of liver‑lipid accumulation as well as serum cholesterol and triglyceride levels, compared with the CG‑treated group. Upon histologic examination, steatosis was rare, with no notable differences between treatment groups. When examining liver fatty acid composition, KD treatment significantly increased the content of saturated fatty acids and significantly decreased levels of cis‑monounsaturated fatty acids compared with the CG. Finally, the KD did not affect liver markers of inflammation and oxidative stress, nor the protein expression levels of enzymes involved in ketone bodies, such as 3‑hydroxy‑3‑methylglutaryl‑CoA lyase and hidroximetilglutaril‑CoA sintasa, and glucose metabolism, such as hexokinase 2, pyruvate dehydrogenase and phosphofructokinase. In summary, a KD in combination with gemcitabine appears to be safe, with no apparent hepatotoxicity and these data support the further evaluation of a KD as an adjuvant dietary treatment for pancreatic cancer.
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November-2023
Volume 26 Issue 5

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Spandidos Publications style
Cortez NE, Lanzi CR, Vahmani P, Matsukuma K and Mackenzie GG: Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine. Oncol Lett 26: 479, 2023
APA
Cortez, N.E., Lanzi, C.R., Vahmani, P., Matsukuma, K., & Mackenzie, G.G. (2023). Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine. Oncology Letters, 26, 479. https://doi.org/10.3892/ol.2023.14067
MLA
Cortez, N. E., Lanzi, C. R., Vahmani, P., Matsukuma, K., Mackenzie, G. G."Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine". Oncology Letters 26.5 (2023): 479.
Chicago
Cortez, N. E., Lanzi, C. R., Vahmani, P., Matsukuma, K., Mackenzie, G. G."Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine". Oncology Letters 26, no. 5 (2023): 479. https://doi.org/10.3892/ol.2023.14067