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Rojas-Morales P, León-Contreras JC, Sánchez-Tapia M, et al. A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation. Life Sci. 2021;289:120227doi: 10.1016/j.lfs.2021.120227.
Rojas-Morales, P., León-Contreras, J. C., Sánchez-Tapia, M., Silva-Palacios, A., Cano-Martínez, A., González-Reyes, S., Jiménez-Osorio, A. S., Hernández-Pando, R., Osorio-Alonso, H., Sánchez-Lozada, L. G., Tovar, A. R., Pedraza-Chaverri, J., & Tapia, E. (2021). A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation. Life sciences, 289120227. https://doi.org/10.1016/j.lfs.2021.120227
Rojas-Morales, Pedro, et al. "A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation." Life sciences vol. 289 (2021): 120227. doi: https://doi.org/10.1016/j.lfs.2021.120227
Rojas-Morales P, León-Contreras JC, Sánchez-Tapia M, Silva-Palacios A, Cano-Martínez A, González-Reyes S, Jiménez-Osorio AS, Hernández-Pando R, Osorio-Alonso H, Sánchez-Lozada LG, Tovar AR, Pedraza-Chaverri J, Tapia E. A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation. Life Sci. 2021 Dec 16;289:120227. doi: 10.1016/j.lfs.2021.120227. Epub 2021 Dec 16. PMID: 34921866.
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Life Sci. 2021 Dec 16;289:120227. doi: 10.1016/j.lfs.2021.120227. Epub 2021 Dec 16.

A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation.

Life sciences

Pedro Rojas-Morales, Juan Carlos León-Contreras, Mónica Sánchez-Tapia, Alejandro Silva-Palacios, Agustina Cano-Martínez, Susana González-Reyes, Angélica Saraí Jiménez-Osorio, Rogelio Hernández-Pando, Horacio Osorio-Alonso, Laura Gabriela Sánchez-Lozada, Armando R Tovar, José Pedraza-Chaverri, Edilia Tapia

Affiliations

  1. Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico; Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
  2. Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico.
  3. Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico.
  4. Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico.
  5. Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico.
  6. Facultad de Medicina y Psicología, Universidad Autónoma de Baja California, Tijuana 22390, Mexico.
  7. Área Académica de Enfermería, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico.
  8. Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico.
  9. Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
  10. Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico. Electronic address: [email protected].

PMID: 34921866 DOI: 10.1016/j.lfs.2021.120227

Abstract

BACKGROUND: Ischemic kidney injury is a common clinical condition resulting from transient interruption of the kidney's normal blood flow, leading to oxidative stress, inflammation, and kidney dysfunction. The ketogenic diet (KD), a low-carbohydrate, high-fat diet that stimulates endogenous ketone body production, has potent antioxidant and anti-inflammatory effects in distinct tissues and might thus protect the kidney against ischemia and reperfusion (IR) injury.

MAIN METHODS: Male Wistar rats were fed a KD or a control diet (CD) for three days before analyzing metabolic parameters or testing nephroprotection. We used two different models of kidney IR injury and conducted biochemical, histological, and Western blot analyses at 24 h and two weeks after surgery.

KEY FINDINGS: Acute KD feeding caused protein acetylation, liver AMPK activation, and increased resistance to IR-induced kidney injury. At 24 h after IR, rats on KD presented reduced tubular damage and improved kidney functioning compared to rats fed with a CD. KD attenuated oxidative damage (protein nitration, 4-HNE adducts, and 8-OHdG), increased antioxidant defenses (GPx and SOD activity), and reduced inflammatory intermediates (IL6, TNFα, MCP1), p50 NF-κB expression, and cellular infiltration. Also, KD prevented interstitial fibrosis development at two weeks, up-regulation of HSP70, and chronic Klotho deficiency.

SIGNIFICANCE: Our findings demonstrate for the first time that short-term KD increases tolerance to experimental kidney ischemia, opening the opportunity for future therapeutic exploration of a dietary preconditioning strategy to convey kidney protection in the clinic.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Inflammation; Ketogenic diet; Ketosis; Kidney fibrosis; Kidney ischemia; Oxidative stress

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