Effects of Ketogenic and Western Diets on Proliferation, Vasculogenesis and Oxidative Stress in the Liver

Year 2021, Volume: 38 Issue: 3, 312 - 317, 01.05.2021

Songül Doğanay , Özcan Budak , Nurten Bahtiyar , Veysel Toprak

Abstract

Objective: In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue.
Materials and Methods: BALBC female rats (21) were divided as the group fed with standard chow (SC), the group fed with a ketogenic diet (KD) and the group fed with western diet (WD). The rats were fed with tap water and a rat diet specially prepared according to the determined diets for 4 weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods.
Results: At the end of the experiment, it was found that the highest weight gain was in the WD group and the least weight gain was in the KD group. The mean body weight of the WD group was statistically significantly higher compared to the SC and KD groups (p<0.05). MDA levels were found to be lower in the KD group compared to the SC and WD groups. GSH and CAT levels were higher in the KD group compared to the SC and WD groups. In IHC evaluation results, it was seen that Ki-67 percentage in the KD group increased compared to the WD and SC groups (p = 0.000), VEGF was close to each other in all three groups and there was no significant difference in the comparisons between groups (p>0.05).
Conclusion: These results revealed that ketogenic diet prevents tissue damage by decreasing lipid peroxidation in liver tissue as well as inducing cellular proliferation and vasculogenesis.

Keywords

Ketogenic diet, oxidative stress, proliferation, vasculogenesis

References

• Allen, B.G., Bhatia, S.K., Buatti, J.M., Brandt, K.E., Lindholm, K.E., Button, A.M., Szweda, L.I., Smith, B.J., Spitz, D.R., Fath, M.A., 2013. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clinical Cancer Research. 19, 3905-3913.
• Apel, K., Hirt, H., 2004. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu. Rev. Plant Biol. 55, 373-399.
• Baena, M., Sangüesa, G., Hutter, N., Beltrán, J.M., Sánchez, R.M., Roglans, N., Alegret, M., Laguna, J.C., 2017. Liquid fructose in Western-diet-fed mice impairs liver insulin signaling and causes cholesterol and triglyceride loading without changing calorie intake and body weight. The Journal of nutritional biochemistry. 40, 105-115.
• Beers, R.F., Sizer, I.W., 1952. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol chem. 195, 133-140.
• Beutler, E., 1963. Improved method for the determination of blood glutathione. J. lab. clin. Med. 61, 882-888.
• Boison, D., 2017. New insights into the mechanisms of the ketogenic diet. Current opinion in neurology. 30, 187.
• Buege, J., Aust, S., 1978. Microsomal lipid peroxidation Methods Enzymol 52: 302–310. Find this article online. Fleet, J.C., 2014. Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer. American Journal of Physiology-Gastrointestinal and Liver Physiology. 307, G249-G259.
• Freeman, J.M., Kossoff, E.H., 2010. Ketosis and the ketogenic diet, 2010: advances in treating epilepsy and other disorders. Advances in pediatrics. 57, 315-329.
• Garcia‐Fuentes, E., Murri, M., Garrido‐Sanchez, L., Garcia‐Serrano, S., García‐Almeida, J.M., Moreno‐Santos, I., Tinahones, F.J., Macias‐Gonzalez, M., 2010. PPARγ Expression After a High‐fat Meal Is Associated With Plasma Superoxide Dismutase Activity in Morbidly Obese Persons. Obesity. 18, 952-958.
• Greco, T., Glenn, T.C., Hovda, D.A., Prins, M.L., 2016. Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. Journal of Cerebral Blood Flow & Metabolism. 36, 1603-1613.
• Hariharan, D., Vellanki, K., Kramer, H., 2015. The Western diet and chronic kidney disease. Current hypertension reports. 17, 16.
• Harmancey, R., Wilson, C.R., Wright, N.R., Taegtmeyer, H., 2010. Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis. Journal of lipid research. 51, 1380-1393.
• Hazan, C., Melzer, K., Panageas, K.S., Li, E., Kamino, H., Kopf, A., Cordon‐Cardo, C., Osman, I., Polsky, D., 2002. Evaluation of the proliferation marker MIB‐1 in the prognosis of cutaneous malignant melanoma. Cancer: Interdisciplinary International Journal of the American Cancer Society. 95, 634-640.
• Heinonen, I., Rinne, P., Ruohonen, S., Ruohonen, S., Ahotupa, M., Savontaus, E., 2014. The effects of equal caloric high fat and western diet on metabolic syndrome, oxidative stress and vascular endothelial function in mice. Acta Physiologica. 211, 515-527.
• Jarrett, S.G., Milder, J.B., Liang, L.P., Patel, M., 2008. The ketogenic diet increases mitochondrial glutathione levels. Journal of neurochemistry. 106, 1044-1051.
• Jenkins, T.A., Nguyen, J.C., Hart, J.L., 2016. Decreased vascular H 2 S production is associated with vascular oxidative stress in rats fed a high-fat western diet. Naunyn-Schmiedeberg's archives of pharmacology. 389, 783-790.
• Kephart, W.C., Mumford, P.W., Mao, X., Romero, M.A., Hyatt, H.W., Zhang, Y., Mobley, C.B., Quindry, J.C., Young, K.C., Beck, D.T., 2017. The 1-week and 8-month effects of a ketogenic diet or ketone salt supplementation on multi-organ markers of oxidative stress and mitochondrial function in rats. Nutrients. 9, 1019.
• Krenkel, O., Tacke, F., 2017. Liver macrophages in tissue homeostasis and disease. Nature Reviews Immunology. 17, 306-321.
• Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. Journal of biological chemistry. 193, 265-275.
• Lu, Y., Yang, Y.-Y., Zhou, M.-W., Liu, N., Xing, H.-Y., Liu, X.-X., Li, F., 2018. Ketogenic diet attenuates oxidative stress and inflammation after spinal cord injury by activating Nrf2 and suppressing the NF-κB signaling pathways. Neuroscience Letters. 683, 13-18.
• Mazzoli, A., Crescenzo, R., Cigliano, L., Spagnuolo, M.S., Cancelliere, R., Gatto, C., Iossa, S., 2019. Early hepatic oxidative stress and mitochondrial changes following western diet in middle aged rats. Nutrients. 11, 2670.
• Newman, J.C., Covarrubias, A.J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., Verdin, E., 2017. Ketogenic diet reduces midlife mortality and improves memory in aging mice. Cell metabolism. 26, 547-557. e8.
• Norton, C.E., Jacobsen, N.L., Sinkler, S.Y., Manrique-Acevedo, C., Segal, S.S., 2020. Female sex and Western-style diet protect mouse resistance arteries during acute oxidative stress. American Journal of Physiology-Cell Physiology. 318, C627-C639.
• Parihar, A., Parihar, M.S., Milner, S., Bhat, S., 2008. Oxidative stress and anti-oxidative mobilization in burn injury. Burns. 34, 6-17.
• Parry, H.A., Kephart, W.C., Mumford, P.W., Romero, M.A., Mobley, C.B., Zhang, Y., Roberts, M.D., Kavazis, A.N., 2018. Ketogenic diet increases mitochondria volume in the liver and skeletal muscle without altering oxidative stress markers in rats. Heliyon. 4, e00975.
• Pinto, A., Bonucci, A., Maggi, E., Corsi, M., Businaro, R., 2018. Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease. Antioxidants. 7, 63.
• Suzuki, S., Toledo-Pereyra, L., Rodriguez, F., Cejalvo, D., 1993. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 55, 1265-1272.
• Ulloa-Padilla, J.P., Ghassibi, M.P., Dubovy, S.R., Kerr, D.A., 2020. Clinicopathologic Correlation of Kaposi Sarcoma Involving the Ocular Adnexa: Immunophenotyping of Diagnostic and Therapeutic Targets. Ophthalmic Plastic & Reconstructive Surgery. 36, 185-190.
• Vetrani, C., Costabile, G., Di Marino, L., Rivellese, A., 2013. Nutrition and oxidative stress: a systematic review of human studies. International journal of food sciences and nutrition. 64, 312-326.
• Wilson, C.R., Tran, M.K., Salazar, K.L., Young, M.E., Taegtmeyer, H., 2007. Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats. Biochemical Journal. 406, 457-467.
• Wright, C., Simone, N.L., 2016. Obesity and tumor growth: inflammation, immunity, and the role of a ketogenic diet. Current opinion in clinical nutrition and metabolic care. 19, 294-299.
• Wu, W., Tsuchida, H., Kato, T., Niwa, H., Horikawa, Y., Takeda, J., Iizuka, K., 2015. Fat and carbohydrate in western diet contribute differently to hepatic lipid accumulation. Biochemical and Biophysical Research Communications. 461, 681-686.