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

Year 2022, Volume: 39 Issue: 1, 313 - 313, 01.01.2022

Songül Doğanay Özcan Budak Nurten Bahtiyar Veysel Toprak

Abstract

In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue. 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 four weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods. 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). 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. Clin. Cancer Res. 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. J. Nutr. Biochem. 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. Curr. Opin. Neurol. 30, 187.
• Buege, J., Aust, S., 1978. Microsomal lipid peroxidation. Methods Enzymol. 52, 302–310.
• Fleet, J.C., 2014. Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 307, G249-G259.
• Freeman, J.M., Kossoff, E.H., 2010. Ketosis and the ketogenic diet, advances in treating epilepsy and other disorders. Adv. Pediatr. 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. J. Cereb. Blood Flow. Metab. 36, 1603-1613.
• Hariharan, D., Vellanki, K., Kramer, H., 2015. The Western diet and chronic kidney disease. Curr. Hypertens. Rep. 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. J. Lipid Res. 51, 1380-1393.
• 14. 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 Cancer. 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. J. Neurochem. 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 Arch. Pharmacol. 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. Nat. Rev. Immunol. 17, 306-321.
• Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 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. Neurosci. Lett. 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 Metab. 26, 547-557.
• 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. Am. J. Physiol. Cell Physiol. 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. Plast. Reconstr. Surg. 36, 185-190.
• Vetrani, C., Costabile, G., Di Marino, L., Rivellese, A., 2013. Nutrition and oxidative stress: A systematic review of human studies. Int. J. Food Sci. Nutr. 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. Biochem. J. 406, 457- 467.
• Wright, C., Simone, N.L., 2016. Obesity and tumor growth: inflammation, immunity, and the role of a ketogenic diet. Curr. Opin. Clin. Nutr. Metab. 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. Biochem. Biophys. Res. Commun. 461, 681-686.