Untitled

Abstract

Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

“…Conversely, in a hypoglycemic in vivo model, ( d or l )-βOHB, but not AcAc prevented hippocampal lipid peroxidation (Haces et al, 2008; Maalouf et al, 2007; Marosi et al, 2016; Murphy, 2009; Tieu et al, 2003). In vivo studies of mice fed a ketogenic diet (87% kcal fat and 13% protein) exhibited neuroanatomical variation of antioxidant capacity (Ziegler et al, 2003), where the most profound changes were observed in hippocampus, with increase glutathione peroxidase and total antioxidant capacities.…”

“…Taken together, most reports link βOHB to attenuation of oxidative stress, as its administration inhibits ROS/superoxide production, prevents lipid peroxidation and protein oxidation, increases antioxidant protein levels, and improves mitochondrial respiration and ATP production (Abdelmegeed et al, 2004; Haces et al, 2008; Jain et al, 1998; Jain et al, 2002; Kanikarla-Marie and Jain, 2015; Maalouf et al, 2007; Maalouf and Rho, 2008; Marosi et al, 2016; Tieu et al, 2003; Yin et al, 2016; Ziegler et al, 2003). While AcAc has been more directly correlated than βOHB with the induction of oxidative stress, these effects are not always easily dissected from prospective pro-inflammatory responses (Jain et al, 2002; Kanikarla-Marie and Jain, 2015; Kanikarla-Marie and Jain, 2016).…”

Mitochondria, oxidative stress, and temporal lobe epilepsy

“…A role for mitochondrial bioenergetics has also been suggested to underlie the protective effects of the KD. For example, the KD has been shown to produce mitochondrial biogenesis (Bough et al, 2006), a decrease in mitochondrial ROS (Maalouf et al, 2007) due to upregulation of the uncoupling protein UCP2 (Sullivan et al, 2004), increase the cellular antioxidant capacity (Ziegler et al, 2003; Costello and Delanty, 2004; Nazarewicz et al, 2007), and in vitro studies have demonstrated that ketosis byproducts have the ability to prevent mtDNA deletions and cell death (Yamamoto and Mohanan, 2003; Santra et al, 2004). The KD has recently been demonstrated to improve the mitochondrial redox status in rats fed the diet for 3 weeks, which may improve the ability of the brain to resist metabolic changes and oxidative stress which partly underlies the occurrence of seizures (Jarrett et al, 2008b).…”

Clinical review: Ketones and brain injury

“…Ketones can oxidize coenzyme Q, thus decreasing mitochondrial free radical formation. Additionally, the reduction of NAD favors reduction of glutathione, which ultimately favors destruction of hydrogen peroxide by glutathione peroxidase reaction [46,47]. …”