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Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats.

ABSTRACT: Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity may be modulated by A₁ type adenosine receptors (A₁Rs). The first aim was to determine whether intraperitoneal (i.p.) administration of a specific A₁R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 0.2 mg/kg) and a selective adenosine A_2A receptor antagonist (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine) (SCH 58261; 0.5 mg/kg) have a modulatory influence on i.p. 1000 mg/kg uridine-evoked effects on SWD number in WAG/Rij rats. The second aim was to assess efficacy of a sub-effective dose of uridine (i.p. 250 mg/kg) combined with beta-hydroxybutyrate salt + medium chain triglyceride (KSMCT; 2.5 g/kg, gavage) on absence epilepsy. DPCPX completely abolished the i.p. 1000 mg/kg uridine-evoked alleviating effect on SWD number whereas SCH 58261 was ineffective, confirming the A₁R mechanism. Moreover, the sub-effective dose of uridine markedly enhanced the effect of KSMCT (2.5 g/kg, gavage) on absence epileptic activity. These results demonstrate the anti-epilepsy benefits of co-administrating uridine and exogenous ketone supplements as a means to treat absence epilepsy.

SUBMITTER: Brunner B

PROVIDER: S-EPMC7830695 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats.

Brunner Brigitta B Rauch Enikő E Ari Csilla C D'Agostino Dominic P DP Kovács Zsolt Z

Nutrients 20210115 1

Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity may be modulated by A1 type adenosine receptors (A1Rs). The first aim was to determine whether intraperitoneal (i.p.) administration of a specific A1R antagonist 1, ...[more]

PMID: 33467454

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Project description:It has been demonstrated previously that exogenous ketone supplements such as ketone ester (KE) decreased absence epileptic activity in a well-studied animal model of human absence epilepsy, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It is known that lipopolysaccharide (LPS)-generated changes in inflammatory processes increase absence epileptic activity, while previous studies show that ketone supplement-evoked ketosis can modulate inflammatory processes. Thus, we investigated in the present study whether administration of exogenous ketone supplements, which were mixed with standard rodent chow (containing 10% KE + 10% ketone salt/KS, % by weight, KEKS) for 10 days, can modulate the LPS-evoked changes in absence epileptic activity in WAG/Rij rats. At first, KEKS food alone was administered and changes in spike-wave discharge (SWD) number, SWD time, discharge frequency within SWDs, blood glucose, and beta-hydroxybutyrate (?HB) levels, as well as body weight and sleep-waking stages were measured. In a separate experiment, intraperitoneal (i.p.) injection of LPS (50 ?g/kg) alone and a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) alone, as well as combined IP injection of indomethacin with LPS (indomethacin + LPS) were applied in WAG/Rij rats to elucidate their influences on SWD number. In order to determine whether KEKS food can modify the LPS-evoked changes in SWD number, KEKS food in combination with IP LPS (50 ?g/kg) (KEKS + LPS), as well as KEKS food with IP indomethacin (10 mg/kg) and LPS (50 ?g/kg) (KEKS + indomethacin + LPS) were also administered. We demonstrated that KEKS food significantly increased blood ?HB levels and decreased not only the spontaneously generated absence epileptic activity (SWD number), but also the LPS-evoked increase in SWD number in WAG/Rij rats. Our results suggest that administration of exogenous ketone supplements (ketogenic foods) may be a promising therapeutic tool in the treatment of epilepsy.

Project description:Mushrooms are nutritious foods that are widely cultivated all over the world. They are rich in a range of compounds linked to improving functions of the immune system including carotenoids, alkaloids, lectins, enzymes, folates, fats, organic acids, minerals, polysaccharides, phenolics, proteins, tocopherols, terpenoids, and volatile compounds. In this study we investigated, the immunomodulatory activity in rats of the aqueous extracts of five of the most common edible mushrooms belonging to Family Basidiomycota-white-rot fungi including, Lentinula edodes, Agaricus bisporus, Pleurotus ostreatus, Pleurotus columbinus, and Pleurotus sajor-caju. Male Wistar albino rats were assigned to thirteen groups and Immunosuppression was induced by oral administration of dexamethasone (0.1 mg/kg), followed by oral administration of the mushroom extracts at low (200 mg/kg) and high (400 mg/kg) doses. A positive control group received the immune stimulant Echinacea extract Immulant® at (30 mg/kg), while the negative control group received only saline. From each animal, in each group, blood samples were collected after 15 days for complete blood counts and for measurement of immunologic parameters, including lysozyme activity, nitric oxide (NO) production and serum cytokines including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin 1 beta (IL-1β) levels. Results have shown that white blood cells (WBCs) and lymphocytic counts were significantly boosted by high doses of each of the five mushroom extracts (207-289% increase for WBC and 153-175% for lymphocytes) with a significant increase in lysozyme activity (110-136% increase), NO concentration (159-232% increase) and cytokines as compared to the negative control group. Histopathological examination of the rats' spleen and thymus tissues has shown marked lymphocytic proliferation that was more obvious at the higher doses. In conclusion, our results showed that the five edible mushroom extracts revealed significant immunostimulatory effects preclinically particularly, at the higher doses (400 mg/kg) which can be considered the effective dose.

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Dataset Information

Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats.

Publications

Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats.

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