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Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

Abstract The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This antiseizure property is probably mediated through GABAergic receptors (PTZ effect) and blockade of membrane bound KATP channels (AP effect) with some enhancement by serum ketosis.
PMID
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Authors

Mayor MeshTerms

4-Aminopyridine

Animal Nutritional Physiological Phenomena

Diet, Carbohydrate-Restricted

Ketogenic Diet

Pentylenetetrazole

Strychnine

Keywords
Journal Title nigerian journal of physiological sciences : official publication of the physiological society of nigeria
Publication Year Start




PMID- 28262846
OWN - NLM
STAT- MEDLINE
DA  - 20170306
DCOM- 20170315
LR  - 20170315
IS  - 0794-859X (Print)
IS  - 0794-859X (Linking)
VI  - 31
IP  - 2
DP  - 2017 Mar 06
TI  - Antiseizure Effects of Ketogenic Diet on Seizures Induced with
      Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.
PG  - 115-119
AB  - The ketogenic diet (KD) is a cheap and effective alternative therapy for most
      epilepsy. There are paucity of experimental data in Nigeria on the usefulness of 
      KD in epilepsy models. This is likely to be responsible for the poor clinical
      acceptability of the diet in the country. This study therefore aimed at providing
      experimental data on usefulness of KD on seizure models. The study used 64 Wistar
      rats that were divided into two dietary groups [normal diet (ND) and ketogenic
      diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride
      ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal
      rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual
      rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ),
      4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and
      serum chemistry were determined and seizure parameters recorded. Serum ketosis
      was significantly higher in MCT-KD-fed rats (12.7 +/-2.6) than ND-fed
      (5.17+/-0.86) rats. Fasting blood glucose was higher in ND-fed rats
      (5.3+/-0.9mMol/l) than in MCT-KD fed rats (5.1+/-0.5mMol/l) with p=0.9. Seizure
      latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after
      PTZ-induced seizures (61+/-9sec vs 570+/-34sec) and AP-induced seizures
      (49+/-11sec vs 483+/-41sec). The difference after Str-induced seizure (51+/-7 vs 
      62+/-8 sec) was not significan. The differences in seizure duration between
      ND-fed and MCT-KD fed rats with PTZ (4296+/-77sec vs 366+/-46sec) and with AP
      (5238+/-102sec vs 480+/-67sec) were significant (p&lt;0.05), but not with STR
      (3841+/-94sec vs 3510+/-89sec) respectively. The mean serum Na+ was significantly
      higher in MCT-KD fed (141.7+/-2.1mMol/l) than ND-fed rats (137+/-2.3mMol/l).
      There was no significant difference in mean values of other serum electrolytes
      between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to
      PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This
      antiseizure property is probably mediated through GABAergic receptors (PTZ
      effect) and blockade of membrane bound KATP channels (AP effect) with some
      enhancement by serum ketosis.
FAU - Sanya, E O
AU  - Sanya EO
AD  - Department of Medicine, University of Ilorin, Ilorin. emanuelosanya@yahoo.com.
FAU - Soladoye, A O
AU  - Soladoye AO
FAU - Desalu, O O
AU  - Desalu OO
FAU - Kolo, P M
AU  - Kolo PM
FAU - Olatunji, L A
AU  - Olatunji LA
FAU - Olarinoye, J K
AU  - Olarinoye JK
LA  - eng
PT  - Journal Article
DEP - 20170306
PL  - Nigeria
TA  - Niger J Physiol Sci
JT  - Nigerian journal of physiological sciences : official publication of the
      Physiological Society of Nigeria
JID - 8811109
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Plant Oils)
RN  - 3W1JG795YI (sunflower seed oil)
RN  - 9NEZ333N27 (Sodium)
RN  - BH3B64OKL9 (4-Aminopyridine)
RN  - H9Y79VD43J (Strychnine)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - *4-Aminopyridine
MH  - *Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - Biomarkers/blood
MH  - Blood Glucose/metabolism
MH  - *Diet, Carbohydrate-Restricted
MH  - Disease Models, Animal
MH  - *Ketogenic Diet
MH  - Ketosis
MH  - Male
MH  - *Pentylenetetrazole
MH  - Plant Oils/*administration &amp; dosage
MH  - Rats, Wistar
MH  - Reaction Time
MH  - Seizures/blood/chemically induced/physiopathology/*prevention &amp; control
MH  - Sodium/blood
MH  - *Strychnine
MH  - Time Factors
EDAT- 2017/03/07 06:00
MHDA- 2017/03/16 06:00
CRDT- 2017/03/07 06:00
PHST- 2017/03/06 [received]
PHST- 2017/03/06 [accepted]
PST - epublish
SO  - Niger J Physiol Sci. 2017 Mar 6;31(2):115-119.

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