Effects of valproate acid on blood lipid, serum leptin and cerebral cortex in juvenile and adult rat

LI Jing; LI Dan; HUANG Shao-Ping

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Chinese Journal of Contemporary Pediatrics ›› 2010, Vol. 12 ›› Issue (06) : 479-482.

EXPERIMENTAL RESEARCH

Effects of valproate acid on blood lipid, serum leptin and cerebral cortex in juvenile and adult rat

LI Jing, LI Dan, HUANG Shao-Ping

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Abstract

OBJECTIVE: To study the effects of valproate acid (VPA) on serum lipid and leptin levels and cerebral cortex in juvenile and adult rats. METHODS: Twenty healthy juvenile female Sprague-Dawley (SD) rats (21-day-old) and twenty healthy adult female SD rats (2-month-old) were randomly divided into four groups (n=10 each): juvenile control, juvenile VPA, adult control and adult VPA. Juvenile and adult VPA groups were fed with VPA 200 mg/kg daily, while the two control groups were fed with normal saline. The body weights were recorded weekly. Six weeks after feeding, serum and brain samples were obtained. Serum lipid levels including total cholesterol (TC), triglycerides (TG) and lower density lipoprotein cholesterol (LDL-C) were determined. Serum leptin (LEP) levels were measured by radioimmunoassay (RIA). Myelin staining and Nissl staining were used to evaluate the changes of brain tissues. RESULTS: The weight and serum LEP and lipid levels in both juvenile and adult VPA groups increased significantly compared with those in the control groups (P<0.05). The juvenile VPA group had more increased serum LEP and lipid levels than the adult VPA group (P<0.05). The Myelin staining showed that the average fiber density in the VPA groups was significantly lower than that in the control groups (P<0.05). The Nissl staining showed that the number of toluidine blue staining neurons in the VPA groups was not statistically different from the control groups. CONCLUSIONS: VPA may increase serum LEP and lipid levels in both juvenile and adult rats, and more increased levels may be found in juvenile rats. Longterm VPA treatment may have an adverse effect on brain myelination, but no effect on neurons.［Chin J Contemp Pediatr, 2010, 12 (6):479-482］

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Valproate / Leptin / Blood lipid / Cerebral coxtex / Rats

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LI Jing, LI Dan, HUANG Shao-Ping. Effects of valproate acid on blood lipid, serum leptin and cerebral cortex in juvenile and adult rat[J]. Chinese Journal of Contemporary Pediatrics. 2010, 12(06): 479-482

References

［1］Hamed SA, Fida NM, Hamed EA. States of serum leptin and insulin in children with epilepsy: risk predictors of weight gain［J］.Europ J Paediatr Neurol, 2009, 13(3):261-268.
［2］Hamed SA. Leptin and insulin homeostasis in epilepsy: Relation to weight adverse conditions［J］. Epilepsy Res, 2007, 75(1):1-9.
［3］Hamed SA, Hamed EA, Kandil MR, El-Shereef HK, Abdellah MM, Omar H. Serum thyroid hormone balance and lipid profile in patients with epilepsy［J］. Epilepsy Res, 2005, 66(1-3):173-183.
［4］El-Khatib F, Rauchenzauner M, Lechleitner M, Hoppichler F, Naser A, Waldmann M, et al. Valproate, weight gain and carbohydrate craving: A gender study［J］. Seizure, 2007, 16(3):226-232.
［5］Sobaniec-Lotowska ME. A transmission electron microscopic study of microglia/macrophages in the hippocampal cortex and neocortex following chronic exposure to valproate［J］. Int J Exp Pathol, 2005, 86(2):91-96.
［6］Shao L. Young LT, Wang JF. Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells［J］.Biol Psychiatry, 2005, 58(11):1879-1884.
［7］Biton V. Effect of antiepileptic drugs on body weight: overview and clinical implications for the treatment for the treatment of epilepsy［J］. CNS Drugs, 2003, 17(11):781-791.
［8］Zimmermanu U, Kraus T, Himmerich H, Schuld A, Pollmacher T. Epidemiology, implications and mechanisms underlying drug induced weight gain psychiatric patients［J］. Psychiatr Res, 2003, 37(3):193-220.
［9］van den Pol AN. Weighing the role of hypothalamic feeding neurotransmitters［J］. Neuron, 2003, 40(6):1059-1061.
［10］Sahu A. A hypothalamic role in energy balance with special emphasis on leptin. Minireview［J］. Endocrinology, 2004, 145(6):2613-2620.
［11］Luef GL, Lechleitner M, Bauer G, Trinka E, Hengster P. Valproic acid modulates islet cell insulin secretion: a possible mechanisms of weight gain in epilepsy patients［J］. Epilepsy Res, 2003, 55(1-2):53-58.
［12］Mctigue K, Larson JC, Valoski A, Burke G. Kotchen J, Lewis, C.E, et al. Mortality and cardiac and vascular outcomes in extremely obese women［J］. JAMA, 2007, 296(1):79-86.
［13］Sonmez FM , Demir E, Orem A, Yildirmis S, Orhan F, Aslan A, et al. Effect of Antiepileptic drugs on plasma lipids, lipoprotein, liver onzymes［J］. Child Neurol, 2006, 21(1):70-74.
［14］Luef M, Rauchenzauner M, Waldmann W, Sturm A, Sandhofer K, Seppi E, et al. Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment［J］. Epilepsy Research, 2009, 86(1):42-47.
［15］Pylvanen V, Pakarinen A, Knip M, Isojarvi J. Insulin-related metabolic changes during treatment with valproate in patients with epilepsy［J］. Epilepsy Behavior, 2006, 8(3):643-648.
［16］Spiegel A, Nabel E, Volkow N, Landis S, Li TK. Obesity on the brain［J］. Nat Neurosci, 2005, 8(5):552-553.
［17］Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J. Valproate-induced hyperammonemic encephalopathy［J］. Acta Neurol Scand, 2006, 114(1):1-7.
［18］Nathan BP, Nisar R, Short J, Randall S, Grissom E, Griffin G, et al. Delayed olfactory nerve regeneration in ApoE-deficient mice［J］. Brain Res, 2005, 1041(1):87-94.
［19］Bazinet RP, Rao JS, Chang L, Rapoport SI, Lee HJ. Chronic valproate does not alter the kinetics of docosahexaenoic acid within brain phospholipids of the unanesthetized rat［J］. Psychopharmacology (Berl), 2005,182(1):180-185.
［20］Reid PC, Lin S, Vanier MT, Ohno-Iwashita Y, Harwood HJ Jr, Hickey WF, et al. Partial blockage of sterol biosynthesis with a squalene synthase inhibitor in early postnatal Niemann-Pick type C npcnih null mice brains reduces neuronal cholesterol accumulation, abrogates astrogliosis, but may inhibit myelin maturation［J］. J Neurosci Methods, 2008, 168(1):15-25.