Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

Alrafiah, Aziza; Mehdar, Khlood M.

doi:10.1155/2021/5549638

Cited by 4 publications

(3 citation statements)

References 60 publications

(82 reference statements)

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“…; Sigma-Aldrich, St Louis, MO, USA). The seizures were classified according to the Racine Score (RC): 0, no-response; 1, myotonic jerks without rearing; 2, myoclonic jerks with rearing; 3, unilateral forelimb clonus; 4, rearing with bilateral forelimb clonus; and 5, generalized tonic-clonic seizure ( Al-Rafiah and Mehdar, 2021 ). If the RC score reached stage 5, we decided that epilepsy had been induced.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy

Arai

Kimura²,

Munakata

et al. 2022

Front. Neurosci.

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Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.

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Section: Methodsmentioning

confidence: 99%

Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy

Arai

Kimura²,

Munakata

et al. 2022

Front. Neurosci.

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“…Moreover, lutein cotreatment with antiepileptic drugs was recently reported to be a promising strategy either to improve therapeutic efficacy in patients suffering from epilepsy [15] or to improve cognitive function [16]. This compound has been additionally revealed to ameliorate either ischemia-reperfusion-induced vasculitic neuropathic pain and neuropathy in rats, or photoreceptor degeneration in a mouse model of retinitis pigmentosa [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid

Chuang

Chang

Cho

et al. 2022

IJMS

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Lutein (β,ε-carotene-3,3′-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plasmalemmal ionic currents occur in electrically excitable cells remain incompletely answered. The current hypothesis is that lutein produces any direct adjustments on ionic currents (e.g., hyperpolarization-activated cation current, Ih [or funny current, If]). In the present study, GH3-cell exposure to lutein resulted in a time-, state- and concentration-dependent reduction in Ih amplitude with an IC50 value of 4.1 μM. There was a hyperpolarizing shift along the voltage axis in the steady-state activation curve of Ih in the presence of this compound, despite being void of changes in the gating charge of the curve. Under continued exposure to lutein (3 μM), further addition of oxaliplatin (10 μM) or ivabradine (3 μM) could be effective at either reversing or further decreasing lutein-induced suppression of hyperpolarization-evoked Ih, respectively. The voltage-dependent anti-clockwise hysteresis of Ih responding to long-lasting inverted isosceles-triangular ramp concentration-dependently became diminished by adding this compound. However, the addition of 10 μM lutein caused a mild but significant suppression in the amplitude of erg-mediated or A-type K+ currents. Under current-clamp potential recordings, the sag potential evoked by long-lasting hyperpolarizing current stimulus was reduced under cell exposure to lutein. Altogether, findings from the current observations enabled us to reflect that during cell exposure to lutein used at pharmacologically achievable concentrations, lutein-perturbed inhibition of Ih would be an ionic mechanism underlying its changes in membrane excitability.

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“…Combinations of SVP and docosahexaenoic acid result in increased potency (3.6-fold) of SVP in pentylenetetrazol (PTZ) and kindling seizure models [ 10 ]. SVP and Lutein in combination showed a significant decline in seizure score in pilocarpine-induced epilepsy in rats [ 11 ]. SVP and TP427 in combination exhibited synergistic effects against epilepsy [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells

Pottoo

Salahuddin

Khan

et al. 2022

CIMB

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Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1β, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be −370.426 Kcal/mol, while the supramolecular ternary complex alone was −38.732 Kcal/mol, with a potential energy difference of −331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.

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Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

Cited by 4 publications

References 60 publications

Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy

Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy

Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells

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