Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat

Aktaş, Zeynep; Cansu, Ali; Erdoğan, Deniz; Take, Gülnur; Goktas, Guleser; Özdek, Şengül; Serdaroğlu, Ayşe

doi:10.1016/j.seizure.2009.02.003

Cited by 23 publications

(8 citation statements)

References 19 publications

(41 reference statements)

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“…This observation of mild cell toxicity induced by OX is in agreement with previous finding [40,82] that showed OX as an agent that can cause anatomic and organizational disruption in cell layers, nuclear shrinkage, and cell atrophy. Conclusively, these findings would add to our previous finding that emulsomes can shield OX cell damaging effects [40] the ability of G16 emulsomal thermogel composite to further protect nasal cells from the severe effect of OX.…”

Section: Resultssupporting

confidence: 93%

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

et al. 2018

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The use of nanocarrier delivery systems for direct nose to brain drug delivery shows promise for achieving increased brain drug levels as compared to simple solution systems. An example of such nanocarriers is emulsomes formed from lipid cores surrounded and stabilised by a corona of phospholipids (PC) and a coating of Tween 80, which combines the properties of both liposomes and emulsions. Oxcarbazepine (OX), an antiepileptic drug, was entrapped in emulsomes and then localized in a poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer thermogel. The incorporation of OX emulsomes in thermogels retarded drug release and increased its residence time (MRT) in rats. The OX-emulsome and the OX-emulsome-thermogel formulations showed in vitro sustained drug release of 81.1 and 53.5%, respectively, over a period of 24 h. The pharmacokinetic studies in rats showed transport of OX to the systemic circulation after nasal administration with a higher uptake in the brain tissue in case of OX-emulsomes and highest MRT for OX-emulsomal-thermogels as compared to the IN OX-emulsomes, OX-solution and Trileptal® suspension. Histopathological examination of nasal tissues showed a mild vascular congestion and moderate inflammatory changes around congested vessels compared to saline control, but lower toxic effect than that reported in case of the drug solution.

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Section: Resultssupporting

confidence: 93%

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

et al. 2018

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“…However, no significant differences were found between groups. 10,41 Aktas et al 42 studied the histopathologic changes in vivo in retina ganglion cell layer induced by VPA and OXC and found that VPA causes RGC atrophy without significant RGC loss whereas OXC treatment led significant negative effects on the structure and number of the RGCs and concluded that the color vision deficits due to VPA may be related with ganglion cell loss; the study was an in vivo study and degree of the toxicity was associated with the duration of the treatment and the dose of the antiepileptic drug, and the doses applied in vivo were not directly related to the doses used in humans.…”

Section: Discussionmentioning

confidence: 99%

Optical coherence tomography and neurodegeneration in epilepsy

Bilen

Titiz

Bilen

et al. 2019

European Journal of Ophthalmology

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Purpose: To compare optical coherence tomography measurements; central macular thickness, ganglion cell complex, and retinal nerve fiber layer thickness in patients with epilepsy versus healthy controls. Methods: We evaluated 28 eyes of 28 patients with epilepsy and 34 eyes of 34 healthy subjects. Central macular thickness, ganglion cell complex, and retinal nerve fiber layer thickness measurements were performed by spectral-domain optical coherence tomography. Results: Superior and superotemporal quadrant ganglion cell complex, average, and superior quadrant retinal nerve fiber layer thickness measurements were significantly lower in epilepsy group compared to healthy control subjects. Central macular thickness was significantly lower in polytherapy group compared to monotherapy group. Ganglion cell complex and retinal nerve fiber layer thickness measurements were not significantly different between polytherapy and monotherapy groups. Conclusion: The present study shows that epileptic patients taking antiepileptic drugs have reduced ganglion cell complex and retinal nerve fiber layer thickness compared to healthy controls. This can be related to the epileptic process in the brain. Optical coherence tomography may be a useful tool for showing the neurodegeneration in patients with epilepsy.

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“…53 In accordance with our results, VPA treatment per se had no effect on RGC number even after 90 days of VPA treatment. 54 If VPA will be considered in future for the treatment of a chronic retinal neurodegenerative disease such as glaucoma, possible effects of VPA on retinal function have to be monitored carefully.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid–Mediated Neuroprotection and Regeneration in Injured Retinal Ganglion Cells

Biermann¹,

Grieshaber²,

Goebel

et al. 2010

Invest. Ophthalmol. Vis. Sci.

109

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Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat

Abstract: OXC seems to be toxic to RGCs at 100mg/kg dose when it is been given as a monotherapy or combined with VPA. Single VPA treatment has no effect on RGC number.

Cited by 23 publications

References 19 publications

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

Optical coherence tomography and neurodegeneration in epilepsy

Valproic Acid–Mediated Neuroprotection and Regeneration in Injured Retinal Ganglion Cells

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