Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: Possible role of microglia inhibition

Bhardwaj, Manveen; Kumar, Anil

doi:10.1016/j.pharep.2016.07.005

Cited by 39 publications

(25 citation statements)

References 29 publications

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“…. This increase has also been reported in previous studies [39,40]. In the present study,the administration of CBZ by either route significantly decreased TNF-α content in the brain tissue as compared to the PTZ control group.…”

Section: Behavioral Assessment By Elevated Plus Maze Testsupporting

confidence: 92%

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

2019

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Objective: Carbamazepine (CBZ) is used as a first line in the treatment of grand mal and partial seizures, but it suffers from many side effects on different systems of the body. The objective of the present study was optimization of CBZ vesicular structures using 23 multifactorial design for the most efficient targeting of CBZ to the brain via the intranasal route. Methods: The concentration of CBZ (10 and 20%), type of vesicles (niosomes and spanlastics) and speed of rotation (200 and 300 rpm) were considered as the independent variables XA, XB and XC respectively, while the dependent variables were particle size PS (Y1), polydispersity index PDI (Y2), zeta potential ZP (Y3) and entrapment efficiency EE (Y4). The study of the effect of different formulation variables was carried out using Design-Expert ® software. CBZ-loaded spanlastics and noisome were prepared by the ethanol injection method and thin film hydration method, respectively. The optimized formulation was subjected to viscosity measurement, in vitro drug release and physical stability studies. In vivo evaluations in rats for the optimized formulation in comparison to oral CBZ suspension was carried out using behavioral assessment by elevated plus maze test, determination of endothelial nitric oxide synthase (e-NOS), reduced glutathione (GSH) and ELISA estimation of TNFα. Results: The selected optimized formulation (F0) containing 20% CBZ and spanlastic vesicular structure showed PS, PDI, ZP, and the EE % of 350.09 nm, 0.830, 16.124mV and 82.777%, respectively. In vitro release study of F0 demonstrated the ability of the F0 to increase drug release in the range time from 10-60 min (p<0.05) when compared with CBZ suspension. The viscosity of F0 was nearly uniform (65 cps). The photomicrograph taken by the transmission electron microscopy (TEM) reveals the spherical shape of F0. Good physical stability for six months of storage at 25˚ C was found for F0. The optimized spanlastic formulation F0 showed a decrease in latency time in behavior assessment test using elevated plus Maze test, a decrease in serum eNOS and TNF-α and increase in GSH when compared with the oral CBZ suspension, in addition to the histopathological study that revealed the more CBZ uptake by the brain. Conclusion: The optimized spanlastic formulation F0 achieved better results when compared with the oral CBZ suspension for targeting the CBZ spanlastics vesicular structure to the brain via the nasal route.

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Section: Behavioral Assessment By Elevated Plus Maze Testsupporting

confidence: 92%

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

2019

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“…Previous reports have demonstrated that CoQ10 prevents memory and cognitive deficits under different conditions [61-65]. The present findings indicate that CoQ10 can prevent the memory and cognitive impairment induced by DM.…”

Section: Discussionsupporting

confidence: 78%

Influence of Chronic Coenzyme Q10 Supplementation on Cognitive Function, Learning, and Memory in Healthy and Diabetic Middle-Aged Rats

2018

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Diabetes mellitus can induce impairment in learning and memory. Cognitive and memory deficits are common in older adults and especially in those with diabetes. This is mainly because of hyperglycemia, oxidative stress, and vascular abnormalities. Coenzyme Q10 (CoQ10) can decrease oxidative stress, hyperglycemia, and inflammatory markers, and improve vascular function. Therefore, the aim of the present study was to investigate the possible effects of CoQ10 on cognitive function, learning, and memory in middle-aged healthy and diabetic rats. Adult middle-aged male Wistar rats (390–460 g, 12–13 months old) were divided into 6 experimental groups. Diabetes was induced by a single i.p. injection of streptozotocin (60 mg/kg). CoQ10 (20 or 120 mg/kg, orally by gavage) was administered for 45 days. The cognitive function and learning memory of rats were evaluated using novel object recognition (NOR) and passive avoidance tests. The discrimination index of the NOR test in the diabetic groups receiving CoQ10 (20 or 120 mg/kg) and the healthy group receiving CoQ10 (120 mg/kg) was significantly higher than that in the control group. In addition, the step through latency was significantly longer and the time spent in the dark compartment was significantly shorter in the diabetic groups receiving CoQ10 than in the control group. CoQ10 supplementation can improve learning and memory deficits induced by diabetes in older subjects. In addition, CoQ10 at higher doses can improve cognitive performance in older healthy subjects.

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“…Furthermore, subcutaneous administration of DMSO in P7 C57/BL/6By mice is reported to induce microglial activation in the brain ( Saito et al, 2015 ) and administration of sub-toxic doses of paraquat in mice are reported to result in microglial activation prior to neurodegeneration ( Purisai et al, 2007 ). In addition, a microglial inhibitory mechanism has recently been proposed in CoQ10 mediated protection against Aβ(1–42) induced cognitive dysfunction ( Meneses et al, 2015 ) and pentylenetetrazol induced kindling epilepsy in mice ( Bhardwaj and Kumar, 2016 ). In addition, with accumulating evidence for the involvement of amyloid beta in glaucoma pathology ( Guo et al, 2007 , Ito et al, 2012 , Nizari et al, 2016 ) and growing recognition of mechanistic similarities between glaucoma and Alzheimer's disease ( Gupta et al, 2016 , Sivak, 2013 ), modulation of microglial activation by CoQ10 could contribute to the reported neuroprotective effects of this agent.…”

Section: Discussionmentioning

confidence: 99%

Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension

Davis¹,

Tian²,

Pahlitzsch³

et al. 2017

Mitochondrion

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Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α–tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p < 0.05) and Brn3 (p < 0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models.

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Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: Possible role of microglia inhibition

Abstract: The present study suggests the involvement of microglia inhibition in the protective effect of CoQ10 in PTZ induced kindling in mice.

Cited by 39 publications

References 29 publications

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

Influence of Chronic Coenzyme Q10 Supplementation on Cognitive Function, Learning, and Memory in Healthy and Diabetic Middle-Aged Rats

Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension

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