Protective effect of nanocurcumin against neurotoxicity induced by doxorubicin in rat’s brain

Khadrawy, Yasser A.; Hosny, Eman N; Mohammed, Haitham S.

doi:10.1016/j.neuro.2021.04.003

Cited by 14 publications

(7 citation statements)

References 56 publications

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“…Acetylcholinesterase (AchE) predominantly resides in cholinergic brain synapses, where it plays a crucial role in signal transduction and the regulation of acetylcholine (Ach) levels within cholinergic neurons [159]. In male mice, a note-worthy increase in AchE activity was observed in the DOX-treated group, corroborating the findings of [160,161], but contrasting with a recent study by [162], which reported DOX-induced inhibition of cortical AchE activities.…”

Section: Histological Features Of the Cerebral Cortexcontrasting

confidence: 75%

Impact of Virgin Coconut Oil and Carvedilol on Neurobehaviour, Apoptotic and Inflammatory Brain Markers in Doxorubicin Treated Mice

Chiamaka,

Uchechukwu,

Chioma

et al. 2023

PoS

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One of the significant side effects of doxorubicin treatment for cancer patients is cognitive impairment, and the mechanisms underlying this impairment must be investigated to treat or prevent it. The current study investigates the impact of virgin coconut oil and carvedilol administration on neurobehaviour brain apoptotic and inflammatory markers in doxorubicin-treated mice. 32 male and 32 female mice were randomly assigned to four groups of 8 animals each, and the treatment lasted for twenty-eight days. Group 1 animals in both the male and female groups were the controls. In comparison, the Group 2 animals in both groups received doxorubicin dosage (3.75 mg/kg body weight) intraperitoneally weekly as a single dose on days 5, 12, 19 and 26 to make up for the desired amount (15 mg/kg body weight). Group 3 animals received doxorubicin and were orally treated with virgin coconut oil (5ml/kg body weight) for 28 days. Group 4 animals received doxorubicin and were treated with carvedilol (5 mg/kg body weight) weekly for three days (days 5-7 for four weeks). The histological analysis of the brain tissue was done by staining the tissues with haematoxylin and eosin. The data was analyzed using GraphPad Prism 9.0. Analysis of Variance (ANOVA) was used to compare between groups. All results were presented as mean±SEM. Both virgin coconut oil and carvedilol demonstrated ameliorative effects on neurobehaviour and apoptotic and inflammatory brain markers.

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Section: Histological Features Of the Cerebral Cortexcontrasting

confidence: 75%

Impact of Virgin Coconut Oil and Carvedilol on Neurobehaviour, Apoptotic and Inflammatory Brain Markers in Doxorubicin Treated Mice

Chiamaka,

Uchechukwu,

Chioma

et al. 2023

PoS

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“…Indirect actions that have been suggested include the activation of several pathways that occur in various parts of the body resulting in the production of inflammatory mediators [ 8 ]. The over-production and dysregulation of inflammatory mediators are reported to take place due to the action of DOX on both cancerous as well on normal cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

et al. 2022

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Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The ‘nootropic-like’ activity could be related to diminished AChE and neuroinflammatory mediator levels.

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“…The current study showed that the oxidative stress and inflammatory state caused by administration of Dox were successfully down-regulated upon adding different doses (100, 300, and 500 mg/kg) of C. macrocarpa in a dose-dependent manner, and the lowest oxidative stress and pro-inflammatory state were shown in the group administering the highest dose of C. macrocarpa (Dox+ C.500 mg/kg (Figure 2a,c). Reducing levels of ROS and TNF-α are closely associated with reducing neurotoxicity, as mentioned in several recent studies [37,42]. Furthermore, the produced TNF-α by Dox can cross the blood-brain barrier and activate the microglia in the brain to release more TNF-α that elevates the production of nitric oxide by glia, leading to nitrosative and oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and neuronal apoptosis [5,43,44].…”

Section: Discussionmentioning

confidence: 92%

Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers

et al. 2021

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Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the C. macrocarpa leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the C. macrocarpa leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side effects.

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Protective effect of nanocurcumin against neurotoxicity induced by doxorubicin in rat’s brain

Cited by 14 publications

References 56 publications

Impact of Virgin Coconut Oil and Carvedilol on Neurobehaviour, Apoptotic and Inflammatory Brain Markers in Doxorubicin Treated Mice

Impact of Virgin Coconut Oil and Carvedilol on Neurobehaviour, Apoptotic and Inflammatory Brain Markers in Doxorubicin Treated Mice

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers

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