Potential Protective Effect of Coenzyme Q10 on Doxorubicin-Induced Neurotoxicity and Behavioral Disturbances in Rats

Okudan, Nilsel; Belviranlı, Muaz; Sezer, Tuğba

doi:10.1007/s11064-021-03522-8

Cited by 11 publications

(3 citation statements)

References 62 publications

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“…Further, MDA is a byproduct of polyunsaturated fatty acid peroxidation and is considered a key marker of LOP [37]. Furthermore, four doses of peripheral DOX injections led to an increase in MDA levels in the brain tissues in the current data, which were also validated by other studies [5,38]. By reducing MDA levels, QUET (20 mg/kg, p.o.)…”

Section: Discussionsupporting

confidence: 83%

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis

Mani,

Alshammeri

2023

IJMS

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Chemotherapy is considered a major choice in cancer treatment. Unfortunately, several cognitive deficiencies and psychiatric complications have been reported in patients with cancer during treatment and for the rest of their lives. Doxorubicin (DOX) plays an important role in chemotherapy regimens but affects both the central and peripheral nervous systems. Antipsychotic drugs alleviate the behavioral symptoms of aging-related dementia, and the atypical class, quetiapine (QUET), has been shown to have beneficial effects on various cognitive impairments. The present investigation aimed to determine the possible mechanism underlying the effect of thirty-day administrations of QUET (10 or 20 mg/kg, p.o.) on DOX-induced cognitive deficits (DICDs). DICDs were achieved through four doses of DOX (2 mg/kg, i.p.) at an interval of seven days during drug treatment. Elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks were performed to confirm the DICDs and find the impact of QUET on them. The ELISA tests were executed with oxidative [malondialdehyde (MDA), catalase, and reduced glutathione (GSH)], inflammatory [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α)], and apoptosis [B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein (Bax), and Caspase-3] markers were assessed in the brain homogenate to explore the related mechanisms. DICD lengthened the transfer latency time in EPM, shortened the exploration time of the novel object, reduced the discrimination ability of the objects in NOR, and lowered the number of arm entries and time spent in the novel arm. QUET alleviated DICD-related symptoms. In addition, QUET reduced neuronal oxidative stress by reducing MDA and elevating GSH levels in the rat brain. Moreover, it reduced neuronal inflammation by controlling the levels of COX-2, NF-κB, and TNF-α. By improving the Bcl-2 level and reducing both Bax and Caspase-3 levels, it protected against neuronal apoptosis. Collectively, our results supported that QUET may protect against DICD, which could be explained by the inhibition of neuronal inflammation and the attenuation of cellular apoptosis protecting against oxidative stress.

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Section: Discussionsupporting

confidence: 83%

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis

Mani,

Alshammeri

2023

IJMS

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“…(22) It has been reported that some of the components of Twendee X are effective in preventing migraine and anxietylike behavior. (23) Several lines of evidence have demonstrated that oxidative stress is related to anxiety, (24) and vitamin E deficiency increases anxious behavior in rodent models. (25) Because mice in the Twendee X-treated group were better at learning the platform location compared to the mice in the untreated group, the former presumably were better able to assess and respond to this situation.…”

Section: Twendee X Improves Vitamin E-deficiency-induced Cogni-mentioning

confidence: 99%

Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice

Fukui

You

Kato

et al. 2023

J. Clin. Biochem. Nutr.

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“…Paclitaxel-induced neurotoxicity has been reported to be suppressed by the addition of antioxidants (such as docosahexaenoic acid, acetyl-L-carnitine hydrochloride, N -acetyl-L-cysteine, and sodium ascorbate) in cultured cells [ 31 ]. Also, in animal studies in rats, DOX-induced neurotoxicity and behavior were potentially protected by coenzyme Q10 [ 32 ], and DOX-induced cardiotoxicity is significantly suppressed with candesartan and quercetin [ 33 ]. For Compound A , we plan to search for drugs that alleviate the neurotoxicity and enhance the toxicity to OSCC.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

et al. 2023

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Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

show abstract

Potential Protective Effect of Coenzyme Q10 on Doxorubicin-Induced Neurotoxicity and Behavioral Disturbances in Rats

Cited by 11 publications

References 62 publications

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis

Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

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