Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems

Adisa, Rahmat Adetutu; Sulaimon, Lateef Adegboyega; Geraldine, Okeke Ebele; Ariyo, Olubukola Christianah; Abdulkareem, Fatimah B.

doi:10.1007/s43188-021-00105-1

Cited by 2 publications

(3 citation statements)

References 74 publications

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“…Митохондриальная дисфункция при ГКМП часто связана с повышенным окислительным стрессом, приводящим к повреждению митохондриальных компонентов и нарушению функции митохондрий. Антиоксиданты, такие как MitoQ или эламипретид* (SS-31), могут способствовать снижению окислительного стресса в митохондриях, защищают от повреждений и улучшают функцию митохондрий при ГКМП [84,85]. Метаболические модуляторы.…”

Section: A C C E P T E D F O R P U B L I C a T I O Nunclassified

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

Zhivodernikov,

Kirichenko,

Kozlova

et al. 2024

Morphology

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The pathomorphogenesis of hypertrophic cardiomyopathy is a disruption of the arrangement of bundles of muscle cells in the myocardium and is associated with mutations in genes encoding the synthesis of myocardial contractile proteins. Metabolic changes in this pathology are caused by hypertrophy of the interventricular septum due to disruption of the myocardial contractile apparatus associated with these mutations, as well as mitochondrial dysfunction. Mutations in myofiber proteins can negatively affect mitochondria through increased oxidative stress due to increased ATP demand. Mitochondria are complex organelles with their own circular DNA, as well as the presence of enzyme complexes involved in redox reactions, which causes frequent damage to mitochondrial protein structures and membranes by reactive oxygen species. In this regard, mitochondrial dysfunction can also be caused by mutations in genes encoding mitochondrial proteins, which leads to disruption of mitophagy and mitochondrial dynamics. The functioning of defective mitochondria is associated with insufficient ATP synthesis and ineffective muscle contraction, which leads to the same consequences at the tissue level as mutations in contractile protein genes. In this review, we tried to summarize the role of mitochondrial dysfunction in the pathomorphogenesis of hypertrophic cardiomyopathy.

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Section: A C C E P T E D F O R P U B L I C a T I O Nunclassified

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

Zhivodernikov,

Kirichenko,

Kozlova

et al. 2024

Morphology

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“…In the mitochondria MitoQ acts as an antioxidant and has demonstrated consistent benefits in oxidative stress – related diseases 14,15 and it is under investigation in many pathological conditions including liver diseases. Recently, we reported attenuation of HCC in Wistar rats by mitoQ 16 . Several studies have also reported SDH as activator of MitoQ in mitochondria 14 ; the ability of MitoQ to activate Nrf2 in disease settings has also been investigated 17,18 .…”

Section: Introductionmentioning

confidence: 98%

“…Recently, we reported attenuation of HCC in Wistar rats by mitoQ. 16 Several studies have also reported SDH as activator of MitoQ in mitochondria 14 ; the ability of MitoQ to activate Nrf2 in disease settings has also been investigated. 17,18 However, there is little or no information on putative binding modes of MitoQ to SDH and Nrf2/KEAP1 interactions.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanism of mitoquinol mesylate in mitigating the progression of hepatocellular carcinoma—in silico and in vivo studies

Sulaimon

Adisa

Samuel

et al. 2021

J of Cellular Biochemistry

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The safety and efficacy of mitoquinol mesylate (MitoQ) in attenuating the progression of hepatocellular carcinoma (HCC) in Wistar rats has been reported. However, the binding modes for MitoQ as well as its molecular mechanisms in cirrhosis and liver cancer have not been fully investigated. This study sought to understand the structural and molecular mechanisms of MitoQ in modulating the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and mitochondrial succinate dehydrogenase (SDH) in cirrhotic‐HCC rats. The research indicates that the upregulated Nrf2 expression in cirrhotic‐HCC rats was significantly (p < 0.05) reduced by MitoQ while the activity of SDH was significantly (p < 0.05) increased. Analysis of binding modes revealed MitoQ interacts with amino acid residues in the active pocket of tramtrack and bric‐a‐brac (BTB) and KELCH domains of KEAP1 with average binding affinities of −66.46 and −74.74 kcal/mol, respectively. Also, MitoQ interacted with the key amino acid residues at the active site of mitochondrial complex II with a higher average binding affinity of −75.76 kcal/mol compared to co‐crystallized ligand of complex II (−62.31 kcal/mol). Molecular dynamics simulations data showed the binding of MitoQ to be stable with low eigenvalues while the quantum mechanics calculations suggest MitoQ to be very reactive with its mechanism of chemical reactivity to be via electrophilic reactions. Thus, MitoQ modulates expression of Nrf2 and enhances activity of mitochondrial SDH in cirrhotic‐HCC rats via its interaction with key amino acid residues in the active pocket of BTB and KELCH domains of KEAP1 as well as amino residues at the active site of SDH. These findings are significant in demonstrating the potential of Nrf2 and SDH as possible biomarkers for the diagnosis and/or prognosis of hepatocellular carcinoma in patients. This study also supports repurposing of mitoQ for the treatment/management of liver cirrhosis and HCC.

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Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems

Cited by 2 publications

References 74 publications

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

Molecular mechanism of mitoquinol mesylate in mitigating the progression of hepatocellular carcinoma—in silico and in vivo studies

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