Mitochondria-targeted antioxidant, mito-TEMPO mitigates initiation phase of N-Nitrosodiethylamine-induced hepatocarcinogenesis

Shetty, Shricharith; Anushree, U; Kumar, Rajesh; Bharati, Sanjay

doi:10.1016/j.mito.2021.03.001

Cited by 14 publications

(10 citation statements)

References 52 publications

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“…Optical density of the sample was read at excitation wavelength 500 nm and emission wavelength 520 nm in fluorimeter (FP8300, Jasco, USA). Further, activities of mitochondrial complex-I, complex-II, and complex-IV, malate dehydrogenase (MDH) and isocitrate dehydrogenase (IDH) in cardiac tissue were estimated according to the procedure described previously [ 19 – 21 ].…”

Section: Methodsmentioning

confidence: 99%

Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity

Tambe

Aranjani

Bharati

2023

Cancer Chemother Pharmacol

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Purpose The mitochondria-targeted antioxidants (MTAs) are known to offer protection against mitochondrial oxidative stress. The recent evidences support their role in mitigating oxidative stress-induced diseases, including cancer. Therefore, this study investigated cardioprotective potential of mito-TEMPO against 5-FU-induced cardiotoxicity. Methods Mito-TEMPO was administered to male BALB/C mice (intraperitoneally, 0.1 mg/kg b.w. for 7 days) followed by intraperitoneal administration of 5- FU (12 mg/kg b.w. for 4 days). During this period, mito-TEMPO treatment was also continued. The cardioprotective potential of mito-TEMPO was assessed by evaluating cardiac injury markers, extent of non-viable myocardium and histopathological alterations. Mitochondrial functional status and mitochondrial oxidative stress were assessed in cardiac tissue. 8-OHdG expression and apoptotic cell death were assessed using immunohistochemical techniques. Results The level of cardiac injury markers CK-MB and AST were significantly (P ≤ 0.05) decreased in mito-TEMPO pre-protected group which was further reflected in histopathology as decrease in the percentage of non-viable myocardial tissue, disorganization, and loss of myofibrils. Mito-TEMPO ameliorated mtROS, mtLPO and conserved mitochondrial membrane potential. Further, it had significantly (P ≤ 0.05) improved the activity of mitochondrial complexes and mitochondrial enzymes. A significant (P ≤ 0.05) increase in the level of mtGSH, activity of mitochondrial glutathione reductase, glutathione peroxidase, and mitochondrial superoxide dismutase was observed. A decreased expression of 8-OHdG and reduced apoptotic cell death were observed in mito-TEMPO pre-protected group. Conclusion Mito-TEMPO effectively mitigated 5-FU-induced cardiotoxicity by modulating mitochondrial oxidative stress, hence may serve as a protective agent/adjuvant in 5-FU-based combinatorial chemotherapy.

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Section: Methodsmentioning

confidence: 99%

Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity

Tambe

Aranjani

Bharati

2023

Cancer Chemother Pharmacol

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“…Mitochondrial dysfunction promotes the accumulation of ROS, mtDNA damage and proto-oncogene activation, which are associated with the induction and progression of HCC [ 426 , 427 ]. A reduction in the mitochondrial membrane permeability (MMP) inhibits the apoptosis of HCC cells [ 428 ].…”

Section: Interplay Between Apoptosis and Autophagymentioning

confidence: 99%

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

2023

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The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways that are critical for cell survival or death. The balance between apoptosis and autophagy regulates liver cell turnover and maintains intracellular homeostasis. However, the balance is often dysregulated in many cancers, including HCC. Autophagy and apoptosis pathways may be either independent or parallel or one may influence the other. Autophagy may either inhibit or promote apoptosis, thus regulating the fate of the liver cancer cells. In this review, a concise overview of the pathogenesis of HCC is presented, with emphasis on new developments, including the role of endoplasmic reticulum stress, the implication of microRNAs and the role of gut microbiota. The characteristics of HCC associated with a specific liver disease are also described and a brief description of autophagy and apoptosis is provided. The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. The role of ferroptosis, a recently described specific pathway of regulated cell death, is presented. Finally, the potential therapeutic implications of autophagy and apoptosis in drug resistance are examined.

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“…Mitochondrial dysfunction mediates the accumulation of ROS and mtDNA damage, which may lead to the development of HCC. As found by Shetty et al, mitochondrial ROS levels doubled in the course of nitrosodiethylamine (NDEA)-induced HCC in mice, leading to DNA damage and proto-oncogene activation, which in turn promoted tumorigenesis [ 50 , 51 ]. In tumor cells, the inhibition of mitochondrial activity can transform these cells into tumor cells with mitochondrial dysfunction (P0), thus resulting in increased stem cell properties and stronger division ability.…”

Section: Mitochondrial Dysfunction and Chronic Liver Diseasementioning

confidence: 99%

“…[ [54][55][56] ROS During the development of HCC, ROS is increased. [50,51] mtDNA mtDNA is damaged by ROS, resulting in mitochondrial gene mutation. [49,50]…”

Section: Energy Metabolismmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Liver Disease

Zhao

Qin

et al. 2022

CIMB

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Mitochondria are generally considered the powerhouse of the cell, a small subcellular organelle that produces most of the cellular energy in the form of adenosine triphosphate (ATP). In addition, mitochondria are involved in various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested in different aspects, like increased mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, adenosine triphosphate (ATP) synthesis disorder, abnormal mitophagy, as well as changes in mitochondrial morphology and structure. Mitochondrial dysfunction is related to the occurrence and development of various chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic fatty liver (AFL), and non-alcoholic fatty liver (NAFL). In this review, we summarize and discuss the role and mechanisms of mitochondrial dysfunction in chronic liver disease, focusing on and discussing some of the latest studies on mitochondria and chronic liver disease.

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Mitochondria-targeted antioxidant, mito-TEMPO mitigates initiation phase of N-Nitrosodiethylamine-induced hepatocarcinogenesis

Cited by 14 publications

References 52 publications

Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity

Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

Mitochondrial Dysfunction and Chronic Liver Disease

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