MitoQ demonstrates connexin- and p53-mediated cancer chemoprevention in N-nitrosodiethylamine-induced hepatocarcinogenesis rodent model

Qsee, H.S.; Tambe, Prasad Kisan; De, Shounak; Bharati, Sanjay

doi:10.1016/j.taap.2022.116211

Cited by 7 publications

(5 citation statements)

References 54 publications

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“…Immunohistochemical analysis for 8-OHdG was carried out in intestinal tissue as described earlier (Qsee et al 2022 ). In brief, intestinal tissue Sects.…”

Section: Methodsmentioning

confidence: 99%

Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

2023

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Background Recent evidences highlight role of mitochondria in the development of 5-fluorouracil (5-FU)-induced intestinal toxicity. Mitochondria-targeted antioxidants are well-known for their protective effects in mitochondrial oxidative stress- mediated diseases. In the present study, we investigated protective effect of Mito-TEMPO in 5-FU-induced intestinal toxicity. Methods Mito-TEMPO (0.1 mg/kg b.w.) was administered intraperitoneally to male BALB/c mice for 7 days, followed by co-administration of 5-FU for next 4 days (intraperitoneal 12 mg/kg b.w.). Protective effect of Mito-TEMPO on intestinal toxicity was assessed in terms of histopathological alterations, modulation in inflammatory markers, apoptotic cell death, expression of 8-OhDG, mitochondrial functional status and oxidative stress. Results 5-FU administered animals showed altered intestinal histoarchitecture wherein a shortening and atrophy of the villi was observed. The crypts were disorganized and inflammatory cell infiltration was noted. Mito-TEMPO pre-protected animals demonstrated improved histoarchitecture with normalization of villus height, better organized crypts and reduced inflammatory cell infiltration. The inflammatory markers and myeloperoxidase activity were normalized in mito-TEMPO protected group. A significant reduction in intestinal apoptotic cell death and expression of 8-OhDG was also observed in mito-TEMPO group as compared to 5-FU group. Further, mtROS, mtLPO and mitochondrial antioxidant defense status were improved by mito-TEMPO. Conclusion Mito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.

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“…Immunohistochemical analysis for 8-OHdG was carried out in intestinal tissue as described earlier (Qsee et al 2022 ). In brief, intestinal tissue Sects.…”

Section: Methodsmentioning

confidence: 99%

Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

2023

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“…The immunohistochemistry for 8-OHdG was performed as described earlier [ 17 ]. Briefly, paraffin embedded cardiac tissue sections were deparaffinized and rehydrated in descending grades of alcohol.…”

Section: Methodsmentioning

confidence: 99%

“…Mitochondria from cardiomyocytes were isolated as described previously [ 18 ]. Mitochondrial oxidative stress was assessed in terms of mitochondrial lipid peroxidation (mtLPO) and mitochondrial reactive oxygen species (mtROS) as described earlier [ 17 ]. Briefly, levels of mtLPO were estimated by suspending mitochondrial fraction in Buege and Aust reagent, and centrifuged at 1000 × g (10 min).…”

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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“…300 It can suppress the initiation of hepatocarcinoma by regulating mtROS, connexins and the expression of p53 as a chemopreventive treatment. 301 DT-010, a synthetic product of danshensu and tetramethylpyrazine 303,304 Growing evidence has suggested that ROS derived from NOXs fam-ily may contribute to genomic instability, promoting the initiation of cancer and drug resistance. 305,306 A study conducted in vivo and in vitro found that NOX5-derived ROS could mediate epithelial cell proliferation and survival in prostate cancer.…”

Section: Targeting Mitochondrial Metabolismmentioning

confidence: 99%

“…MitoQ is an antioxidant targeting mitochondria that can localize to mitochondrial membrane and exert a long‐lasting function 300 . It can suppress the initiation of hepatocarcinoma by regulating mtROS, connexins and the expression of p53 as a chemopreventive treatment 301 . DT‐010, a synthetic product of danshensu and tetramethylpyrazine that can kill breast cancer cells via inhibiting ETC complex II, which can further be reversed by NAC, a cysteine compound that has an antioxidant effect 302 …”

Section: Ros and Cancer Immunotherapymentioning

confidence: 99%

Roles of reactive oxygen species in inflammation and cancer

Yu,

Liu,

Yang

et al. 2024

MedComm

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Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS‐mediated mechanisms for advancing cancer therapy and developing personalized treatments.

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MitoQ demonstrates connexin- and p53-mediated cancer chemoprevention in N-nitrosodiethylamine-induced hepatocarcinogenesis rodent model

Cited by 7 publications

References 54 publications

Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

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

Roles of reactive oxygen species in inflammation and cancer

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