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

Author(s):  
Rahmat Adetutu Adisa ◽  
Lateef Adegboyega Sulaimon ◽  
Ebele Geraldine Okeke ◽  
Olubukola Christianah Ariyo ◽  
Fatimah B. Abdulkareem
2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 9-9
Author(s):  
Adisa Rahmat Adetutu ◽  
Sulaimon Lateef Adegboyega ◽  
Okeke Ebele Geraldine ◽  
Ariyo OC ◽  
Abdulkareem Fatimah Biade

PURPOSE Hepatocellular carcinoma (HCC) is a highly malignant cancer, with a high recurrence rate and a poor prognosis. Diethyl nitrosamine (DEN) cirrhosis HCC–induced model has revealed an association of cancer progression with oxidative stress and mitochondrial dysfunction. This study investigated the effects of mitoubiquinol mesylate (MitoQ), a mitochondrial targeted antioxidant derivative from ubiquinone on DEN-induced oxidative damage in HCC Wistar rats. METHODS Fifty male Wistar rats were randomly divided into 5 groups, 10 rats per group. Groups A, B, and C received distilled water 10 mL/kg DEN, and MitoQ orally for 16 weeks, respectively. Animals in group D were pretreated with MitoQ for 1 week followed by coadministration of MitoQ and DEN (protective effect), whereas group E received DEN for 8 weeks, then coadministration of DEN and MitoQ (therapeutic effect) until the end of the study. Survival index, tumor incidence, liver function indices, hematologic profile, mitochondrial respiratory enzymes, and antioxidant defense status were assessed. RESULTS Data obtained show that rats in groups D and E had 80% survival and decreased tumor incidence (40% and 60%, respectively) compared with group B. Similarly, MitoQ significantly ( P < .05) decreased the activities of liver function enzymes, while hemoglobin concentration, red blood cell count, and lymphocytes levels were significantly elevated compared with the DEN-only group. Furthermore, MitoQ significantly ( P < .05) protected the liver from DEN-induced oxidative damage; however, there was no significant difference ( P > .05) between activities of mitochondrial F1F0-ATPase and succinate dehydrogenase of groups A, B, D, and E, respectively, although these enzyme activities were significantly ( P < .05) elevated in group C. Macroscopic and microscopic features indicated a reversal of DEN-induced cellular degeneration in hepatocytes. CONCLUSION These data suggest that MitoQ treatment for 16 weeks attenuated DEN-induced oxidative stress indices via modulation of mitochondrial antioxidant defense systems and could alleviate the burden of HCC as a chemotherapeutic agent.


2021 ◽  
pp. 94-143
Author(s):  
Carmen Cecilia Espíndola Díaz

2020 ◽  
Vol 2020 ◽  
pp. 1-29 ◽  
Author(s):  
Rossella D’Oria ◽  
Rossella Schipani ◽  
Anna Leonardini ◽  
Annalisa Natalicchio ◽  
Sebastio Perrini ◽  
...  

Reactive oxygen species (ROS) are highly reactive chemical species containing oxygen, controlled by both enzymatic and nonenzymatic antioxidant defense systems. In the heart, ROS play an important role in cell homeostasis, by modulating cell proliferation, differentiation, and excitation-contraction coupling. Oxidative stress occurs when ROS production exceeds the buffering capacity of the antioxidant defense systems, leading to cellular and molecular abnormalities, ultimately resulting in cardiac dysfunction. In this review, we will discuss the physiological sources of ROS in the heart, the mechanisms of oxidative stress-related myocardial injury, and the implications of experimental studies and clinical trials with antioxidant therapies in cardiovascular diseases.


2019 ◽  
Vol 20 (15) ◽  
pp. 3729 ◽  
Author(s):  
Shuwu Zhang ◽  
Bingliang Xu ◽  
Yantai Gan

Salt stress is one of the major abiotic stresses limiting crop growth and productivity worldwide. Species of Trichoderma are widely recognized for their bio-control abilities, but little information is regarding to the ability and mechanisms of their promoting plant growth and enhancing plant tolerance to different levels of salt stress. Hence, we determined (i) the role of Trichoderma longibrachiatum T6 (TL-6) in promoting wheat (Triticum aestivum L.) seed germination and seedling growth under different levels of salt stress, and (ii) the mechanisms responsible for the enhanced tolerance of wheat to salt stress by TL-6. Wheat seeds treated with or without TL-6 were grown under different levels of salt stress in controlled environmental conditions. As such, the TL-6 treatments promoted seed germination and increased the shoot and root weights of wheat seedlings under both non-stress and salt-stress conditions. Wheat seedlings with TL-6 treatments under different levels of NaCl stress increased proline content by an average of 11%, ascorbate 15%, and glutathione 28%; and decreased the contents of malondialdehyde (MDA) by an average of 19% and hydrogen peroxide (H2O2) 13%. The TL-6 treatments induced the transcriptional level of reactive oxygen species (ROS) scavenging enzymes, leading to the increases of glutathione s-transferase (GST) by an average of 17%, glutathione peroxidase (GPX) 16%, ascorbate peroxidase (APX) 17%, glutathione reductase (GR) 18%, dehydroascorbate reductase (DHAR) 5%. Our results indicate that the beneficial strain of TL-6 effectively scavenged ROS under NaCl stress through modulating the activity of ROS scavenging enzymes, regulating the transcriptional levels of ROS scavenging enzyme gene expression, and enhancing the nonenzymatic antioxidants in wheat seedling in response to salt stress. Our present study provides a new insight into the mechanisms of TL-6 can activate the enzymatic and nonenzymatic antioxidant defense systems and enhance wheat seedling tolerance to different levels of salt stress at physiological, biochemical and molecular levels.


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