Open AccessMitoubiquinol Mesylate Attenuated Diethyl Nitrosamine–Induced Hepatocellular Carcinoma Through Modulation of Mitochondrial Antioxidant Defense Systems
Author(s) -
Adisa Rahmat Adetutu,
Sulaimon Lateef Adegboyega,
Ebele Geraldine Okeke,
Ariyo Oc,
Abdulkareem Fatimah Biade
Publication year - 2020
Publication title -
jco global oncology
Language(s) - English
Resource type - Journals
ISSN - 2687-8941
DOI - 10.1200/go.20.20000
Subject(s) - hepatocellular carcinoma , oxidative stress , pharmacology , antioxidant , medicine , cirrhosis , chemistry , cancer , apoptosis , biochemistry
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) between activities of mitochondrial F 1 F 0 -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.