Toxicological Research

  • 제38권3호
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  • Pages.275-291
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  • 2022
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

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

  • Adisa, Rahmat Adetutu (Laboratories for Bio-membranes and Cancer Research, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of University of Lagos) ;
  • Sulaimon, Lateef Adegboyega (Laboratories for Bio-membranes and Cancer Research, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of University of Lagos) ;
  • Okeke, Ebele Geraldine (Laboratories for Bio-membranes and Cancer Research, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of University of Lagos) ;
  • Ariyo, Olubukola Christianah (Laboratories for Bio-membranes and Cancer Research, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of University of Lagos) ;
  • Abdulkareem, Fatimah B. (Department of Anatomic and Molecular Pathology, Faculty of Basic Medical Sciences,, College of Medicine of University of Lagos)
  • 투고 : 2021.02.15
  • 심사 : 2021.09.07
  • 발행 : 2022.07.15
⟨ 이전 논문 다음 논문 ⟩

초록

Diethyl nitrosamine (DEN) induced cirrhosis-hepatocellular carcinoma (HCC) model associates cancer progression with oxidative stress and mitochondrial dysfunction. This study investigated the effects of mitoquinol mesylate (MitoQ), a mitochondrial-targeted antioxidant on DEN-induced oxidative damage in HCC Wistar rats. Fifty male Wistar rats were randomly divided into fve groups. Healthy control, DEN, and MitoQ groups were orally administered exactly 10 mg/kg of distilled water, DEN, and MitoQ, respectively for 16 weeks. Animals in the MitoQ+DEN group were pre-treated with MitoQ for a week followed by co-administration of 10 mg/kg each of MitoQ and DEN. DEN+MitoQ group received DEN for 8 weeks, then co-administration of 10 mg/kg each of DEN and MitoQ till the end of 16th week. Survival index, tumour incidence, hematological profile, liver function indices, lipid profile, mitochondrial membrane composition, mitochondrial respiratory enzymes, and antioxidant defense status in both mitochondrial and post-mitochondrial fractions plus expression of antioxidant genes were assessed. In MitoQ+DEN and DEN+MitoQ groups, 80% survival occurred while tumour incidence decreased by 60% and 40% respectively, compared to the DEN-only treated group. Similarly, MitoQ-administered groups showed a significant (p < 0.05) decrease in the activities of liver function enzymes while hemoglobin concentration, red blood cell count, and packed cell volume were significantly elevated compared to the DEN-only treated group. Administration of MitoQ to the DEN-intoxicated groups successfully enhanced the activities of mitochondrial F1F0-ATPase and succinate dehydrogenase; and up-regulated the expression and activities of SOD2, CAT, and GPx1. Macroscopic and microscopic features indicated a reversal of DEN-induced hepatocellular degeneration in the MitoQ +DEN and DEN+MitoQ groups. These data revealed that MitoQ intervention attenuated DEN-induced oxidative stress through modulation of mitochondrial antioxidant defense systems and alleviated the burden of HCC as a chemotherapeutic agent.

키워드

과제정보

The authors appreciate the technical assistance of Mr. Chijioke Chimeremeze of the Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.

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