Protective Effects of Mitoquinol Mesylate (MitoQ) Against DoxorubicinInduced Hepatotoxicity in Wistar Rats

Adisa RA(1), Odofin M(2), Oluwole-Banjo AK(3), Ayeni E(4), Linus V(5), Abdulkareem F(6),


(1) Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria.
(2) Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(3) Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria.
(4) Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(5) Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria.
(6) Department of Anatomic and Molecular Pathology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria.
Corresponding Author

Abstract


Background: Mitoquinol mesylate (MitoQ) is known for its hepatoprotection in several studies. Doxorubicin (DOX) is an extensively used chemotherapeutic drug with a high incidence of organ damage.

Objective: The present study was designed to investigate the possible protection of MitoQ against hepatic damage and oxidative stress induced by doxorubicin in Wistar rats.

Methods: Laboratory based randomized controlled pre-clinical trial conducted on 35 Wistar strain albino rats divided into 7 groups (n = 5) for experimental period of 21 days was done. Groups 13 were orally administered each of normal saline, 2.86 mg/ kg doxorubicin and co-administration of 2.86 mg/kg doxorubicin and silymarin (2.8 mg/kg), respectively. Groups 46 received oral co-administration of 2.86 mg/kg doxorubicin and varying concentrations of 10 mg/kg, 15 mg/kg, and 20 mg/kg MitoQ while the animals in Group 7 were orally administered only 20 mg/kg MitoQ. Hepatic toxicity was estimated by biochemical parameters and markers of oxidative stress.

Results: Doxorubicin induced significant elevation of AST, ALT, ALP, TG and cholesterol (p<0.05). Doxorubicin caused a reduction in HDL and albumin levels (p<0.05), as well as activity of SOD and level of GSH with a concomitant increase in liver MDA (p<0.05) and activity of glutathione peroxidase. MitoQ protected liver functions and other biochemical parameters (p<0.05). Increase in MDA level associated with a reduction in antioxidant enzymes in the doxorubicin group was alleviated by MitoQ treatment (p<0.05).

Conclusion: Our findings suggested MitoQ to be an effective intervention to counter hepatotoxicity induced by doxorubicin.


Keywords


Doxorubicin, Mitoquinol mesylate, Hepatotoxicity, Oxidative stress, Wistar rats

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