Document Type : Original Article(s)

Authors

• Fatemeh Samimi ^{1, 2}
• Maryam Baazm ^{3, 4}
• Zahra Nadi ³
• Sanaz Dastghaib ⁵
• Mehri Rezaei ¹
• Farideh Jalali-Mashayekhi ^{1, 4}

¹ Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran

² Department of Biochemistry and Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

³ Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran

⁴ Research Center and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran

⁵ Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10’s antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway.
Methods: This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD’s or Tukey’s post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant.
Results: The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNAs expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group. 
Conclusion: The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway.

Keywords

• Coenzyme Q10
• Diabetes mellitus
• Nrf2/Keap1/ARE pathway
• Oxidative stress
• Rats