Rad Nikoo Roustaei, Movahedian Ahmad, Feizi Awat, Aminorroaya Ashraf, Aarabi Mohammad Hosein
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2022 Jan 15;17(2):219-230. doi: 10.4103/1735-5362.335179. eCollection 2022 Apr.
Since the critical role of oxidative stress in the pathogenesis and complications of type 2 diabetes mellitus (T2DM) has been proven, antioxidant therapy is considered an applicable strategy to control T2DM development. This study aimed at evaluating the effect of astaxanthin (AST) supplementation combined with metformin on oxidative indices and antioxidant defenses in T2DM patients.
In this randomized, double-blind placebo-controlled trial, 50 T2DM subjects receiving metformin were supplemented with 10 mg/day AST or placebo for 12 weeks. Malondialdehyde concentration and serum total antioxidant capacity (TAC) were assessed as oxidative indices. We also evaluated NF-E2-related factor2 (Nrf2) as the most critical transcription factor of antioxidant defense. Moreover, the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase were calculated.
FINDINGS/RESULTS: AST supplementation-metformin combination caused a significant increase in SOD and catalase activities, as well as inducing Nrf2 protein expression compared to the placebo group. Significant changes in serum malondialdehyde and TAC between the AST group and placebo group after supplementation were not observed, although a significant increase was observed in TAC within the AST group after supplementation (32.67 ± 6.73) to before (25.86 ± 5.98). These results remained without change after adjustment for potential confounders.
Our study demonstrated that AST supplementation controlled oxidative stress through a synergistic effect with metformin and ameliorated overall antioxidant capacity by inducing Nrf2 transcription factor and activating SOD and catalase in T2DM patients. As a result, AST and metformin combination therapy can be considered beneficial in modifying oxidative stress and preventing T2DM complications.
鉴于氧化应激在2型糖尿病（T2DM）发病机制及并发症中的关键作用已得到证实，抗氧化治疗被视为控制T2DM进展的一种可行策略。本研究旨在评估补充虾青素（AST）联合二甲双胍对T2DM患者氧化指标及抗氧化防御的影响。
在这项随机、双盲、安慰剂对照试验中，50名接受二甲双胍治疗的T2DM受试者被补充10毫克/天的AST或安慰剂，为期12周。评估丙二醛浓度和血清总抗氧化能力（TAC）作为氧化指标。我们还评估了作为抗氧化防御最关键转录因子的核因子E2相关因子2（Nrf2）。此外，计算了抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶的活性。
与安慰剂组相比，补充AST联合二甲双胍可显著提高SOD和过氧化氢酶的活性，并诱导Nrf2蛋白表达。补充后，AST组与安慰剂组之间血清丙二醛和TAC未观察到显著变化，尽管补充后AST组内TAC较之前（25.86±5.98）有显著增加（32.67±6.73）。在对潜在混杂因素进行调整后，这些结果保持不变。
我们的研究表明，补充AST通过与二甲双胍的协同作用控制氧化应激，并通过诱导Nrf2转录因子和激活T2DM患者的SOD和过氧化氢酶来改善整体抗氧化能力。因此，AST与二甲双胍联合治疗在改善氧化应激和预防T2DM并发症方面可能是有益的。
