Effects of two- and twelve-weeks sodium-glucose cotransporter 2 inhibition on DNA and RNA oxidation: two randomized, placebo-controlled trials.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Free Radical Research Pub Date : 2023-02-01 DOI:10.1080/10715762.2023.2213820
Emil L Larsen, Andreas Andersen, Laura K Kjaer, Mie K Eickhoff, Marie Frimodt-Møller, Frederik Persson, Peter Rossing, Jens Lykkesfeldt, Filip K Knop, Tina Vilsbøll, Jørgen Rungby, Henrik E Poulsen
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Abstract

Animal studies have shown that SGLT2 inhibition decreases oxidative stress, which may explain the cardiovascular protective effects observed following SGLT2 inhibition treatment. Thus, we investigated the effects of two and twelve weeks SGLT2 inhibition on DNA and RNA oxidation. Individuals with type 2 diabetes (n = 31) were randomized to two weeks of treatment with the SGLT2 inhibitor empagliflozin treatment (25 mg once daily) or placebo. The primary outcome was changes in DNA and RNA oxidation measured as urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively. In another trial, individuals with type 2 diabetes (n = 35) were randomized to twelve weeks of dapagliflozin treatment (10 mg once daily) or placebo in a crossover study. Changes in urinary excretion of 8-oxodG and 8-oxoGuo were investigated as a posthoc analysis. Compared with placebo treatment, two weeks of empagliflozin treatment did not change urinary excretion of 8-oxodG (between-group difference: 0.3 nmol/24-hour (95% CI: -4.2 to 4.8)) or 8-oxoGuo (1.3 nmol/24-hour (95% CI: -4.7 to 7.3)). From a mean baseline 8-oxodG/creatinine urinary excretion of 1.34 nmol/mmol, dapagliflozin-treated individuals changed 8-oxodG/creatinine by -0.17 nmol/mmol (95% CI: -0.29 to -0.04) following twelve weeks of treatment, whereas placebo-treated individuals did not change 8-oxodG/creatinine (within-group effect: 0.10 nmol/mmol (95% CI: -0.02 to 0.22)) resulting in a significant between-group difference (p = 0.01). Urinary excretion of 8-oxoGuo was unaffected by dapagliflozin treatment. In conclusion, two weeks of empagliflozin treatment did not change DNA or RNA oxidation. However, a posthoc analysis revealed that longer-term dapagliflozin treatment decreased DNA oxidation. Clinicaltrials.gov: NCT02890745 and NCT02914691.HighlightsPlasma ferritin correlated with DNA and RNA oxidation in individuals with T2D.Twelve weeks dapagliflozin treatment decreased DNA oxidation.Dapagliflozin and empagliflozin treatment did not change RNA oxidation.Lipid peroxidation was unaffected by two weeks empagliflozin treatment.

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2周和12周钠-葡萄糖共转运蛋白2抑制对DNA和RNA氧化的影响:两项随机、安慰剂对照试验
动物研究表明,SGLT2抑制可降低氧化应激,这可能解释了SGLT2抑制治疗后观察到的心血管保护作用。因此,我们研究了2周和12周SGLT2抑制对DNA和RNA氧化的影响。2型糖尿病患者(n = 31)随机分为SGLT2抑制剂恩帕列净治疗(25 mg,每日一次)或安慰剂治疗两周。主要结局是通过尿液中8-氧-7,8-二氢-2'-脱氧鸟苷(8-oxodG)和8-氧-7,8-二氢鸟苷(8-oxoGuo)的排出来测量DNA和RNA氧化的变化。在另一项交叉研究中,2型糖尿病患者(n = 35)被随机分为12周的达格列净治疗组(10mg每日一次)或安慰剂组。尿中8-oxodG和8-oxoGuo的变化作为事后分析进行了研究。与安慰剂治疗相比,两周的恩格列净治疗没有改变尿中8-oxodG(组间差异:0.3 nmol/24小时(95% CI: -4.2至4.8))或8-oxoGuo (1.3 nmol/24小时(95% CI: -4.7至7.3))的排泄。从平均基线8-oxodG/肌酐尿排泄1.34 nmol/mmol开始,达格列净治疗个体在治疗12周后将8-oxodG/肌酐改变了-0.17 nmol/mmol (95% CI: -0.29至-0.04),而安慰剂治疗个体没有改变8-oxodG/肌酐(组内效应:0.10 nmol/mmol (95% CI: -0.02至0.22)),导致组间差异显著(p = 0.01)。8-oxoGuo尿排泄不受达格列净治疗的影响。总之,两周的恩格列净治疗没有改变DNA或RNA氧化。然而,事后分析显示,长期的达格列净治疗减少了DNA氧化。Clinicaltrials.gov: NCT02890745和NCT02914691。血浆铁蛋白与T2D患者DNA和RNA氧化相关。达格列净治疗12周后,DNA氧化降低。达格列净和恩格列净治疗没有改变RNA氧化。两周的恩格列净治疗未影响脂质过氧化。
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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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