Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Dezful University of Medical Sciences, Dezful, Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Life Sci. 2019 Aug 1;230:188-196. doi: 10.1016/j.lfs.2019.05.068. Epub 2019 May 28.
Hyperoxia has beneficial metabolic effects in type 2 diabetes. However, hyperoxia exacerbates already existing oxidative stress in type 2 diabetes. Nitrate, a nitric oxide donor, is an effective new treatment in type 2 diabetes and also has antioxidant properties. The aim of this study was to determine whether nitrate administration can attenuate hyperoxia-induced oxidative stress in obese type 2 diabetic rats.
Fifty-six male Wistar rats (190-210 g) were divided into 8 groups: Controls (non-treated, nitrate-treated, O-treated, and nitrate + O-treated) and diabetes (non-treated, nitrate-treated, O-treated, and nitrate + O-treated). Diabetes was induced using high-fat diet and low-dose of streptozotocin (30 mg/kg). Rats in intervention groups, were exposed to 95% oxygen and consumed sodium nitrate (100 mg/L) in drinking water. Serum fasting glucose, oxidized (GSSG) and reduced (GSH) glutathiones, total oxidant status (TOS), catalase and superoxide dismutase (SOD) activities, and total antioxidant capacity (TAC) were measured after intervention. Oxidative stress index (OSI) was calculated as TOS/TAC ratio.
Diabetic rats had increased oxidative stress and hyperoxia exacerbated it. In O-diabetic rats, nitrate decreased GSSG (102.7 ± 2.1 vs. 236.0 ± 20.1 μM, P < 0.001), TOS (67.7 ± 7.3 vs. 104 ± 3.8 μM, P < 0.001), and OSI (0.44 ± 0.04 vs. 0.91 ± 0.07, P < 0.001) and increased catalase (2.8 ± 0.13 vs. 1.8 ± 0.21 KU/L, P = 0.014), SOD (53.4 ± 1.5 vs. 38.4 ± 1.2 U/mL, P < 0.001), GSH (43.7 ± 1.4 vs. 17.8 ± 0.5 mM, P = 0.003), TAC (152.5 ± 1.9 vs. 116.7 ± 5.0 mM, P < 0.001), and GSH/GSSG ratio (0.43 ± 0.01 vs. 0.08 ± 0.01, P = 0.005). Nitrate also potentiated effects of hyperoxia on decreasing fasting glucose.
Our results showed that dietary nitrate attenuates hyperoxia-induced oxidative stress in type 2 diabetic rats.
富氧环境对 2 型糖尿病患者具有有益的代谢作用。然而，富氧环境会加重 2 型糖尿病患者已有的氧化应激。硝酸盐是一种有效的新型 2 型糖尿病治疗药物，具有抗氧化特性。本研究旨在确定硝酸盐的给药是否可以减轻肥胖 2 型糖尿病大鼠的高氧诱导的氧化应激。
将 56 只雄性 Wistar 大鼠（190-210g）分为 8 组：对照组（未治疗、硝酸盐治疗、高氧治疗和硝酸盐+高氧治疗）和糖尿病组（未治疗、硝酸盐治疗、高氧治疗和硝酸盐+高氧治疗）。糖尿病通过高脂肪饮食和小剂量链脲佐菌素（30mg/kg）诱导。干预组大鼠暴露于 95%氧气中，并饮用含有硝酸钠（100mg/L）的水。干预后测量血清空腹血糖、氧化型（GSSG）和还原型（GSH）谷胱甘肽、总氧化剂状态（TOS）、过氧化氢酶和超氧化物歧化酶（SOD）活性以及总抗氧化能力（TAC）。氧化应激指数（OSI）计算为 TOS/TAC 比值。
糖尿病大鼠的氧化应激增加，而高氧环境使其恶化。在高氧糖尿病大鼠中，硝酸盐降低了 GSSG（102.7±2.1 与 236.0±20.1μM，P<0.001）、TOS（67.7±7.3 与 104±3.8μM，P<0.001）和 OSI（0.44±0.04 与 0.91±0.07，P<0.001），并增加了过氧化氢酶（2.8±0.13 与 1.8±0.21KU/L，P=0.014）、SOD（53.4±1.5 与 38.4±1.2U/mL，P<0.001）、GSH（43.7±1.4 与 17.8±0.5mM，P=0.003）、TAC（152.5±1.9 与 116.7±5.0mM，P<0.001）和 GSH/GSSG 比值（0.43±0.01 与 0.08±0.01，P=0.005）。硝酸盐还增强了高氧对降低空腹血糖的作用。
我们的结果表明，饮食中的硝酸盐可减轻 2 型糖尿病大鼠的高氧诱导的氧化应激。
