Reza Norouzirad1, Hanieh Gholami2, Mahboubeh Ghanbari2, Mehdi Hedayati3, Pedro González-Muniesa4, Sajad Jeddi5, Asghar Ghasemi6. 1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Dezful University of Medical Sciences, Dezful, Iran. Electronic address: norouzirad@sbmu.ac.ir. 2. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: hedayati@endocrine.ac.ir. 4. University of Navarra, Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Pamplona, Spain; University of Navarra, Centre for Nutrition Research, School of Pharmacy and Nutrition, Pamplona, Spain; IdiSNA Navarra's Health Research Institute, Pamplona, Spain; CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain. Electronic address: pgonmun@unav.es. 5. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: sajad.jeddi@sbmu.ac.ir. 6. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
Abstract
AIMS: 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. MAIN METHODS: Fifty-six male Wistar rats (190-210 g) were divided into 8 groups: Controls (non-treated, nitrate-treated, O2-treated, and nitrate + O2-treated) and diabetes (non-treated, nitrate-treated, O2-treated, and nitrate + O2-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. KEY FINDINGS: Diabetic rats had increased oxidative stress and hyperoxia exacerbated it. In O2-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. SIGNIFICANCE: Our results showed that dietary nitrate attenuates hyperoxia-induced oxidative stress in type 2 diabetic rats.
AIMS: Hyperoxia has beneficial metabolic effects in type 2 diabetes. However, hyperoxia exacerbates already existing oxidative stress in type 2 diabetes. Nitrate, a nitric oxidedonor, 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 diabeticrats. MAIN METHODS: Fifty-six male Wistar rats (190-210 g) were divided into 8 groups: Controls (non-treated, nitrate-treated, O2-treated, and nitrate + O2-treated) and diabetes (non-treated, nitrate-treated, O2-treated, and nitrate + O2-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. KEY FINDINGS:Diabeticrats had increased oxidative stress and hyperoxia exacerbated it. In O2-diabeticrats, 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. SIGNIFICANCE: Our results showed that dietary nitrate attenuates hyperoxia-induced oxidative stress in type 2 diabeticrats.