Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease

Bondor, Cosmina Ioana; Potra, Alina; Moldovan, Diana; Rusu, Crina; Pop, Mariana Ciorba; Muresan, Adriana; Vlăduţiu, Dan; Kacsó, Ina Maria

doi:10.1007/s11255-015-1004-2

Cited by 13 publications

(12 citation statements)

References 33 publications

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“…Some papers indicated that the significant increase in MDA levels and decrease in T-AOC levels in early stage of nephropathy in patients with T2D. 21,22 Our results also demonstrated that increase in MDA levels and decrease in T-AOC levels in the renal tissues from 4 weeks DM. The levels of T-AOC and MDA in renal tissues have good line correlations with renal histologic evaluation score, respectively.…”

Section: Discussionsupporting

confidence: 75%

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

et al. 2015

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Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes, which is associated with an increased oxidative stress induced by hyperglycemia and alterations in DJ-1/NF-E2-related factor-2 (Nrf2) pathway. In the present study, we investigated the role and the proper time nodes of DJ-1/Nrf2 pathway in the pathogenesis of DN. Diabetes mellitus (DM) model of rats was induced by intraperitoneal injection of streptozotocin (STZ) on male Sprague-Dawley (SD) rats. Then, the diabetic rats were divided into 4, 8 and 12 weeks groups. As early at 4 weeks of diabetes, renal histologic evaluation score, cystatin C (Cys C), b2-microglobulin (b2-MG) and malondialdehyde (MDA) levels were increased, and total antioxidative capacity (T-AOC) level was decreased as compared with that in the control group. The protein expressions of DJ-1, NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were upregulated compared with the control group from 4 weeks and further increased with the progression of DM. The protein expressions of DJ-1, Nrf2 and HO-1 in renal tissues have good line correlations with renal histologic evaluation score, respectively. Taken together, these results suggested that the activation of DJ-1/Nrf2 pathway was involved in the pathogenesis of diabetic nephropathy in rats.ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 75%

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

et al. 2015

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“…One study in adipocytes showed that oscillating high glucose exacerbated the suppression of adiponectin mRNA expression and secretion than constant high glucose [8]. Although the protective role of adiponectin against high glucose in various cell lines has been reported [9–11], its anti-apoptotic mechanism has not been completely understood. Adiponectin exerts anti-apoptotic effect under high glucose condition in HUVECs (human umbilical vein endothelial cells) by activating AMPK [9,12], but very less research has been done in tubular cells.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin attenuates high glucose-induced apoptosis through the AMPK/p38 MAPK signaling pathway in NRK-52E cells

et al. 2017

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Excessive apoptosis of proximal tubule cell is closely related to the development of diabetes. Recent evidence suggests that adiponectin (ADPN) protects cells from high glucose induced apoptosis. However, the precise mechanisms remain poorly understood. We sought to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) and AMP activated protein kinase (AMPK) in anti-apoptotic of adiponectin under high glucose condition in rat tubular NRK-52E cells. Cells were cultured in constant and oscillating high glucose media with or without recombinant rat adiponectin for 48 h. Cell counting kit-8 (CCK-8) was used to detect cell viability, flow cytometry and Hoechst Staining were applied to investigate cell apoptosis, and western blotting was used to examine protein expression, such as phospho-AMPK and phospho-p38MAPK. Exposure to oscillating high glucose exerted lower cell viability and higher early apoptosis than constant high glucose, which were both partially prevented by adiponectin. Further studies revealed that adiponectin suppressed p38MAPK phosphorylation, but led to an increase in AMPK α phosphorylation. Compared to stable high glucose group, blockage of p38MAPK cascade with SB203580 attenuated apoptosis significantly, but failed to affect the phosphorylation level of AMPK. While AMPK inhibitor, Compound C, increased apoptosis and remarkably inhibited the p38MAPK phosphorylation. Adiponectin exert a crucial protective role against apoptosis induced by high glucose via AMPK/p38MAPK pathway.

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“…Therefore our results do not confirm the assumption that oxidative stress and its resulting damage to DNA are increasing with T2DM progression. Most previous studies compared healthy individuals to T2DM patients and could detect induced oxidative stress in T2DM, represented through decreased FRAP-, GSH- and reduced thiols levels, whereas MDA, oxLDL, GSSG and F2-Isoprostanes were increased [20–24, 43, 44]. Additionally, strong linear association to HbA1c was reported for MDA, GSH and oxLDL [20, 45].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding antioxidant enzyme activities of SOD, CAT, GSH-Px, we could not detect any differences between the HbA1c groups. SOD and CAT activity was previously shown to be increased in T2DM compared to healthy controls [20, 43, 46, 47], while GSH-Px was decreased [20, 47]. However, evidence is not sound as some studies could not detect any differences between T2DM and healthy controls in these enzymes [46, 47].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2

et al. 2016

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BackgroundDiabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.MethodsFemale T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.ResultsNo significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.ConclusionBMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

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Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease

Abstract: Adiponectin is a significant predictor of MDA in early diabetic nephropathy, whereas SOD strongly depends only on glycemic control and is not directly related to adiponectin.

Cited by 13 publications

References 33 publications

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

Adiponectin attenuates high glucose-induced apoptosis through the AMPK/p38 MAPK signaling pathway in NRK-52E cells

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2

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