Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

Yaribeygi, Habib; Sathyapalan, Thozhukat; Atkin, Stephen L.; Sahebkar, Amirhossein

doi:10.1155/2020/8609213

Cited by 445 publications

(359 citation statements)

References 149 publications

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“…6 Then, the oxidative stress and other redox cascades initiated by interleukin (IL)-6, IL-8, and nuclear factor kappa-light-chain-enhancer of activated B cells take place, leading to progressive cell damage independent from the causative organisms. 6,25,26 Both Cu and Zn are considered as antioxidant micronutrients, which minimize the inflammatory conditions resulting from oxidative stress. Both elements also play significant roles in the immune system functions including the viability, differentiation, and function of the cells of innate and adaptive response and the production of antibodies.…”

Section: Discussionmentioning

confidence: 99%

Association between DNA Damage and Serum Levels of Copper, Zinc, and Selenium in Full-Term Neonates with Late-Onset Sepsis

Wahby

Elwassif

Magdy

et al. 2020

Journal of Pediatric Infectious Diseases

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Objective The alteration in certain trace elements is usually associated with impaired immune function and higher oxidative stress. Therefore, these elements are suggested to play an important role in the pathogenesis of neonatal sepsis. We aimed to evaluate copper (Cu), zinc (Zn), and selenium (Se) serum levels in full-term neonates with late-onset sepsis (LOS) and correlate these levels with DNA damage and other risk factors of sepsis. Methods The study included a group of 100 neonates diagnosed with sepsis serving as the case group and another one of 60 neonates serving as the control group. DNA damage was assessed using the comet assay method and trace elements were measured using inductively coupled plasma mass spectrometry. Results Compared with controls, the percentage of DNA damage was significantly elevated in patients with sepsis, while serum levels of Cu, Zn, and Se were markedly decreased (p = 0.001). A strong negative correlation was revealed between Se and DNA damage (r = −0.6, p = 0.001). However, no correlations were found between Cu or Zn and DNA damage. Univariate logistic regression analysis revealed that DNA damage as well as Cu, Zn, and Se serum levels can be considered as relevant risk factors for neonatal sepsis (p = 0.008, 0.004, 0.004, and 0.003, respectively). Receiver-operating characteristic curve analysis showed that the strongest indicator for neonatal sepsis was Se (area under the curve [AUC] = 0.94, confidence interval [CI] = 0.9–0.98, p = 0.001), followed by Cu (AUC = 0.9, CI = 0.85–0.96, p = 0.001), and then Zn (AUC = 0.87, CI = 0.8–0.93, p = 0.001). Conclusion The percentage of DNA damage may help in the assessment of neonatal sepsis severity. Altered levels of Cu, Zn, and Se may play significant role in the pathogenesis of neonatal sepsis. Se serum level is strongly correlated with percentage of DNA damage. Therefore, Se can predict the severity of LOS.

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Section: Discussionmentioning

confidence: 99%

Association between DNA Damage and Serum Levels of Copper, Zinc, and Selenium in Full-Term Neonates with Late-Onset Sepsis

Wahby

Elwassif

Magdy

et al. 2020

Journal of Pediatric Infectious Diseases

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“…Several studies have shown that diabetes can lead to DR by several mechanisms including the polyol pathway [5], non-enzymatic glycation [6], activation of protein kinase C [7], oxidative stress [8][9][10][11][12], and inflammation [13]. Oxidative stress is considered to be one of the crucial causative factors in the development of DR, in combination with other biochemical imbalances, leading to both structural and functional changes and also promoting an increased loss of capillary cells in the microvasculature of the retina [11,12]. In addition, a significant body of evidence supports the role of proinflammatory cytokines, chemokines, and other inflammatory mediators in the pathogenesis of DR, leading to chronic low-grade inflammation of the retina and eventually to neovascularization [14].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Protects against Oxidative Stress and Inflammation in Human Retinal Cells

et al. 2020

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Diabetic retinopathy is a vision-threatening microvascular complication of diabetes and is one of the leading causes of blindness. Oxidative stress and inflammation play a major role in its pathogenesis, and new therapies counteracting these contributors could be of great interest. In the current study, we investigated the role of vitamin D against oxidative stress and inflammation in human retinal pigment epithelium (RPE) and human retinal endothelial cell lines. We demonstrate that vitamin D effectively counteracts the oxidative stress induced by hydrogen peroxide (H2O2). In addition, the increased levels of proinflammatory proteins such as Interleukin (IL)-6, IL-8, Monocyte chemoattractant protein (MCP)-1, Interferon (IFN)-γ, and tumor necrosis factor (TNF)-α triggered by lipopolysaccharide (LPS) exposure were significantly decreased by vitamin D addition. Interestingly, the increased IL-18 only decreased by vitamin D addition in endothelial cells but not in RPE cells, suggesting a main antiangiogenic role under inflammatory conditions. Moreover, H2O2 and LPS induced the alteration and morphological damage of tight junctions in adult retinal pigment epithelium (ARPE-19) cells that were restored under oxidative and inflammatory conditions by the addition of vitamin D to the media. In conclusion, our data suggest that vitamin D could protect the retina by enhancing antioxidant defense and through exhibiting anti-inflammatory properties.

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“…Oxidative stress is involved in the pathogenesis of DN, which is the basis of EMT. MDA level reflects the ability of the body to resist oxidative stress, 37 and oxidative damage can be prevented by enhancing the activities of antioxidant enzymes, including CAT, GSH-Px, and SOD, which strengthen the response of the antioxidant defense system. 38 In this study, Formononetin significantly decreased the level of MDA, and increased SOD,GSH-Px, and CAT levels.…”

Section: Discussionmentioning

confidence: 99%

<p>Renoprotective Effect of Formononetin by Suppressing Smad3 Expression in Db/Db Mice</p>

Zhuang

Jiang

Huang

et al. 2020

DMSO

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Purpose: Glomerular sclerosis and renal interstitial fibrosis are the most important pathologies in the development of kidney damage under diabetic conditions. Smad3 plays antagonistic roles in high glucose-induced renal tubular fibrosis, which is an important treatment target for diabetic nephropathy (DN). Formononetin (FMN) has multiple effects on diabetic vascular complications including DN. However, whether it plays an anti-fibrosis role by regulating smad3 is unclear. The purpose of this study was to evaluate the renoprotective effect of FMN by suppressing smad3 expression in db/db mice. Methods: FMN was orally administered to db/db mice with a dose of 25 or 50 mg/kg/day for 8 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examinations. The expressions of proteins and mRNA associated with renal fibrosis were determined by biochemical, histological, immunofluorescence, and real-time PCR analysis. Results: The results showed that FMN substantially improved the glucolipid metabolism, reduced the oxidative stress, and protected renal function in db/db mice. Meanwhile, protein and mRNA expression of smad3 and related regulatory factor of extracellular matrix deposition were significantly suppressed. Conclusion: The present study suggested that FMN has a good renoprotective effect in DN, which plays an anti-fibrosis role in db/db mice by suppressing the expression of smad3.

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Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

Cited by 445 publications

References 149 publications

Association between DNA Damage and Serum Levels of Copper, Zinc, and Selenium in Full-Term Neonates with Late-Onset Sepsis

Association between DNA Damage and Serum Levels of Copper, Zinc, and Selenium in Full-Term Neonates with Late-Onset Sepsis

Vitamin D Protects against Oxidative Stress and Inflammation in Human Retinal Cells

<p>Renoprotective Effect of Formononetin by Suppressing Smad3 Expression in Db/Db Mice</p>

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