Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney

Muthaian, Rupadevi; Pakirisamy, Rajaa Muthu; Parasuraman, Subramani; Raveendran, R

doi:10.4103/0976-500x.195898

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…Upregulation of Trpc1 may be a consequence of hemodynamic disturbances in the diabetic heart which in turn stimulates mechano-sensitive TRPC channels thereby providing an alternative entry pathway for Ca 2+ in the face of depressed L-type Ca 2+ current in AVN cells and reduced heart rate in STZ-induced diabetic heart ( 32 , 33 ). Previous studies have reported elevation of mean arterial pressure in STZ-induced diabetic rats which may in turn lead to hypertrophy of the heart which would be consistent with the increase in heart weight to body weight ratio, which in turn might elicit an effect on the mechano-sensitive channels ( 53 ).…”

Section: Discussionsupporting

confidence: 55%

Altered profile of mRNA expression in atrioventricular node of streptozotocin-induced diabetic rats

Howarth

Parekh

Jayaprakash

et al. 2017

Molecular Medicine Reports

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Prolonged action potential duration, reduced action potential firing rate, upstroke velocity and rate of diastolic depolarization have been demonstrated in atrioventricular node (AVN) cells from streptozotocin (STZ)-induced diabetic rats. To further clarify the molecular basis of these electrical disturbances, the mRNA profiles encoding a variety of proteins associated with the generation and conduction of electrical activity in the AVN, were evaluated in the STZ-induced diabetic rat heart. Expression of mRNA was measured in AVN biopsies using reverse transcription-quantitative polymerase chain reaction techniques. Notable differences in mRNA expression included upregulation of genes encoding membrane and intracellular Ca2+ transport, including solute carrier family 8 member A1, transient receptor potential channel 1, ryanodine receptor 2/3, hyperpolarization-activated cyclic-nucleotide 2 and 3, calcium channel voltage-dependent, β2 subunit and sodium channels 3a, 4a, 7a and 3b. In addition to this, potassium channels potassium voltage-gated channel subfamily A member 4, potassium channel calcium activated intermediate/small conductance subfamily N α member 2, potassium voltage-gated channel subfamily J members 3, 5, and 11, potassium channel subfamily K members 1, 2, 3 and natriuretic peptide B (BNP) were upregulated in AVN of STZ heart, compared with controls. Alterations in gene expression were associated with upregulation of various proteins including the inwardly rectifying, potassium channel Kir3.4, NCX1 and BNP. The present study demonstrated notable differences in the profile of mRNA encoding proteins associated with the generation, conduction and regulation of electrical signals in the AVN of the STZ-induced diabetic rat heart. These data will provide a basis for a substantial range of future studies to investigate whether variations in mRNA translate into alterations in electrophysiological function.

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Section: Discussionsupporting

confidence: 55%

Altered profile of mRNA expression in atrioventricular node of streptozotocin-induced diabetic rats

Howarth

Parekh

Jayaprakash

et al. 2017

Molecular Medicine Reports

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“…In the present study, the administration of STZ showed significant hyperglycemia, hypoinsulinemia, and significant oxidative stress with a marked increase in the levels of HbA1c, AGEs, cholesterol, TG, LDL, total lipids, urea, uric acid, creatinine, AST, ALT, ALP, bilirubin, CPK, and inflammatory markers including IL-6, TNF- α , and CRP, while C-peptide, HO-1, HDL, albumin, and amylase and growth factors like liver and serum IGF-1 levels markedly decreased. A variety of studies have demonstrated parallel results [ 26 – 29 ].…”

Section: Discussionmentioning

confidence: 92%

Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats

Elshemy

Asem

Allemailem

et al. 2021

Oxidative Medicine and Cellular Longevity

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Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. In the present study, we investigated the therapeutic potential of the liver and adipose MSC-CM in diabetic endothelial dysfunction compared with standard insulin therapy. Fifty adult male Sprague Dawley rats were divided equally into 5 groups as follows: control, diabetic, diabetic+insulin, diabetic+liver MSC-CM, and diabetic+adipose MSC-CM; all treatments continued for 4 weeks. Finally, we observed that liver MSC-CM therapy had the most apparent improvement in levels of blood glucose; HbA1c; AGEs; lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF-α, and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels compared with insulin and adipose MSCs-CM. Moreover, both the liver and adipose MSC-CM relieved the hyperglycemic status by improving pancreatic islet β cell regeneration, promoting the conversion of alpha cells to beta cells, reducing insulin resistance, and protecting pancreatic tissues against oxidative stress-induced injury as well as possessing the ability to modulate immunity and angiogenesis. These results indicated that MSC-CM infusion has therapeutic effects in T2DM rats and may be a promising novel therapeutic target.

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“…Oxidative stress is essential in the development of injury following CIRI [6] and these effects are known to be exacerbated in patients with diabetes [7]. Additionally, the inflammation induced by CIRI is significantly enhanced in patients with diabetes [8]. An in vitro study also found that high glucose induces ROS production and activates cytokine secretion [9].…”

Section: Introductionmentioning

confidence: 86%

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng¹,

Ren²,

Zhu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX₂ (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91^phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91^phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91^phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91^phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91^phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91^phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91^phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91^phoxsiRNA. Conclusion: Knockdown of gp91^phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model.

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Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney

Cited by 6 publications

References 35 publications

Altered profile of mRNA expression in atrioventricular node of streptozotocin-induced diabetic rats

Altered profile of mRNA expression in atrioventricular node of streptozotocin-induced diabetic rats

Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

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