Sahar Khaleel - Academia.edu (original) (raw)

Papers by Sahar Khaleel

Research paper thumbnail of Cytoglobin has potent superoxide dismutase function

Proceedings of the National Academy of Sciences, 2021

Significance We identified a novel function of cytoglobin (Cygb) as an efficient superoxide dismu... more Significance We identified a novel function of cytoglobin (Cygb) as an efficient superoxide dismutase (SOD) with a high–bimolecular dismutation rate on the order of 10 8 M −1 ⋅ s −1 . It is the first Fe-centered SOD identified in mammalian cells and the only member of the globin family shown to have potent SOD activity. This SOD function of Cygb may serve to explain the prior reports of its antioxidative activity and the toxicities and disease seen with its genetic deletion, including the increased incidence of tumors. Combined with its potent NO dioxygenase activity, Cygb would be highly effective in decreasing both O 2 •− and NO levels, serving to decrease the formation of peroxynitrite and secondary oxidative injury.

Research paper thumbnail of Electronic Cigarette Exposure Induces Vascular Endothelial Dysfunction with NADPH Oxidase Activation and eNOS Uncoupling

Research paper thumbnail of Figure-5_PNAS

Figure 5 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 5 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-4_PNAS

Figure 4 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 4 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 file for Figure 4 is included.<br>

Research paper thumbnail of Figure-2_PNAS

Figure 2 of PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The Sigma... more Figure 2 of PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel of the figure are included.<br>

Research paper thumbnail of Figure-1_PNAS

Figure 1 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function.<br... more Figure 1 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function.<br>

Research paper thumbnail of Figure-7_PNAS

Figure 7 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 7 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-6_PNAS

Figure 6 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 6 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-9_PNAS

Figure 9 of the PNAS article: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot ... more Figure 9 of the PNAS article: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot files for each of the panels are included. The image file of the gel in Panel A is also included.<br>

Research paper thumbnail of Figure-8_PNAS

Figure 8 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 8 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-3_PNAS

Figure 3 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 3 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 file for each panel of the figure is included.<br>

Research paper thumbnail of Figure-10_PNAS

Figure 10 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The ... more Figure 10 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The PowerPoint file of the figure build and the GraphPad Prism file of the bar graph are included.<br>

Research paper thumbnail of Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling

American Journal of Physiology-Heart and Circulatory Physiology, 2022

Underlying mechanisms of e-cig-induced vascular endothelial dysfunction are delineated. e-cig exp... more Underlying mechanisms of e-cig-induced vascular endothelial dysfunction are delineated. e-cig exposure activates and increases expression of NADPH oxidase and disrupts activation and coupling of eNOS, leading to a vicious cycle of superoxide generation and peroxynitrite formation, with tetrahydrobiopterin depletion, causing loss of NO that triggers vascular endothelial dysfunction. This process is progressive, increasing with the duration of e-cig exposure, and is more severe in the presence of nicotine, but observed even with nicotine-free vaping.

Research paper thumbnail of Mechanism of NO Decay in Vascular Smooth Muscle Cells: Role of Cytoglobin and Identification of its Cellular Reducing System

Research paper thumbnail of Role of cytoglobin in cigarette smoke constituent-induced loss of nitric oxide bioavailability in vascular smooth muscle cells

Nitric Oxide, 2021

Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vasc... more Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vascular smooth muscle cells (VSMCs) and is crucial for the regulation of vascular tone. In the presence of its requisite cytochrome B5a (B5)/ B5 reductase-isoform-3 (B5R) reducing system, Cygb controls NO metabolism through the oxygen-dependent process of NO dioxygenation. Tobacco cigarette smoking (TCS) induces vascular dysfunction; however, the role of Cygb in the pathophysiology of TCS-induced cardiovascular disease has not been previously investigated. While TCS impairs NO biosynthesis, its effect on NO metabolism remains unclear. Therefore, we performed studies in aortic VSMCs with tobacco smoke extract (TSE) exposure to investigate the effects of cigarette smoke constituents on the rates of NO decay, with focus on the alterations that occur in the process of Cygb-mediated NO metabolism. TSE greatly enhanced the rates of NO metabolism by VSMCs. An initial increase in superoxide-mediated NO degradation was seen at 4 hours of exposure. This was followed by much larger progressive increases at 24 and 48 hours, accompanied by parallel increases in the expression of Cygb and B5/B5R. siRNA-mediated Cygb knockdown greatly decreased these TSE-induced elevations in NO decay rates. Therefore, upregulation of the levels of Cygb and its reducing system accounted for the large increase in NO metabolism rate seen after 24 hours of TSE exposure. Thus, increased Cygb-mediated NO degradation would contribute to TCS-induced vascular dysfunction and partial inhibition of Cygb expression or its NO dioxygenase function could be a promising therapeutic target to prevent secondary cardiovascular disease.

Research paper thumbnail of Defining the reducing system of the NO dioxygenase cytoglobin in vascular smooth muscle cells and its critical role in regulating cellular NO decay

Journal of Biological Chemistry, 2021

In smooth muscle, cytoglobin (Cygb) functions as a potent nitric oxide (NO) dioxygenase and regul... more In smooth muscle, cytoglobin (Cygb) functions as a potent nitric oxide (NO) dioxygenase and regulates NO metabolism and vascular tone. Major questions remain regarding which cellular reducing systems regulate Cygb-mediated NO metabolism. To better define the Cygb-mediated NO dioxygenation process in vascular smooth muscle cells (SMCs), and the requisite reducing systems that regulate cellular NO decay, we assessed the intracellular concentrations of Cygb and its putative reducing systems and examined their roles in the process of NO decay. Cygb and the reducing systems, cytochrome b5 (B5)/cytochrome b5 reductase (B5R) and cytochrome P450 reductase (CPR) were measured in aortic SMCs. Intracellular Cygb concentration was estimated as 3.5 μM, while B5R, B5, and CPR were 0.88, 0.38, and 0.15 μM, respectively. NO decay in SMCs was measured following bolus addition of NO to air-equilibrated cells. siRNA-mediated knockdown experiments indicated that ∼78% of NO metabolism in SMCs is Cygb-dependent. Of this, ∼87% was B5R- and B5-dependent. CPR knockdown resulted in a small decrease in the NO dioxygenation rate (VNO), while depletion of ascorbate had no effect. Kinetic analysis of VNO for the B5/B5R/Cygb system with variation of B5 or B5R concentrations from their SMC levels showed that VNO exhibits apparent Michaelis–Menten behavior for B5 and B5R. In contrast, linear variation was seen with change in Cygb concentration. Overall, B5/B5R was demonstrated to be the major reducing system supporting Cygb-mediated NO metabolism in SMCs with changes in cellular B5/B5R levels modulating the process of NO decay.

Research paper thumbnail of C‐phycocyanin protects against ethanol‐induced gastric ulcers in rats: Role of HMGB1/NLRP3/NF‐κB pathway

Basic & Clinical Pharmacology & Toxicology, 2020

Gastric ulcer is a widespread inflammatory disease with high socio‐economic burden. C‐phycocyanin... more Gastric ulcer is a widespread inflammatory disease with high socio‐economic burden. C‐phycocyanin is one of the active constituents of Spirulina microalgae, and although it is well known for its antioxidant and anti‐inflammatory properties, its protective effects against gastric ulcer have not yet been identified. High‐mobility group box 1 (HMGB1) is a nuclear protein that, once secreted extracellularly, initiates several inflammatory reactions, and it is involved in the pathogenesis of gastric ulcer. The aim of the present study was to investigate the anti‐inflammatory and anti‐ulcerogenic effects of C‐phycocyanin against ethanol‐induced gastric ulcer targeting HMGB1/NLRP3/NF‐κB pathway. Ulcer induction showed increase in HMGB1 expression through activation of nucleotide‐binding domain and leucine‐rich repeat‐containing protein 3 (NLRP3) inflammasome and nuclear factor kappa p65 (NF‐κB p65). Moreover, oxidative stress and inflammatory markers were elevated in the ulcer‐treated grou...

Research paper thumbnail of Contrast media (meglumine diatrizoate) aggravates renal inflammation, oxidative DNA damage and apoptosis in diabetic rats which is restored by sulforaphane through Nrf2/HO-1 reactivation

Chemico-Biological Interactions, 2019

Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contr... more Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contrast media. It doubles the risk and decreases survival rate of contrast induced nephropathy (CIN). Sulforaphane has antioxidant properties via Nrf2 activation. The interaction of diabetes and/or sulforaphane with contrast media on Nrf2 regulation is not yet understood. Herein, diabetes was induced by a single intra-peritoneal injection of streptozotocin. Animals were then divided into five groups; control non-diabetic group; diabetic group; diabetic/sulforaphane group; diabetic/CIN group; diabetic/CIN/sulforaphane group. Animals were assessed 24 h after CIN induction. Sulforaphane improved the impaired nephrotoxicity parameters, histopathological features, and oxidative stress markers induced by contrast media (meglumine diatrizoate) in diabetic rats. Immunofluorescence detection revealed increased Nrf2 expression in kidney sections after sulforaphane pretreatment. Moreover, gene expression of Nrf2 and HO-1 were up-regulated, while IL-6 and caspase3 were down-regulated in kidney tissues of animals pretreated with sulforaphane. In NRK-52E cells, sulforaphane pretreatment significantly ameliorated the cytotoxicity of meglumine diatrizoate. However, silencing Nrf2 using small interfering RNA (siRNA) abolished the cytoprotective effects of sulforaphane. Collectively, the results of this study suggest that Nrf2/HO-1 pathway has a protective role against CIN and support the clinical implication of Nrf2 activators, such as sulforaphane, in CIN particularly in diabetic patients.

Research paper thumbnail of Comparative Study on the Influence of Cocoa And/Or Vinpocetine Against Development of Alzheimer’s Disease in Rats: Focus on Social Isolation Associated with Disease Progression

Alzheimer's & Dementia, 2017

Research paper thumbnail of Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways

Biomedicine & Pharmacotherapy, 2019

Metformin is one of the most commonly prescribed antidiabetic drugs. A recent clinical study has ... more Metformin is one of the most commonly prescribed antidiabetic drugs. A recent clinical study has highlighted the protective role of metformin against cardiac complications in type I diabetes. Curcumin is a natural compound with well-known antioxidant and anti-inflammatory properties. The present study was designed to investigate the possible role of curcumin in potentiating metformin`s putative effects. Rats received single injection of 52.5 mg/kg streptozocin and the diabetic rats were treated with metformin (200 mg/kg/day), curcumin (100 mg/kg/day) and their combination for 6 weeks. Diabetic rats showed degenerated myocardium as well as significant increase in Creatine Kinase-MB (CK-MB), troponin I and TGF-β 1 levels. In addition, cardiac levels of lipid peroxidation, IL-6, and NF-κB were significantly elevated. Although treatment with metformin restored most of the measured parameters, it showed insignificant improvement in histopathological architecture accompanied by absence of antioxidant effect. Interestingly, concomitant administration of curcumin along with metformin revealed more protection than metformin alone. Inhibition of JAK/STAT pathway and activation of Nrf2/HO-1 pathway seems to be among the mechanisms mediating the effects of curcumin and metformin. The findings of this study highlight the benefits of metformin/curcumin combination in preventing diabetic cardiomyopathy.

Research paper thumbnail of Cytoglobin has potent superoxide dismutase function

Proceedings of the National Academy of Sciences, 2021

Significance We identified a novel function of cytoglobin (Cygb) as an efficient superoxide dismu... more Significance We identified a novel function of cytoglobin (Cygb) as an efficient superoxide dismutase (SOD) with a high–bimolecular dismutation rate on the order of 10 8 M −1 ⋅ s −1 . It is the first Fe-centered SOD identified in mammalian cells and the only member of the globin family shown to have potent SOD activity. This SOD function of Cygb may serve to explain the prior reports of its antioxidative activity and the toxicities and disease seen with its genetic deletion, including the increased incidence of tumors. Combined with its potent NO dioxygenase activity, Cygb would be highly effective in decreasing both O 2 •− and NO levels, serving to decrease the formation of peroxynitrite and secondary oxidative injury.

Research paper thumbnail of Electronic Cigarette Exposure Induces Vascular Endothelial Dysfunction with NADPH Oxidase Activation and eNOS Uncoupling

Research paper thumbnail of Figure-5_PNAS

Figure 5 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 5 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-4_PNAS

Figure 4 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 4 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 file for Figure 4 is included.<br>

Research paper thumbnail of Figure-2_PNAS

Figure 2 of PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The Sigma... more Figure 2 of PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel of the figure are included.<br>

Research paper thumbnail of Figure-1_PNAS

Figure 1 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function.<br... more Figure 1 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function.<br>

Research paper thumbnail of Figure-7_PNAS

Figure 7 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 7 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-6_PNAS

Figure 6 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 6 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-9_PNAS

Figure 9 of the PNAS article: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot ... more Figure 9 of the PNAS article: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot files for each of the panels are included. The image file of the gel in Panel A is also included.<br>

Research paper thumbnail of Figure-8_PNAS

Figure 8 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 8 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 files for each panel are included.<br>

Research paper thumbnail of Figure-3_PNAS

Figure 3 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The S... more Figure 3 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The SigmaPlot 13 file for each panel of the figure is included.<br>

Research paper thumbnail of Figure-10_PNAS

Figure 10 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The ... more Figure 10 of the PNAS article entitled: Cytoglobin Has Potent Superoxide Dismutase Function. The PowerPoint file of the figure build and the GraphPad Prism file of the bar graph are included.<br>

Research paper thumbnail of Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling

American Journal of Physiology-Heart and Circulatory Physiology, 2022

Underlying mechanisms of e-cig-induced vascular endothelial dysfunction are delineated. e-cig exp... more Underlying mechanisms of e-cig-induced vascular endothelial dysfunction are delineated. e-cig exposure activates and increases expression of NADPH oxidase and disrupts activation and coupling of eNOS, leading to a vicious cycle of superoxide generation and peroxynitrite formation, with tetrahydrobiopterin depletion, causing loss of NO that triggers vascular endothelial dysfunction. This process is progressive, increasing with the duration of e-cig exposure, and is more severe in the presence of nicotine, but observed even with nicotine-free vaping.

Research paper thumbnail of Mechanism of NO Decay in Vascular Smooth Muscle Cells: Role of Cytoglobin and Identification of its Cellular Reducing System

Research paper thumbnail of Role of cytoglobin in cigarette smoke constituent-induced loss of nitric oxide bioavailability in vascular smooth muscle cells

Nitric Oxide, 2021

Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vasc... more Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vascular smooth muscle cells (VSMCs) and is crucial for the regulation of vascular tone. In the presence of its requisite cytochrome B5a (B5)/ B5 reductase-isoform-3 (B5R) reducing system, Cygb controls NO metabolism through the oxygen-dependent process of NO dioxygenation. Tobacco cigarette smoking (TCS) induces vascular dysfunction; however, the role of Cygb in the pathophysiology of TCS-induced cardiovascular disease has not been previously investigated. While TCS impairs NO biosynthesis, its effect on NO metabolism remains unclear. Therefore, we performed studies in aortic VSMCs with tobacco smoke extract (TSE) exposure to investigate the effects of cigarette smoke constituents on the rates of NO decay, with focus on the alterations that occur in the process of Cygb-mediated NO metabolism. TSE greatly enhanced the rates of NO metabolism by VSMCs. An initial increase in superoxide-mediated NO degradation was seen at 4 hours of exposure. This was followed by much larger progressive increases at 24 and 48 hours, accompanied by parallel increases in the expression of Cygb and B5/B5R. siRNA-mediated Cygb knockdown greatly decreased these TSE-induced elevations in NO decay rates. Therefore, upregulation of the levels of Cygb and its reducing system accounted for the large increase in NO metabolism rate seen after 24 hours of TSE exposure. Thus, increased Cygb-mediated NO degradation would contribute to TCS-induced vascular dysfunction and partial inhibition of Cygb expression or its NO dioxygenase function could be a promising therapeutic target to prevent secondary cardiovascular disease.

Research paper thumbnail of Defining the reducing system of the NO dioxygenase cytoglobin in vascular smooth muscle cells and its critical role in regulating cellular NO decay

Journal of Biological Chemistry, 2021

In smooth muscle, cytoglobin (Cygb) functions as a potent nitric oxide (NO) dioxygenase and regul... more In smooth muscle, cytoglobin (Cygb) functions as a potent nitric oxide (NO) dioxygenase and regulates NO metabolism and vascular tone. Major questions remain regarding which cellular reducing systems regulate Cygb-mediated NO metabolism. To better define the Cygb-mediated NO dioxygenation process in vascular smooth muscle cells (SMCs), and the requisite reducing systems that regulate cellular NO decay, we assessed the intracellular concentrations of Cygb and its putative reducing systems and examined their roles in the process of NO decay. Cygb and the reducing systems, cytochrome b5 (B5)/cytochrome b5 reductase (B5R) and cytochrome P450 reductase (CPR) were measured in aortic SMCs. Intracellular Cygb concentration was estimated as 3.5 μM, while B5R, B5, and CPR were 0.88, 0.38, and 0.15 μM, respectively. NO decay in SMCs was measured following bolus addition of NO to air-equilibrated cells. siRNA-mediated knockdown experiments indicated that ∼78% of NO metabolism in SMCs is Cygb-dependent. Of this, ∼87% was B5R- and B5-dependent. CPR knockdown resulted in a small decrease in the NO dioxygenation rate (VNO), while depletion of ascorbate had no effect. Kinetic analysis of VNO for the B5/B5R/Cygb system with variation of B5 or B5R concentrations from their SMC levels showed that VNO exhibits apparent Michaelis–Menten behavior for B5 and B5R. In contrast, linear variation was seen with change in Cygb concentration. Overall, B5/B5R was demonstrated to be the major reducing system supporting Cygb-mediated NO metabolism in SMCs with changes in cellular B5/B5R levels modulating the process of NO decay.

Research paper thumbnail of C‐phycocyanin protects against ethanol‐induced gastric ulcers in rats: Role of HMGB1/NLRP3/NF‐κB pathway

Basic & Clinical Pharmacology & Toxicology, 2020

Gastric ulcer is a widespread inflammatory disease with high socio‐economic burden. C‐phycocyanin... more Gastric ulcer is a widespread inflammatory disease with high socio‐economic burden. C‐phycocyanin is one of the active constituents of Spirulina microalgae, and although it is well known for its antioxidant and anti‐inflammatory properties, its protective effects against gastric ulcer have not yet been identified. High‐mobility group box 1 (HMGB1) is a nuclear protein that, once secreted extracellularly, initiates several inflammatory reactions, and it is involved in the pathogenesis of gastric ulcer. The aim of the present study was to investigate the anti‐inflammatory and anti‐ulcerogenic effects of C‐phycocyanin against ethanol‐induced gastric ulcer targeting HMGB1/NLRP3/NF‐κB pathway. Ulcer induction showed increase in HMGB1 expression through activation of nucleotide‐binding domain and leucine‐rich repeat‐containing protein 3 (NLRP3) inflammasome and nuclear factor kappa p65 (NF‐κB p65). Moreover, oxidative stress and inflammatory markers were elevated in the ulcer‐treated grou...

Research paper thumbnail of Contrast media (meglumine diatrizoate) aggravates renal inflammation, oxidative DNA damage and apoptosis in diabetic rats which is restored by sulforaphane through Nrf2/HO-1 reactivation

Chemico-Biological Interactions, 2019

Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contr... more Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contrast media. It doubles the risk and decreases survival rate of contrast induced nephropathy (CIN). Sulforaphane has antioxidant properties via Nrf2 activation. The interaction of diabetes and/or sulforaphane with contrast media on Nrf2 regulation is not yet understood. Herein, diabetes was induced by a single intra-peritoneal injection of streptozotocin. Animals were then divided into five groups; control non-diabetic group; diabetic group; diabetic/sulforaphane group; diabetic/CIN group; diabetic/CIN/sulforaphane group. Animals were assessed 24 h after CIN induction. Sulforaphane improved the impaired nephrotoxicity parameters, histopathological features, and oxidative stress markers induced by contrast media (meglumine diatrizoate) in diabetic rats. Immunofluorescence detection revealed increased Nrf2 expression in kidney sections after sulforaphane pretreatment. Moreover, gene expression of Nrf2 and HO-1 were up-regulated, while IL-6 and caspase3 were down-regulated in kidney tissues of animals pretreated with sulforaphane. In NRK-52E cells, sulforaphane pretreatment significantly ameliorated the cytotoxicity of meglumine diatrizoate. However, silencing Nrf2 using small interfering RNA (siRNA) abolished the cytoprotective effects of sulforaphane. Collectively, the results of this study suggest that Nrf2/HO-1 pathway has a protective role against CIN and support the clinical implication of Nrf2 activators, such as sulforaphane, in CIN particularly in diabetic patients.

Research paper thumbnail of Comparative Study on the Influence of Cocoa And/Or Vinpocetine Against Development of Alzheimer’s Disease in Rats: Focus on Social Isolation Associated with Disease Progression

Alzheimer's & Dementia, 2017

Research paper thumbnail of Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways

Biomedicine & Pharmacotherapy, 2019

Metformin is one of the most commonly prescribed antidiabetic drugs. A recent clinical study has ... more Metformin is one of the most commonly prescribed antidiabetic drugs. A recent clinical study has highlighted the protective role of metformin against cardiac complications in type I diabetes. Curcumin is a natural compound with well-known antioxidant and anti-inflammatory properties. The present study was designed to investigate the possible role of curcumin in potentiating metformin`s putative effects. Rats received single injection of 52.5 mg/kg streptozocin and the diabetic rats were treated with metformin (200 mg/kg/day), curcumin (100 mg/kg/day) and their combination for 6 weeks. Diabetic rats showed degenerated myocardium as well as significant increase in Creatine Kinase-MB (CK-MB), troponin I and TGF-β 1 levels. In addition, cardiac levels of lipid peroxidation, IL-6, and NF-κB were significantly elevated. Although treatment with metformin restored most of the measured parameters, it showed insignificant improvement in histopathological architecture accompanied by absence of antioxidant effect. Interestingly, concomitant administration of curcumin along with metformin revealed more protection than metformin alone. Inhibition of JAK/STAT pathway and activation of Nrf2/HO-1 pathway seems to be among the mechanisms mediating the effects of curcumin and metformin. The findings of this study highlight the benefits of metformin/curcumin combination in preventing diabetic cardiomyopathy.