Ashraf Taye

Publications of Ashraf Taye

• The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-α and free fatty acids.

  Authors: Mohamed A El-Moselhy, Ashraf Taye, Sara Shaaban Sharkawi, Suzan F I El-Sisi, Ahmed Fahmy Ahmed

  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 02/2011; 49(5):1129-40.

  This study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitusThis study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitus (T2DM) and the mechanisms underlying this effect. Insulin resistance and T2DM was induced in male Sprague Dawley rats by high fat diet (HFD) feeding for 60 and for 75 days representing two regimens of the study, protection and treatment. Prophylactic oral administration of curcumin (80 mg/kg), rosiglitazone (1 mg/kg), their combination, or vehicle (in control groups) was started along with HFD feeding in different groups. Treatment is achieved by oral administration of the previously mentioned agents in the last 15 days of HFD feeding after induction of insulin resistance and T2DM in rats. Curcumin showed an anti-hyperglycemic effect and improved insulin sensitivity, and this action may be attributed at least in part to its anti-inflammatory properties as evident by attenuating TNF-α levels in HFD fed rats, and its anti-lipolytic effect as evident by attenuating plasma free fatty acids. The curcumin effects are comparable to those of rosiglitazone, which indicate that they may act similarly. Finally we can say that, curcumin could be a beneficial adjuvant therapy in patients with T2DM.

• Oxidative stress and endothelial dysfunction in aortas of aged spontaneously hypertensive rats by NOX1/2 is reversed by NADPH oxidase inhibition.

  Authors: Sven Wind, Knut Beuerlein, Melanie E Armitage, Ashraf Taye, Arun H S Kumar, Daniel Janowitz, Christina Neff, Ajay M Shah, Kirstin Wingler, Harald H H W Schmidt

  Hypertension. 09/2010; 56(3):490-7.

  Arterial hypertension is associated with increased levels of reactive oxygen species, which may scavenge endothelium-derived NO and thereby diminish its vasorelaxant effects. However, theArterial hypertension is associated with increased levels of reactive oxygen species, which may scavenge endothelium-derived NO and thereby diminish its vasorelaxant effects. However, the quantitatively relevant source of reactive oxygen species is unclear. Thus, this potential pathomechanism is not yet pharmacologically targetable. Several enzymatic sources of reactive oxygen species have been suggested: uncoupled endothelial NO synthase, xanthine oxidase, and NADPH oxidases. Here we show that increased reactive oxygen species formation in aortas of 12- to 14-month-old spontaneously hypertensive rats versus age-matched Wistar Kyoto rats is inhibited by the specific NADPH oxidase inhibitor VAS2870 but neither by the xanthine oxidase inhibitor oxypurinol nor the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester. NADPH oxidase activity, as well as protein expression of its catalytic subunits, NOX1 and NOX2, was increased in the aortas of spontaneously hypertensive rats, whereas the expression of NOX4 protein, the most abundant NOX isoform, was not significantly changed. Impaired acetylcholine-induced relaxation of spontaneously hypertensive rat aortas was significantly improved by VAS2870. In conclusion, NOX1 and NOX2 but not NOX4 proteins are increased in aged spontaneously hypertensive rat aortas. Importantly, these NOX isoforms, in particular, ectopic expression of NOX1 in endothelial cells, appear to affect vascular function in an NADPH oxidase inhibitor-reversible manner. NADPH oxidases may, thus, be a novel target for the treatment of systemic hypertension.

• Green tea ameliorates renal oxidative damage induced by gentamicin in rats.

  Authors: Ihab T Abdel-Raheem, Gamal A El-Sherbiny, Ashraf Taye

  Pakistan journal of pharmaceutical sciences. 01/2010; 23(1):21-8.

  Recent studies indicate that free radicals are important mediators of renal damage induced by gentamicin (GM), an aminoglycoside antibiotic widely used in treating severe gram-negative infections.Recent studies indicate that free radicals are important mediators of renal damage induced by gentamicin (GM), an aminoglycoside antibiotic widely used in treating severe gram-negative infections. Green tea extract (GTE) was reported to have antioxidant and free radical scavenging activities. Therefore, the aim of this work was to investigate the possible protective effect of GTE against gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. Group-1 (control) received normal saline. Group-2 received GTE (300 mg/kg/d, orally). Group-3 received gentamicin (80 mg/kg/d, intraperitoneally). Group-4 was injected with GTE plus gentamicin simultaneously. Daily urinary total protein levels were estimated to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide expressed as thiobarbituric acid reactive substance (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM produced elevation in urinary total protein, BUN, serum creatinine and TBARS levels. On the other hand, GM reduced the GSH level and SOD, CAT activities. The simultaneous administration of GTE plus gentamicin protected kidney tissues against nephrotoxic effect of gentamicin as evidenced from amelioration of histopathological alterations and normalization of kidney biochemical parameters.

• Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose.

  Authors: Ashraf Taye, Adel H Saad, Arun Hs Kumar, Henning Morawietz

  European journal of pharmacology. 10/2009;

  Hyperglycemia-induced generation of reactive oxygen species contributes to the development of proatherogenic changes and vasculopathy in diabetes. NADPH oxidase has been recognized as a major sourceHyperglycemia-induced generation of reactive oxygen species contributes to the development of proatherogenic changes and vasculopathy in diabetes. NADPH oxidase has been recognized as a major source of reactive oxygen species in the vasculature and the lectin-like oxLDL receptor-1 (LOX-1) appears to play a crucial role in the pathogenesis of diabetic endothelial dysfunction. The present study aimed to examine the relationships between the hyperglycemia-mediated NADPH oxidase-LOX-1 pathway activation and nitric oxide-mediated endothelial function. In addition, we investigated effect of the NADPH oxidase inhibitor, apocynin on these consequences. In human umbilical artery endothelial cells (HUAECs), the effect of high glucose on expressional regulations and functional consequences of NADPH oxidase subunits, LOX-1 and endothelial nitric oxide synthase (eNOS), in the absence and presence of apocynin (10micromol/l) were evaluated. HUAECs were cultured under normal (5.5mmol/l) or high glucose (30mmol/l) concentrations for 48h in the absence and presence of apocynin. Our results showed that high glucose significantly enhanced the activity and the protein expression of NADPH oxidase subunits, Nox2 and p47(phox). High glucose markedly increased LOX-1 mRNA level and this was functionally reflected on the augmented uptake of Dil-labelled LDL (5micromol/l, 3h) by HUAECs. Furthermore, high glucose attenuated eNOS protein and total nitrite levels. However, apocynin inhibited all these changes. Collectively, our study demonstrates that high glucose-induced oxidative stress via NADPH oxidase activation and this contributed to LOX-1 upregulation and eNOS downregulation in human endothelial cells. Apocynin efficiently reversed these consequences, suggesting its potential role as vasculoprotective agent.

• Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels.

  Authors: Johannes-Peter Stasch, Peter M Schmidt, Pavel I Nedvetsky, Tatiana Y Nedvetskaya, Arun Kumar H S, Sabine Meurer, Martin Deile, Ashraf Taye, Andreas Knorr, Harald Lapp, Helmut Müller, Yagmur Turgay, Christiane Rothkegel, Adrian Tersteegen, Barbara Kemp-Harper, Werner Müller-Esterl, Harald H H W Schmidt

  The Journal of clinical investigation. 10/2006; 116(9):2552-61.

  ROS are a risk factor of several cardiovascular disorders and interfere with NO/soluble guanylyl cyclase/cyclic GMP (NO/sGC/cGMP) signaling through scavenging of NO and formation of the strongROS are a risk factor of several cardiovascular disorders and interfere with NO/soluble guanylyl cyclase/cyclic GMP (NO/sGC/cGMP) signaling through scavenging of NO and formation of the strong oxidant peroxynitrite. Increased oxidative stress affects the heme-containing NO receptor sGC by both decreasing its expression levels and impairing NO-induced activation, making vasodilator therapy with NO donors less effective. Here we show in vivo that oxidative stress and related vascular disease states, including human diabetes mellitus, led to an sGC that was indistinguishable from the in vitro oxidized/heme-free enzyme. This sGC variant represents what we believe to be a novel cGMP signaling entity that is unresponsive to NO and prone to degradation. Whereas high-affinity ligands for the unoccupied heme pocket of sGC such as zinc-protoporphyrin IX and the novel NO-independent sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino) methyl [benzoic]acid (BAY 58-2667) stabilized the enzyme, only the latter activated the NO-insensitive sGC variant. Importantly, in isolated cells, in blood vessels, and in vivo, BAY 58-2667 was more effective and potentiated under pathophysiological and oxidative stress conditions. This therapeutic principle preferentially dilates diseased versus normal blood vessels and may have far-reaching implications for the currently investigated clinical use of BAY 58-2667 as a unique diagnostic tool and highly innovative vascular therapy.

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• Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats.

  Authors: Gamal A El-Sherbiny, Ashraf Taye, Ihab T Abdel-Raheem

  Annals of hepatology : official journal of the Mexican Association of Hepatology. 8(2):134-40.

  Incidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remainsIncidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remains undefined. On the other hand, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant therapy in various liver diseases. Therefore, the present study was designed to elucidate the possible role of oxidative stress in hepatotoxicity induced by Co-amoxyclav and the putative protective role of UDCA in rats. Effects of amoxicillin (Amox; 50 mg/kg, orally, 21 d) or clavulanic acid (Clav; 10 mg/kg, orally, 21 d) and their combined administration on the biochemical liver parameters, reduced glutathione (GSH), lipid peroxidation measured as hepatic malondialdehyde (MDA) levels. In addition, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) production in liver homogenate were also evaluated. On the other hand, the protective effects of pretreatment with UDCA (20 mg/kg, orally, 21 d) on these parameters were also evaluated. Our results show that pretreatment with UDCA reduced the liver parameters that were enhanced by single or combined administration of Amox and/or Clav such as serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum bilirubin levels. Moreover, pretreatment with UDCA normalized the GSH level and inhibited the elevation in hepatic MDA concentration. The enhanced MPO activity and ROS production in liver homogenate of rats treated with Clav or Co-amoxyclav were also normalized by UDCA pretreatment. In conclusion, the present data suggest that UDCA acts as effective hepatoprotective agent against liver dysfunction caused by Co-amoxyclav and this effect is related to its antioxidant properties.

• Aldosterone augments LOX-1-mediated low-density lipoprotein uptake in human umbilical artery endothelial cells.

  Authors: Ashraf Taye, Tatsuya Sawamura, Henning Morawietz

  Pharmacological reports : PR. 62(2):311-8.

  Aldosterone and oxidized low-density lipoprotein (oxLDL) are recognized risk factors for cardiovascular disease and atherosclerosis. LOX-1 is a multi-ligand receptor originally identified as theAldosterone and oxidized low-density lipoprotein (oxLDL) are recognized risk factors for cardiovascular disease and atherosclerosis. LOX-1 is a multi-ligand receptor originally identified as the endothelial oxLDL receptor, which mediates the uptake of oxLDL and plays a role in early atherosclerosis. The present study aimed to investigate the pathophysiological relevance of LOX-1 in aldosterone-induced atherosclerosis. The effect of aldosterone on LOX-1 expression and LDL uptake in primary cultures of human umbilical artery endothelial cells (HUAECs) was investigated in the absence and presence of the mineralocorticoid receptor (MR) antagonist spironolactone (Spiro). Aldosterone increased both mRNA and protein expression of LOX-1 in a dose-dependent manner with a maximum effect reached 24 h after treatment. Increased LOX-1 expression was associated with an augmented uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-labeled LDL(5 muM/ml, 3h). However, pretreatment with Spiro (1 muM) almost reduced these effects. Additionally, an increase in MR expression was detected in response to aldosterone in HUAECs. Collectively, our study demonstrates that aldosterone promotes LOX-1-mediated LDL uptake in human endothelial cells, and Spiro effectively inhibited these effects, suggesting that MR inhibition may be considered as a new anti-atherosclerotic therapy.

• Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats.

  Authors: Ashraf Taye, Mohamed A El-Moselhy, Magdy K A Hassan, Hanaa M Ibrahim, Aliaa F Mohammed

  Annals of hepatology : official journal of the Mexican Association of Hepatology. 8(4):364-70.

  The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting.The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting. Moreover, we attempted to compare its effect to the well-established hepatoprotective agent, silymarin (SYM). The rats were randomly assigned 5 groups, control, PTX-treated (100 mg/kg, 3 weeks), SYM-treated (100 mg/kg, 3 weeks) and their combination. Hepatic injury was induced by intraperitoneal single dose injection of D-Gal (800 mg/kg). Hepatic functions parameters, including serum albumin and alkaline phosphatase (ALP) levels were determined. Antioxidants enzyme activities such as superoxide dismutase (SOD), catalase (CAT) as well as lipid peroxides and hepatic total nitrites were measured. Besides, histopathological examination was also performed using portions of liver tissues. Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents. Pretreatment with PTX prevented D-Gal-induced reduction of antioxidante enzyme activities, SOD and CAT, and attenuated the elevated malonaldahyde (MDA) level in hepatic tissue as marker of lipid peroxidation. In addition, pretreatment with PTX resulted in an increase in hepatic triglycerides, normalization of nitric oxide level, and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal. These biochemical changes were reflected on attenuation the structural alterations of the liver integrity. Collectively, our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties.