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Mitigation of dexamethasone-induced nephrotoxicity by modulating the activity of adrenergic receptors: Implication of Wnt/β-arrestin2/ β-catenin pathway
Faculty
Medicine
Year:
2022
Type of Publication:
ZU Hosted
Pages:
Authors:
Rasha Mohamed Sabry
Staff Zu Site
Abstract In Staff Site
Journal:
Life Sciences elsevier
Volume:
Keywords :
Mitigation , dexamethasone-induced nephrotoxicity , modulating , activity , adrenergic
Abstract:
The present study aimed to investigate the role of α and β-adrenergic receptors (βARs) in mediation or modulation of the dexamethasone-induced nephrotoxicity by using different pharmacological interventions. Nephrotoxicity was induced by subcutaneous injection of dexamethasone (10 mg/kg) for 7 days in Wistar albino rats. Eight groups were used: control; dexamethasone; carvedilol; phenylephrine; carvedilol and phenylephrine; propranolol; doxazosin; propranolol and doxazosin. At the end of experiment, rats were euthanized and blood, urine and kidney samples were collected. Serum and urinary creatinine and urinary total protein levels were measured. Also, the renal tissue levels of diacylglycerol (DAG); Akt kinase activity, malondialdehyde (MDA), NADPH oxidase 2 (NOX2), transforming growth factor-β (TGF-β), Wnt3A and β-catenin were recorded. Furthermore, histopathological and β-arrestin2-immunohistochemical examinations of renal tissues were performed. Results: Dexamethasone induced glomerular damage, proteinuria, renal oxidative stress and upregulated the renal Wnt/β-arrestin2/β-catenin pathway and the profibrotic signals. Blocking the α1 and βARs by carvedilol reduced the dexamethasone-induced nephrotoxicity. Pre-injection of phenylephrine did not reduce the reno- protective action of carvedilol. Blocking the βARs only by propranolol reduced the dexamethasone-induced nephrotoxicity to the same extent of carvedilol group. Blocking the α1ARs only by doxazosin reduced dexamethasone-induced nephrotoxicity to a higher extent than other treatments. However, combined use of propranolol and doxazosin did not synergize the reno-protective effects of doxazosin. Conclusion: Dexamethasone induces nephrotoxicity, possibly, by upregulating the Wnt/β-arrestin2/β-catenin pathway. Blocking either α1ARs or βARs can effectively protect against the dexamethasone-induced nephrotoxicity. However, combined blocking of α1ARs and βARs does not synergize the reno-protective effects.
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Rasha Mohamed Sabry, "Efficacy of olibanum and propolis medicinal extracts versus metronidazole in Giardia lamblia experimentally infected mice", zagazig university, 2020
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Rasha Mohamed Sabry, "Protective Effect of Date Palm Fruits (Phoenix Dactylifera L.) versus Vitamin C Against Mobile Phone Radiation-induced Pituitary Gland Damage in Rats", Zagazig University, 2022
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Rasha Mohamed Sabry, "Metabolite Profiling of Date Palm Fruit (Phoenix dactylifera L.) And Its Cytoprotective Effects Versus Vitamin C Against Mobile Phone Radiation-Induced Adrenal Gland Damage In Rats", zagazig university, 2022
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Rasha Mohamed Sabry, "Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats", -scielo, 2021
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Department Related Publications
Rasha Mohamed Sabry, "Efficacy of olibanum and propolis medicinal extracts versus metronidazole in Giardia lamblia experimentally infected mice", zagazig university, 2020
More
Rasha Mohamed Sabry, "Protective Effect of Date Palm Fruits (Phoenix Dactylifera L.) versus Vitamin C Against Mobile Phone Radiation-induced Pituitary Gland Damage in Rats", Zagazig University, 2022
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Rasha Mohamed Sabry, "Metabolite Profiling of Date Palm Fruit (Phoenix dactylifera L.) And Its Cytoprotective Effects Versus Vitamin C Against Mobile Phone Radiation-Induced Adrenal Gland Damage In Rats", zagazig university, 2022
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Rasha Mohamed Sabry, "Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats", -scielo, 2021
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Eman Ahmed Ibrahim Mohamed Abdou, "Effect of Portulaca Oleracea Extract and Its Interactions with Propranolol in Cirrhotic Portal Hypertensive Rats", Tobacoo regulatory science, 2022
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