Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators

In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the...

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Main Authors: Eman A. Abdelghffar, Wael A. Obaid, Zuhair M. Mohammedsaleh, Wafae Ouchari, Omayma A. Eldahshan, Mansour Sobeh
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332222012252
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author Eman A. Abdelghffar
Wael A. Obaid
Zuhair M. Mohammedsaleh
Wafae Ouchari
Omayma A. Eldahshan
Mansour Sobeh
author_facet Eman A. Abdelghffar
Wael A. Obaid
Zuhair M. Mohammedsaleh
Wafae Ouchari
Omayma A. Eldahshan
Mansour Sobeh
author_sort Eman A. Abdelghffar
collection DOAJ
description In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the possible mitigative effects of Ajwa dates fruits extract (ADFE) vs CP-induced nephrotoxicity in rats, in addition to phytochemical profiling of its components via LC-MS/MS. Six groups were formed from forty-two male rats. G1: control, G2: ADFE 0.25 g/kg, G3: ADFE 0.5 g/kg (for 21 days), G4: CP -intoxicated group (single i.p. dose of 7.0 mg/kg b.w) on day 16th, G5: ADFE 0.25 + CP, G6: ADFE 0.5 + CP. LC-MS/MS analysis revealed the tentative identification of 17 compounds of different chemical nature, including organic/phenolic acids, and flavonoids and their sulphated/glycosides derivatives. ADFE has considerable antioxidant potential (DPPH with IC50 326.65 µg/ml and FRAP= 20.91 mM FeSO4/g extract) and total phenolic content (TPC = 35.44 mg/GAE/g extract). It (especially at dose 0.5 g/kg b.w) significantly modulated the toxicity of CP via enhancing food intake and hematobiochemical indices (renal functions, anemia, and leucopenia), increasing the renal antioxidant status (GSH, SOD, and CAT), decreasing the production of oxidative stress and inflammatory markers (MDA, NO, H2O2, MPO, MCP-1, TNF-α and IL-6), augmenting mRNA expression of Nrf2, and modulating NOX4 mRNA expression. The existence of bioactive compounds in ADFE may be responsible for their prophylactic properties, demonstrating natural usefulness in the treatment of oxidative stress, hypochromic anemia, immunodeficiency, and inflammatory complications, all of which are chemotherapy side effects.
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spelling doaj.art-5b70f7f26f1f4695bfa5fb20ec36bec62022-12-22T04:14:01ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113836Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediatorsEman A. Abdelghffar0Wael A. Obaid1Zuhair M. Mohammedsaleh2Wafae Ouchari3Omayma A. Eldahshan4Mansour Sobeh5Biology Department, College of Science, Taibah University, Saudi Arabia; Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt; Corresponding author at: Biology Department, College of Science, Taibah University, Saudi Arabia.Biology Department, College of Science, Taibah University, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Saudi ArabiaAgroBioSciences, Mohammed VI Polytechnic University, Lot 660-Hay MoulayRachid, Ben-Guerir 43150, MoroccoPharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptAgroBioSciences, Mohammed VI Polytechnic University, Lot 660-Hay MoulayRachid, Ben-Guerir 43150, Morocco; Corresponding author.In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the possible mitigative effects of Ajwa dates fruits extract (ADFE) vs CP-induced nephrotoxicity in rats, in addition to phytochemical profiling of its components via LC-MS/MS. Six groups were formed from forty-two male rats. G1: control, G2: ADFE 0.25 g/kg, G3: ADFE 0.5 g/kg (for 21 days), G4: CP -intoxicated group (single i.p. dose of 7.0 mg/kg b.w) on day 16th, G5: ADFE 0.25 + CP, G6: ADFE 0.5 + CP. LC-MS/MS analysis revealed the tentative identification of 17 compounds of different chemical nature, including organic/phenolic acids, and flavonoids and their sulphated/glycosides derivatives. ADFE has considerable antioxidant potential (DPPH with IC50 326.65 µg/ml and FRAP= 20.91 mM FeSO4/g extract) and total phenolic content (TPC = 35.44 mg/GAE/g extract). It (especially at dose 0.5 g/kg b.w) significantly modulated the toxicity of CP via enhancing food intake and hematobiochemical indices (renal functions, anemia, and leucopenia), increasing the renal antioxidant status (GSH, SOD, and CAT), decreasing the production of oxidative stress and inflammatory markers (MDA, NO, H2O2, MPO, MCP-1, TNF-α and IL-6), augmenting mRNA expression of Nrf2, and modulating NOX4 mRNA expression. The existence of bioactive compounds in ADFE may be responsible for their prophylactic properties, demonstrating natural usefulness in the treatment of oxidative stress, hypochromic anemia, immunodeficiency, and inflammatory complications, all of which are chemotherapy side effects.http://www.sciencedirect.com/science/article/pii/S0753332222012252Phoenix dactyliferaAjwa datesLC-MS/MSAntioxidantAnti-inflammatory Nephroprotective
spellingShingle Eman A. Abdelghffar
Wael A. Obaid
Zuhair M. Mohammedsaleh
Wafae Ouchari
Omayma A. Eldahshan
Mansour Sobeh
Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
Biomedicine & Pharmacotherapy
Phoenix dactylifera
Ajwa dates
LC-MS/MS
Antioxidant
Anti-inflammatory Nephroprotective
title Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
title_full Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
title_fullStr Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
title_full_unstemmed Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
title_short Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators
title_sort ajwa dates phoenix dactylifera l attenuate cisplatin induced nephrotoxicity in rats via augmenting nrf2 modulating nadph oxidase 4 and mitigating inflammatory apoptotic mediators
topic Phoenix dactylifera
Ajwa dates
LC-MS/MS
Antioxidant
Anti-inflammatory Nephroprotective
url http://www.sciencedirect.com/science/article/pii/S0753332222012252
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