Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway

Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon p...

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Main Authors: Maysa A. Mobasher, Marwa T. Hassen, Rasha A. Ebiya, Norah A. Alturki, Ahmad Alzamami, Hanaa K. Mohamed, Nabil S. Awad, Dina Khodeer, Bosy A. Abd El-Motelp
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/28/1/122
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author Maysa A. Mobasher
Marwa T. Hassen
Rasha A. Ebiya
Norah A. Alturki
Ahmad Alzamami
Hanaa K. Mohamed
Nabil S. Awad
Dina Khodeer
Bosy A. Abd El-Motelp
author_facet Maysa A. Mobasher
Marwa T. Hassen
Rasha A. Ebiya
Norah A. Alturki
Ahmad Alzamami
Hanaa K. Mohamed
Nabil S. Awad
Dina Khodeer
Bosy A. Abd El-Motelp
author_sort Maysa A. Mobasher
collection DOAJ
description Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Moreover, CPA administration to rats significantly increased the serum level of Malondialdehyde (MDA) and significantly lowered the levels of reduced glutathione (GSH) and superoxide dismutase (SOD); in addition, it increased nuclear factor kappa B (NF-κB) levels, tumor necrosis factor-α (TNF-α), as well as cyclooxygenase 2 (COX-2) with the spread expression of inducible nitric oxide synthase (iNOS) mRNA levels and caspase-3 (Casp3) levels in ovarian tissues versus the control rats. However, treatment with LPE and RES suppressed the triggering of NF- κB pathways, evidenced by a considerable reduction in Casp3 & iNOS mRNA expression level and significant ameliorative effects in all evaluated parameters, as confirmed by the histological and immunohistochemical investigation when comparing the model group. In overall findings, both lemon peel extract and resveratrol can mitigate the adverse effects of CPA-induced POF. Most crucially, its combination therapy is a promising pharmacological agent for this disease.
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spelling doaj.art-121c6c9ded16474c830528b607c15c452023-12-03T14:56:43ZengMDPI AGMolecules1420-30492022-12-0128112210.3390/molecules28010122Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 PathwayMaysa A. Mobasher0Marwa T. Hassen1Rasha A. Ebiya2Norah A. Alturki3Ahmad Alzamami4Hanaa K. Mohamed5Nabil S. Awad6Dina Khodeer7Bosy A. Abd El-Motelp8Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, EgyptDepartment of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, EgyptClinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh 11433, Saudi ArabiaClinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, Al Quwaiiyah 11961, Saudi ArabiaDepartment of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, EgyptDepartment of Genetics, Faculty of Agriculture and Natural Resources, Aswan University, Aswan 81528, EgyptDepartment of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, EgyptPremature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Moreover, CPA administration to rats significantly increased the serum level of Malondialdehyde (MDA) and significantly lowered the levels of reduced glutathione (GSH) and superoxide dismutase (SOD); in addition, it increased nuclear factor kappa B (NF-κB) levels, tumor necrosis factor-α (TNF-α), as well as cyclooxygenase 2 (COX-2) with the spread expression of inducible nitric oxide synthase (iNOS) mRNA levels and caspase-3 (Casp3) levels in ovarian tissues versus the control rats. However, treatment with LPE and RES suppressed the triggering of NF- κB pathways, evidenced by a considerable reduction in Casp3 & iNOS mRNA expression level and significant ameliorative effects in all evaluated parameters, as confirmed by the histological and immunohistochemical investigation when comparing the model group. In overall findings, both lemon peel extract and resveratrol can mitigate the adverse effects of CPA-induced POF. Most crucially, its combination therapy is a promising pharmacological agent for this disease.https://www.mdpi.com/1420-3049/28/1/122cyclophosphamidelemon peel extractresveratrolpremature ovarian failureinflammatory markergene expression
spellingShingle Maysa A. Mobasher
Marwa T. Hassen
Rasha A. Ebiya
Norah A. Alturki
Ahmad Alzamami
Hanaa K. Mohamed
Nabil S. Awad
Dina Khodeer
Bosy A. Abd El-Motelp
Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
Molecules
cyclophosphamide
lemon peel extract
resveratrol
premature ovarian failure
inflammatory marker
gene expression
title Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
title_full Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
title_fullStr Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
title_full_unstemmed Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
title_short Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway
title_sort ameliorative effect of citrus lemon peel extract and resveratrol on premature ovarian failure rat model role of inos caspase 3 pathway
topic cyclophosphamide
lemon peel extract
resveratrol
premature ovarian failure
inflammatory marker
gene expression
url https://www.mdpi.com/1420-3049/28/1/122
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