Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats

Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the imp...

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Main Authors: Mayada R. Farag, Attia A. A. Moselhy, Amany El-Mleeh, Samira H. Aljuaydi, Tamer Ahmed Ismail, Alessandro Di Cerbo, Giuseppe Crescenzo, Shimaa M. Abou-Zeid
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/10/12/1906
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author Mayada R. Farag
Attia A. A. Moselhy
Amany El-Mleeh
Samira H. Aljuaydi
Tamer Ahmed Ismail
Alessandro Di Cerbo
Giuseppe Crescenzo
Shimaa M. Abou-Zeid
author_facet Mayada R. Farag
Attia A. A. Moselhy
Amany El-Mleeh
Samira H. Aljuaydi
Tamer Ahmed Ismail
Alessandro Di Cerbo
Giuseppe Crescenzo
Shimaa M. Abou-Zeid
author_sort Mayada R. Farag
collection DOAJ
description Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.
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spelling doaj.art-461b6be51fda4579b04f75b5106b84932023-11-23T03:32:44ZengMDPI AGAntioxidants2076-39212021-11-011012190610.3390/antiox10121906Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in RatsMayada R. Farag0Attia A. A. Moselhy1Amany El-Mleeh2Samira H. Aljuaydi3Tamer Ahmed Ismail4Alessandro Di Cerbo5Giuseppe Crescenzo6Shimaa M. Abou-Zeid7Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Menoufia University, Shebin Elkoum 32511, EgyptDepartment of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, EgyptDepartment of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaSchool of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, ItalyDepartment of Veterinary Medicine, University of Bari ‘Aldo Moro’, 70121 Bari, ItalyDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 6012201, EgyptDoxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.https://www.mdpi.com/2076-3921/10/12/1906doxorubicinquercetinimmunoglobulinsapoptosisspleencytokines
spellingShingle Mayada R. Farag
Attia A. A. Moselhy
Amany El-Mleeh
Samira H. Aljuaydi
Tamer Ahmed Ismail
Alessandro Di Cerbo
Giuseppe Crescenzo
Shimaa M. Abou-Zeid
Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
Antioxidants
doxorubicin
quercetin
immunoglobulins
apoptosis
spleen
cytokines
title Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
title_full Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
title_fullStr Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
title_full_unstemmed Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
title_short Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats
title_sort quercetin alleviates the immunotoxic impact mediated by oxidative stress and inflammation induced by doxorubicin exposure in rats
topic doxorubicin
quercetin
immunoglobulins
apoptosis
spleen
cytokines
url https://www.mdpi.com/2076-3921/10/12/1906
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