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

Mayada R. Farag,Shimaa M. Abou-Zeid,Amany El-Mleeh,Tamer Ahmed Ismail,Attia A. A. Moselhy,Alessandro Di Cerbo,Giuseppe Crescenzo,Samira H. Aljuaydi

doi:10.3390/antiox10121906

Abstract

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.

Highlights

Doxorubicin (DOX) is an anthracycline antibiotic with broad-spectrum and potent anti-neoplastic activity
Our findings revealed a decline in red blood cells (RBCs) count, hemoglobin level, packed cell volume (PCV)%, mean corpuscular volume (MCV), and in DOX-treated rats.of
Of DOX as a chemotherapeutic drug against various types of cancer. The results of this the increased rate of RBC destruction may contribute to the anemic condition, as RBCs are study provide evidence about the protective effects of QUR on DOX‐induced immuno‐

Summary

Introduction

Doxorubicin (DOX) is an anthracycline antibiotic with broad-spectrum and potent anti-neoplastic activity. It is used either alone or combined with other chemotherapeutic drugs as the frontline therapy for a wide variety of solid tumors such as breast, urogenital, Antioxidants 2021, 10, 1906. DOX was reported to increase the production of reactive oxygen species (ROS), which may overwhelm the enzymatic antioxidants and total sulfhydryl levels present in tissues. Like other anticancer drugs, DOX cannot distinguish between malignant and normal cells, so that it non-selectively induces deleterious effects in healthy tissues such as oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction [1], which limit the clinical utility of the drug. Aside from cardiomyopathy, the cellular elements responsible for eliciting immune responses are affected, causing immunosuppression with increased possibility of microbial infection and wound healing delay [4,5]

Objectives

Methods

Discussion

Conclusion