Evaluation of The Effect of Fisetin against Cyclophosphamide-Induced Myelosuppression and Oxidative Stress in Male Albino Rats
DOI:
https://doi.org/10.31351/vol32iss2pp120-127Keywords:
Keywords: Fisetin, Cyclophosphamide, Myelosuppression, Oxidative StressAbstract
Myelosuppression is a serious disease that is related to the malfunction of blood cells production that leads to cytopenia which is the most serious hematologic toxicity of cancer chemotherapies including cyclophosphamide, which is a strong oxazaphosphorine [a nitrogen mustard alkylating agent] that can be used alone or combined with other chemotherapeutic agents for the treatment of different malignant diseases. It induces severe bone marrow suppression by damaging hematopoietic stem cells through the generation of oxidative stress. Fisetin is a hydrophobic polyphenolic compound with a wide range of pharmacological properties such as antioxidant, anti-inflammatory, antimicrobial, osteoprotective, antidiabetic, and anti-carcinogenic activities. The present study aims to evaluate the effects of fisetin alone and pretreatment with cyclophosphamide on some selected hematological and oxidative stress parameters in the male rats model. Animals were randomly divided into 4 groups each with 7 rats. The first group received 1% dimethyl sulfoxide (negative control group). The second group received oral fisetin. The third group received a single intraperitoneal (IP) injection of cyclophosphamide (CP) and the fourth group received fisetin for 7 constitutive days than a single IP injection of CP on day 7. Results showed that both fisetin and CP significantly reduced the total white blood cells and platelet counts compared to such counts in negative control/Group I (P<0.05) when each administered alone and in combination. Furthermore, results viewed that fisetin significantly increased GSH and SOD1, and decrease MDA levels in serum compared to such levels in CP (Group III) rats (P<0.05). The study concluded that the administration of fisetin alone causes leukopenia and thrombocytopenia and this decrease augmented in combination with CP; while exhibiting a strong antioxidant effect against CP induced-oxidative stress.
References
Brown D, Gatter K, Natkunam Y, Warnke R. Bone Marrow Diagnosis: An Illustrated Guide: Second Edition. Bone Marrow Diagnosis: An Illustrated Guide: Second Edition. John Wiley & Sons; 2007. 1–216 p.
Crea F, Giovannetti E, Zinzani PL, Danesi R. Pharmacologic rationale for early G-CSF prophylaxis in cancer patients and role of pharmacogenetics in treatment optimization. Crit Rev Oncol Hematol. 2009;72(1):21–44.
Ganusov V, Tomura M. Experimental and mathematical approaches to quantify recirculation kinetics of lymphocytes. bioRxiv 268326. DOI. 2018;10:268326.
Bronte V, Pittet MJ. The spleen in local and systemic regulation of immunity. Immunity. 2013;39(5):806–18.
Zhao A, Bin YU, Xian-Lin WU, Cao K-J, En-Qing LI, Qing-Mei LI, et al. Protective effects on myelosuppression mice treated by three different classic Chinese medicine formulae. Pharmacogn Mag. 2011;7(26):133.
Foubert J. Cancer-related anaemia and fatigue: assessment and treatment. Nurs Stand (through 2013). 2006;20(36):50.
Blackwell S, Crawford J. Filgrastim (r-metHuG-CSF) in the chemotherapy setting. Filgrastim Clin Pract New York Marcel Dekker, Inc. 1994;103–6.
Meotti FC, Forner S, Lima-Garcia JF, Viana AF, Calixto JB. Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia and urinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis. Chem Biol Interact. 2013;203(2):440–7.
Tripathi DN, Jena GB. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact. 2009;180(3):398–406.
Pérez-Jiménez J, Neveu V, Vos F, Scalbert A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr. 2010;64(3):S112–20.
Adhami VM, Syed DN, Khan N, Mukhtar H. Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management. Biochem Pharmacol. 2012;84(10):1277–81.
Antika LD, Dewi RM. Pharmacological aspects of fisetin. Asian Pac J Trop Biomed. 2021;11(1):1.
Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151–62.
Inkielewicz-Stepniak I, Radomski MW, Wozniak M. Fisetin prevents fluoride-and dexamethasone-induced oxidative damage in osteoblast and hippocampal cells. Food Chem Toxicol. 2012;50(3–4):583–9.
Sari EN, Soysal Y. Molecular and Therapeutic Effects of Fisetin Flavonoid in Diseases. J Basic Clin Heal Sci. 2020;4(3):190–6.
Ghanim WK. Evaluating the Effects of Different Doses of Vitamin B2 and Single Dose of Vitamin B12 Against Myelosuppression Induced by Cyclophosphamide in Experimental Rats. Iraqi J Pharm Sci (P-ISSN 1683-3597, E-ISSN 2521-3512). 2020;29(1):134–42.
Scoffin K. Hematology Analyzers-From Complete Blood Counts to Cell Morphology. Am Lab. 2014;46(5):26–8.
Sakamoto S, Putalun W, Vimolmangkang S, Phoolcharoen W, Shoyama Y, Tanaka H, et al. Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites. J Nat Med. 2018;72(1):32–42.
Junqueira LC, Carneiro J, Kelley R. Basic Histology. Lange Medical. Book; 1995.
Kawabata TT, Chapman MY, Dong-Hyun K, Stevens WD, Holsapple MP. Mechanisms of in vitro immunosuppression by hepatocyte-generated cyclophosphamide metabolites and 4-hydroperoxycyclophosphamide. Biochem Pharmacol. 1990;40(5):927–35.
Banerjee ER, Kar S, Konsam S, Hore G, Mitra S, Biswas S, et al. Therapeutic use of fisetin, curcumin, and mesoporous carbon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis. Biomed Res Ther. 2015;2(4):1–13.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
This work is licensed under a Creative Commons Attribution 4.0 International License.
