Abstract

Cyclophosphamide (CP) is a frequently used drug for its anticancer and immunosuppressive potential. However metabolism of CP in the body results into toxic chemical compounds (to the liver itself and other non-target vital organs) via oxidative stress, apoptosis induction and finally necrosis. Since there is no escaping of using such medications in spite of their harms this study was designed to access the ability to alleviate the side-effects of CP by using peach seed methanolic extract, due to its nutritional value and therapeutic properties. The peach seed extract has bioactive constituents such as phenols and carotenoids. Methanoloic extract is the most widely used since it offers a high recovery of antioxidant compounds. Mice were divided into five major groups: negative control (untreated group), positive control, was injected (IP) with CP in dose 75mg/kg b. wt., Third group received peach seed extract only in a dose of 500 mg/kg b.w., and the fourth and fifth groups received two doses of Peach seeds extract 500 and 250 mg/kg b.wt. after receiving a single dose of CP intraperitoneally. Assessment of the extract was performed using micronucleus test, mitotic chromosomal aberration assay using bone marrow cells, and liver samples were collected for histopathology. Our results demonstrated that CP induced highly significant e genotoxicity, which recorded 9.49% PE's with micronuclei, comparing to 1.03% as control, while the induction of chromosomal aberrations was recorded as 67.6% against 4.4% as negative control. The histological study on the liver cells recorded noticeable damage with liver cells treated with CP. After peach treatment a significant reduction in CP- induced damage was observed and those groups treated with both extract and CP became nearly similar to the untreated group in all tested parameters. peach methanolic seed extract has the potential to ameliorate the damaging effect of cyclophosphamide at both the genetic and histological levels.

Highlights

  • Chemotherapy is one of the most common approaches in cancer treatment, but it is associated with nearly lifethreatening side effects due to its indiscriminate action toward normal cells so it can be extremely difficult for cancer patients to endure [1]

  • We aimed to investigate the bioactivity of the peach Methanolic seed extract prepared by the traditional method to reduce and ameliorate the histological and cytogenetic alterations and DNA damages induced by CP

  • Our target in the present study is to explore the bioactivity of the peach methanolic seed extract on the cyclophosphamide- induced cytogenetic disorders and pathology of liver

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Summary

Introduction

Cyclophosphamide was developed by Brock and Hohorst [2]. It is used as immunosuppressant, chemotherapeutic and anti-cancer agent [3, 4]. It is the most widely used oxazaphosphorines and among the first alkylating agents to be used therapeutically, because phosphoramidase enzymes were thought to be more abundant in tumors compared with normal tissue [5]. Alkylating agents act by damaging DNA by forming guanine-guanine and guanine-adenine inter-strand crosslinks so they kill tumor cells by apoptosis [6, 7]

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