Abstract
The aim of this study was to assess the potential protective effect of zinc chloride (ZnCl2) as an antioxidant against the cytotoxic and mutagenic effects induced by yclophosphamide (chemotherapeutic agent), using mutagenicity tests; molecular assay, chromosomal aberrations (CA), and Mitotic index (MI) in vivo as the biomarkers. The experiment was designed as four groups (6 rats per group). Group 1 was injected intraperitoneally (i.p.) with saline solution (1 ml/kg body weight) every other day for 20 days and served as (control group). Group 2 (the treated group) was injected i.p. with a single dose of CP (200 mg/kg b. w.). Group 3 was injected i.p. with a single dose of CP (200 mg/kg b. w.) and treated simultaneous by ZnCl2 (4 mg/kg b. w.) every other day for 20 days, while group 4 (the protective group) was pretreated with ZnCl2 (4 mg/kg b. w.) every other day for 20 days, then treated with a single dose of CP (200 mg/kg b. w.) on the 21st day and was left. The experiment extended for 45 days after the treatment with the cyclophosphamide dose. The results revealed changes in the number, position, and intensity of DNA fragments for liver and kidney tissues in the treated rats with cyclophosphamide, in addition to significant decline in mitotic index and increase in the frequency of chromosomal aberrations compared with the control group. These results may be attributed to the fact that cyclophosphamide can induce genotoxicity through DNA damage in healthy cells. In comparison, rats that were treated simultaneous and pretreated with zinc chloride and then treated with a single dose of cyclophosphamide showed marked improvement in DNA fragments, decrease in the frequency of chromosomal aberration, and an elevation in mitotic index. Furthermore, pretreatment with zinc chloride revealed more protective role in mitotic index and reduce markedly DNA damage and chromosomal aberrations that induced by cyclophosphamide than those showed with the treatment with zinc chloride simultaneity with Cp treatment. Pretreatment of Zinc chloride may open an interesting field concerning its possible use in medicine applications, as a protective treatment to reduce the side effects that can occur by cyclophosphamide treatment and other chemotherapeutic agents.
Highlights
Cyclophosphamide (CP) is an effective anti-cancer alkylating agent, on the other hand it possesses cytotoxic effects towards normal cells (Kim et al., 2013)
The present study demonstrated that the treatment of rats with a single dose of cyclophosphamide caused DNA damage in liver and kidney tissues, as well as decline in mitotic index and increase in the frequency of the chromosomal aberrations in bon marrow cells, these results of the present study are in agreement with all pervious studies
The present data indicated that the pretreatment by zinc chloride or simultaneous treatment have good antimutangenic activity against cyclophosphamide induced genotoxicity, zinc being antioxidant or acting on DNA
Summary
Cyclophosphamide (CP) is an effective anti-cancer alkylating agent, on the other hand it possesses cytotoxic effects towards normal cells (Kim et al., 2013). Several previous studies reported that cyclophosphamide has carcinogenic effects in healthy human and animal tissues (Rehman et al, 2012), it causes gene mutations, chromosomal aberrations in mice tissues in vivo and in vitro test systems, and an elevated frequency of secondary treatment-related tumors in human cancer survivors (Ember et al, 1995;Ridder et al, 1998; Sundramoorthy et al, 2004; Kruawanand et al, 2006). Numerous studies using the Chromosome aberration (CA) and Mitotic index (MI) in vivo and in vitro as the biomarkers reported that treatment with cyclophosphamide can induce cytotoxic and mutagenic effects in bon marrow cells of rat and rabbit (Popov et al, 2011; Sharma et al, 2012; Sharma V. and Agrawal 2015; Sushma et al, 2015; Koura et al, 2017). Ii plays an important role in protecting DNA and other cellular components from oxidation and damage through its participating in vital processes such as transcription and replication of DNA through zinc finger proteins (Levine, 1997; Powell, 2000; Prasad, 2003; Ho, 2004; Emily, 2004; Ebisch et al, 2007; Leoni et al, 2014)
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