Protective Effects of Zinc Chloride on Cyclophosphamide-Induced Genotoxicity in Male Albino Rat Tissues in vivo

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.