Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice

Abstract Carmustine (Cr) is an important chemotherapeutic drug widely used in the treatment of brain tumors. Herein, the genotoxic side effect of Cr was evaluated by using different cytogenetic parameters. Also, the protective role of Codiaeum variegatum leaves ethyl acetate fraction at different doses was determined. The technique HPLC-qTOF-MS/MS was used to identify the constituents in C. variegatum. A total of 90 male mice was used to evaluate micronuclei (MPCEs) in bone marrow, chromosomal aberration (CAs) in the bone marrow and mouse spermatocytes, sperm abnormalities, and gene expression (qRT-PCR). The following groups were included, I: Control negative (ethanol 30%), II: Control positive (i.p injected once with 30 mg/kg Cr), III: Control plant orally treated with C. variegatum at 500 mg/kg, four days). IV-VI: treated with 100, 300, and 500 mg/kg of the plant (4 days) plus a single dose of Cr on the last day of treatment. The results revealed the genotoxic effect of Cr in somatic cells evidenced by increasing in MPCEs and CAs by 3 and 7- folds respectively over the corresponding control. Cr also induced a significant percentage of CAs in spermatocytes in meiosis in the form of univalent (X-Y and autosomal univalent) and also a significant percentage of morphological sperm abnormalities was recorded. A large number of coiled tail abnormalities were detected indicating the effect of Cr in sperm motility. Cr also induced an overexpression of the P53 gene. C. variegatum mitigated all deleterious genotoxic effects of Cr with a dose-related relationship. By using HPLC-qTOF-MS/MS analysis, it was found that flavones (35.21%), phenolic acids (17.62%), flavonols (3.40%), isoflavones (0.53%), constitute mainly the polyphenolic components of the leaves. Other important phytochemicals (8.29–0.49%) such as coumarins, indoles, fatty acids, and amino acids, were also identified. Such components together participate in the obtained protective role of C. variegatum.