Genotoxicity and sperm defects induced by 5-FU in male mice and the possible protective role of Pentas lanceolata-iridoids
| Autor: | Zeinab M. Hassan, Heba-tollah M. Sweelam, Howaida I. Abd-Alla, Maha A. Fahmy, Entesar E. S. Hassan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Infertility Health Toxicology and Mutagenesis Rubiaceae 010501 environmental sciences Biology medicine.disease_cause 01 natural sciences Andrology Mice 03 medical and health sciences Spermatocytes Genetics medicine Animals Cytotoxic T cell Iridoids 0105 earth and related environmental sciences Chromosome Aberrations Pentas lanceolata Mutagenicity Tests Plant Extracts medicine.disease biology.organism_classification Spermatozoa Sperm 030104 developmental biology medicine.anatomical_structure Fluorouracil Bone marrow Reproductive toxicity Micronucleus Genotoxicity DNA Damage |
| Zdroj: | Mutation Research/Genetic Toxicology and Environmental Mutagenesis. :503145 |
| ISSN: | 1383-5718 |
| DOI: | 10.1016/j.mrgentox.2020.503145 |
| Popis: | 5-Fluorouracil (5-FU) is a widely used antineoplastic drug. In this work, a comprehensive study was performed to detect the extent of chromosomal damage and morphological sperm defects induced by 5-FU in male mice and the possible protective role of the iridoids-rich fraction of Pentas lanceolata leaves (IFPL). Six main groups were examined in micronucleus and chromosomal assays: I- control negative, II- control positive (i.p. treated with single dose of 75 mg/kg 5-FU), III- control plant (orally administrated IFPL, 300 mg/kg, 5 consecutive days), and IV-VI- treated with IFPL (100, 200 and 300 mg/kg, 5 consecutive days) plus 5-FU (i.p. treated at the last day). Samples were taken 24 h post treatment. The study of morphological sperm anomalies, single and repeated treatments were examined and samples were taken after 35 days from the 1st treatment. In bone marrow, 5-FU induced a significant increase in the micro-nucleated polychromatic erythrocytes, chromosome anomalies (CAs) and also cytotoxic effects. A significant percentage of CAs was recorded in spermatocytes after 5-FU treatment reached 22.80 ± 1.32 vs 4.20 ± 0.37 for control (mainly X-Y univalent, 90%). IFPL was recorded to be non-mutagenic in all tests examined. In addition, it alleviated the previous defects in a dose-dependent manner. A significant and dramatic increase in the percentage of morphological sperm defects was recorded after single and repeated treatments with 5-FU reached 13.24 ± 0.24, 30.42 ± 0.32 respectively vs 2.56 ± 0.14 for control. Amorphous head-sperm and sperm with coiled tail were the most pronounced types of abnormalities. Significant protection was detected with the highest tested dose of IFPL. In conclusion: 5-FU demonstrated to be a genotoxic agent. Its genotoxicity in germ cells is serious and may lead to reproductive toxicity, infertility or heritable defects. The results also demonstrated the biosafety of IFPL and its possible protective role in combined treatment with 5-FU. |
| Databáze: | OpenAIRE |
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