Molecular and cytogenetic evaluation for potential genotoxicity of hydrocortisone

Abstract

Objective: To assess the risk of hydrocortisone sodium succinate through different end points of genotoxicity. Methods: The study examined the induction of chromosomal aberrations in bone marrow cells, morphological sperm abnormalities, the effect on dominant lethal gene and protein synthesis. Hydrocortisone was given intraperitoneally at three dose levels 26, 39 and 52 mg/kg body weight which was equivalent to the therapeutic doses in man. Results: The results showed that single dose treatment with different doses had no effect on chromosomal aberrations. The dose of 52 mg/kg body weight induced significant percentage of chromosomal aberrations in bone marrow cells after repeated treatment for 7 and 14 days. Significant effect of morphological sperm abnormalities was demonstrated only after treatment with the dose of 52 mg/kg body weight. For examining the dominant lethal mutation, male mice were injected with dose of 39 mg/kg body weight for 5 consecutive days. Mating between treated males and virgin untreated females were performed at different time intervals. The results showed that the percentage of fertile mating at 1-7 and 8-14 days reduced to 50% and 60% respectively compared with control group while no effect was recorded at 15-21 days. The percentage of dominant lethal mutation reached 0.32%, 4.4% and 0% in mating intervals respectively indicating pronounced effect of hydrocortisone at the interval 8-14 days which represented by the late spermatids. The results also showed that the repeated treatment with the dose of 52 mg/kg body weight inhibited protein synthesis which contributed to the cytotoxic effect of the drug. Conclusions: It is concluded that long term treatment with large doses of hydrocortisone may have genotoxic effect.