Molecular and cytogenetic evaluation for potential genotoxicity of hydrocortisone

Objective: To assess the risk of hydrocortisone sodium succinate through different end points\udof genotoxicity.\udMethods: The study examined the induction of chromosomal aberrations in bone marrow cells,\udmorphological sperm abnormalities, the effect on dominant lethal gene and protein synthesis.\udHydrocortisone was given intraperitoneally at three dose levels 26, 39 and 52 mg/kg body\udweight which was equivalent to the therapeutic doses in man.\udResults: The results showed that single dose treatment with different doses had no effect on\udchromosomal aberrations. The dose of 52 mg/kg body weight induced significant percentage\udof chromosomal aberrations in bone marrow cells after repeated treatment for 7 and 14 days.\udSignificant effect of morphological sperm abnormalities was demonstrated only after treatment\udwith the dose of 52 mg/kg body weight. For examining the dominant lethal mutation, male\udmice were injected with dose of 39 mg/kg body weight for 5 consecutive days. Mating between\udtreated males and virgin untreated females were performed at different time intervals. The\udresults showed that the percentage of fertile mating at 1–7 and 8–14 days reduced to 50% and\ud60% respectively compared with control group while no effect was recorded at 15–21 days.\udThe percentage of dominant lethal mutation reached 0.32%, 4.4% and 0% in mating intervals\udrespectively indicating pronounced effect of hydrocortisone at the interval 8–14 days which\udrepresented by the late spermatids. The results also showed that the repeated treatment with the\uddose of 52 mg/kg body weight inhibited protein synthesis which contributed to the cytotoxic\udeffect of the drug.\udConclusions: It is concluded that long term treatment with large doses of hydrocortisone may\udhave genotoxic effect