Modulation of radiation-induced organs toxicity by cremophor-el in experimental animals.

Pharmacological and cytogenetic evaluations of the protective effects of polyethoxylated castor oil cremophor-EL (cremophor) against hepato, renal and bone marrow toxicity induced by gamma irradiation in normal rats were carried out. A single dose of irradiation (6 Gy) caused hepatic and renal damage manifested biochemically as an elevation in levels of serum alanine and aspartate aminotransferase as well as an increase in blood urea. Cremophor administration at a dose level of 50 microl kg-1 intravenously 1 day before exposure to irradiation (6 Gy) protected the liver and kidney as indicated by the recovery of levels of hepatic aminotransferase, urea and lipid profiles to normal values. Gamma irradiation of male rats caused a decrease in reduced glutathione and an increase in the oxidized form in rat-liver homogenate. A highly significant increase in the incidence of micronucleated normochromatic erythrocytes and micronucleated polychromatic erythrocytes was observed after irradiation exposure. The induced genotoxicity in the bone marrow cells was corrected by pretreatment with cremophor. The findings of this study suggest that cremophor pretreatment can potentially be used clinically to prevent irradiation-induced hepato, renal and bone marrow toxicity without interference with its cytotoxic activity.

The modifying effect of beta-carotene on gamma radiation-induced elevation of oxidative reactions and genotoxicity in male rats.

The aim of the present work was to evaluate the modulatory role of beta-carotene on the radiation-induced changes in certain biochemical and cytogenetic parameters. beta-Carotene was given by gavage at a dose of 5 mg/kg body weight for 7 consecutive days before whole body gamma irradiation with 7 Gy (single dose). The levels of beta-carotene in plasma, thiobarbituric acid-reactive substances (TBARS) in plasma and liver, the activities of superoxide dismutase (SOD) and catalase in blood and liver were the selected parameters. Furthermore, the frequency of micronuclei (MN) of polychromatic erythrocytes (PCEs), normochromatic erythrocytes (NCEs), the ratio of PCEs/NCEs and the mitotic index (MI) of bone marrow cells were also evaluated. The biochemical and cytogenetic determinations were carried out 1, 24, and 72 h after radiation exposure. The results obtained revealed that administration of beta-carotene pre-irradiation significantly inhibited the decrease in plasma beta-carotene, significantly reduced the levels of TBARS in plasma and liver. Significant protection of the radiation-induced changes in the activities of SOD and catalase was also recorded in the blood and liver of beta-carotene-treated and -irradiated rats. beta-Carotene resulted in significant inhibition in the frequency of radiation-induced MN, as well as in the ratio of PCEs/NCEs and the MI of bone marrow cells. These results suggest that beta-carotene as a natural product with its antioxidant capacity and capability of quenching singlet oxygen, could play a modulatory role against the cellular damage affected by free radicals induced by whole body irradiation.

Radioprotective effect of melatonin assessed by measuring chromosomal damage in mitotic and meiotic cells.

This study was taken to evaluate the radioprotective effects of melatonin. Male adult albino mice were treated (intraperitoneal, i.p.) with 10 mg/kg melatonin either 1 h before or 1/2 h after exposure to 1.5 Gy of gamma-irradiation. Control, melatonin, irradiated and melatonin plus irradiation groups were sacrificed 24 h following treatment. The incidence of micronuclei (MN) in bone marrow cells was determined in all groups. The results show that melatonin caused a significant reduction in micronuclei polychromatic erythrocytes (MNPCE) when animals were treated with melatonin before and not after exposure to radiation. Mitotic and meiotic metaphases were prepared from spermatogonial and primary spermatocytes, respectively. Examination and analysis of metaphases showed no mutagenic effect of melatonin on chromosomal aberration (CA) frequency in spermatogonial chromosomes. Administration of one single dose of melatonin to animals before irradiation lowered total CA from 46 to 32%. However, no significant effect was observed when melatonin was given after irradiation. Similarly, the frequency of CA in meiotic metaphases decreased from 43.5% in the irradiated group to 31.5% in the irradiated group treated with melatonin 1 h before irradiation, but no change was observed when melatonin was administered after irradiation. The data obtained in this study suggest that melatonin administration confers protection against damage inflicted by radiation when given prior to exposure to irradiation and not after, and support the contention that melatonin radioprotection is achieved by its ability as a scavenger for free radicals generated by ionizing radiation.

The mutagenic versus protective role of vitamin A on the induction of chromosomal aberration in human lymphocyte cultures.

The present study was carried out to evaluate the role of vitamin A (VA) on the induction of chromosomal aberrations (CA) in lymphocyte culture system and to investigate its modulating effect on chromosomal damage induced by gamma irradiation. Lymphocyte cultures from five healthy normal adult males were either treated with VA at a dose level of 2.0, 8.0 or 24.0 microg/ml or exposed to gamma-irradiation of 3.0 Gy, then followed immediately by a treatment with one of the above mentioned doses of VA. Non-treated cultures and cultures exposed to gamma-irradiation served as control for the two sets of experiments. Cultures were set up in duplicates and incubated for 48 h for assessment of CA. Treatment with VA alone increased CA demonstrating a dose-response effect. Addition of VA to gamma-irradiated cultures resulted in an inverse protective effect as the low dose of 2 microg/ml reduced the CA induced by radiation to about 1/3 rd whereas a dose of 8 microg/ml had a protective effect of 40% of the total damage and the large dose of 24 microg/ml had no or little effect. These results suggest that a proportion of the added VA may interfere with the radiation induced free radicals and other reactive metabolites which elevate CA. On the other hand, excessive amounts of VA increased toxicity and reduced effect on repair enzymes.