Hepatotoxicity and renal toxicity induced by gamma-radiation and the modulatory protective effect of Ficus carica in male albino rats.

It is well-known that gamma radiation initiates generation of free radicals which prompting serious cellular damages in biological systems. In the present study, we investigated the role of Ficus carica, a natural antioxidant substance, in modulating changes in liver and kidney functions, antioxidant enzyme's gene expression, and apoptosis, in male albino rats exposed to gamma radiation. A total of 40 rats were used in this experiment and divided equally into 4 groups: Group 1, rats administered distilled H2O (Control); Group 2, rats administered F. carica; Group 3, rats irradiated; and Group 4, rats treated with F. carica and irradiated. Groups 3 and 4 were exposed to whole-body gamma radiations at a dose level of 8 Gy and with a dose rate of 0.762 Gy/min. F. carica was administered to rats by gavage, for 3 consecutive weeks, before exposure to radiation. Five rats were sacrificed from each group at intervals of 24 and 72 h after cessation of treatment. The results revealed marked increases in alanine aminotransferase and aspartate aminotransferase levels in liver, a decrease in albumin level and increase in urea level in kidney. Irradiation resulted in cytotoxic effects as indicated by elevation in antioxidant enzyme's gene expression at 24 h, the opposite was observed at 72 h. Immunohistochemical analysis revealed that cytochrome c and p53 expressions significantly increased following exposure to radiation. Oral administration of F. carica pre-irradiation as a natural product plays a modulatory protective and anti-apoptotic role against cells damaged by free radicals induced by whole-body irradiation.

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.

Effect of microwave pretreatment on heterocyclic aromatic amine mutagens/carcinogens in fried beef patties.

To investigate a method to reduce the amount of mutagenic/carcinogenic heterocyclic aromatic amines formed during frying of ground beef, the mutagenic activity in Salmonella strain TA98 was assessed and the amount of known heterocyclic amines was determined by solid-phase extraction and HPLC. The beef patties received microwave treatment for various times before frying. Microwave pretreatment for 0, 1, 1.5, 2 or 3 min before frying at either 200 degrees C or 250 degrees C for 6 min per side reduced heterocyclic aromatic amine precursors (creatine, creatinine, amino acids, glucose), water, and fat up to 30%, in the patties and resulted in a decrease in mutagenic activity up to 95%. The sum of the four heterocyclic aromatic amines shown to be present--2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)--decreased three- to nine-fold compared with control, non-microwaved beef patties fried under identical conditions.

Modulation of NF-κB and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney.

The bioactive flavonoid baicalein has been shown to have radioprotective activity, although the molecular mechanism is poorly understood in vivo. C57BL/6 mice were irradiated with X-rays (15 Gy) with and without baicalein treatment (5 mg/kg/day). Irradiation groups showed an increase of NF-κB-mediated inflammatory factors with oxidative damage and showed inactivation of FOXO and its target genes, catalase and SOD. However, baicalein suppressed radiation-induced inflammatory response by negatively regulating NF-κB and up-regulating FOXO activation and catalase and SOD activities. Furthermore, baicalein inhibited radiation-induced phosphorylation of MAPKs and Akt, which are the upstream kinases of NF-κB and FOXOs. Based on these findings, it is concluded that baicalein has a radioprotective effect against NF-κB-mediated inflammatory response through MAPKs and the Akt pathway, which is accompanied by the protective effects on FOXO and its target genes, catalase and SOD. Thus, these findings provide new insights into the molecular mechanism underlying the radioprotective role of baicalein in mice.

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.