Sodium bicarbonate protects uranium-induced acute nephrotoxicity through uranium-decorporation by urinary alkalinization in rats.

To evaluate the effectiveness of sodium bicarbonate (SB) in removing uranium and protecting animals from uranium toxicity, we intramuscularly administered 1 mg/kg of uranyl nitrate to 8-wk-old male SD rats, and 20 min after administration of uranyl nitrate, the animals were given a single oral administration of SB at 0.1, 0.3 or 1 g/kg. The SB treatment at a dose of 0.3 g/kg or more raised the pH of the rats' urine until 4 h after treatment, and it significantly reduced the uranium amounts in the kidneys at 1 day after treatment. In another experiment, rats were intramuscularly administered 1 mg/kg of uranyl nitrate, and 20 min later, the animals were treated with sodium bicarbonate (0.1 or 1 g/kg). The rats were autopsied at 1, 3 and 7 days after uranium treatment. High-dose SB resulted in a significant increase in urinary uranium excretion in the first 24 h and a reduction of uranium deposition in the kidneys and femurs, and it also significantly suppressed uranium-induced renal toxicity, as shown by both histopathology and clinical chemistry at 3 days after uranium treatment. Low-dose SB did not show such marked effects. Our findings demonstrated that the uranium decorporation effect of sodium bicarbonate was observed at the dosage showing urine alkalinization in rats and that decorporation effect of sodium bicarbonate might be beneficial if it is administered immediately after incorporation of soluble uranium.

Acute toxicity of subcutaneously administered depleted uranium and the effects of CBMIDA in the simulated wounds of rats.

We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wound model (experiment I), and the effects of a chelating agent, catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA), on the removal and damages caused by uranium by local treatment for wounds in rats (experiment II). Experiment I: To examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg kg-1 DU in a solution of pH 1 and 7. The rats were killed 1, 3, 6, and 24 h after DU injection. The DU (pH 1) injection site on the skin was altered markedly by acid burn, and the chemical action of uranium compared with that of DU (pH 7). After the injection of 4 mg kg-1 DU (pH 1), about 60% of the uranium was retained 1-3 h at the injected sites and then decreased to 16% at 24 h. However, the concentration of uranium in the injected site after 16 mg kg-1 DU (pH 1) injection did not change significantly. Urinary excretion rates of uranium (pH 1) increased in a time-independent manner after the injection. Depositions of uranium in the liver, kidneys and femur were found at 1 h after DU injection, and the results of serum and urinary examinations indicated that severe damage in the organs, including the kidney, was induced. The results of the DU (pH 7) were useful for estimating the chemical toxicity of uranium. Experiment II: The effects of CBMIDA by local treatment for wounds with DU were examined. CBMIDA (480 mg kg-1) was infused into the DU-injected site 0, 10, 30, 60, 120 min, and 24 h after the subcutaneous injection of 4 mg kg-1 DU (pH 1 and 7). The uranium at the injected sites decreased to 4-17% of that at 24 h in the DU (pH 1) group without CBMIDA treatment in experiment I, when it was administered within 120 min after DU injection. In addition, CBMIDA had excellent efficacy in excreting the uranium in urine and feces and decreasing the concentrations of uranium in the kidneys and femur. However, there were no distinct effects of CBMIDA for DU (pH 7). In conclusion, the results indicated that the subcutaneous injected uranium acutely induced severe damage in the DU-injected sites and organs by chemical toxicity within a very short time after DU intake, despite the chemical forms of uranium used, and the local treatment of CBMIDA for wounds contaminated with DU was effective in decreasing the acute toxicity of uranium if carried out within 120 min after DU administration.

Comparative analysis of bacterial and archaeal communities in methanogenic sludge granules from upflow anaerobic sludge blanket reactors treating various food-processing, high-strength organic wastewaters.

A comprehensive survey of bacterial and archaeal community structures within granular sludges taken from twelve different types of full-scale, food-processing wastewater-treating, upflow anaerobic sludge blanket (UASB) reactors was performed with a 16S rRNA gene-based clone library method. In total, 1,282 bacterial 16S rRNA gene clones and 722 archaeal clones were analyzed, and their identities were determined by phylogenetic analyses. Overall, clones belonging to the bacterial phyla Proteobacteria (the class Deltaproteobacteria in particular), Firmicutes, Spirochaetes, and Bacteroidetes were observed in abundance within the bacterial clone libraries examined, indicating common bacterial denominators in such treatment systems. Within the domain Archaea, clones affiliated with the classes Methanomicrobia and Methanobacteria were found to be abundant in the archaeal libraries. In relation to features of reactor performance (such as chemical oxygen demand removal, fatty acid accumulation, and sludge bulking), possible representative phylotypes likely to be associated with process failures, such as sludge bulking and the accumulation of propionate, were found in comparative analyses of the distribution of phylotypes in the sludge libraries.

The effects of bicarbonate and its combination with chelating agents used for the removal of depleted uranium in rats.

The effects of bicarbonate and its combination with the chelating agents, deferiprone (L1), 4,6-dimethyl-1-hydroxypyrimidin-2(1H)-one (AK-4), catechol-3,6-bis(methyleneimino-diacetic-acid) (CBMIDA), and ethane-1-hydroxy-1,1-bisphoshonate (EHBP) in removing depleted uranium (DU) for radiation emergency medicine were examined. After the intramuscular injection of DU in rats, various time schedules of bicarbonate and chelating agent administration were tested. The results indicate that the bicarbonate helps increase significantly the effects of LI and AK-4, while there were no effects of using bicarbonate alone. The effects of bicarbonate on CBMIDA were unclear, and the effects of EHBP were negative. Further studies are necessary to obtain distinctly synergic effects by the combination of chelating agents with bicarbonate.

Effects of pH on du intake and removal by CBMIDA and EHBP.

The effects of pH on deleted uranium (DU) and DU removal by chelating agents, catechol-3,6-bis(methyleneiminodiacetic acid) (CBMIDA) and ethane-1-hydroxy-1,1-bisphoshonate (EHBP) in rats were examined. Ninety male Wistar rats, 8 wk old, were divided into six groups of 15 rats. Rats of five groups were each preinjected intraperitoneally with 8 mg kg(-1) DU in pH 1, 3, 5, 7, and 10 solutions. In each pH group, five rats were injected intraperitoneally with 240 mg kg(-1) CBMIDA, and the other five with 10 mg kg(-1) EHBP; the remaining five were used as the corresponding group with no chelating agent. One group was kept as the control (no injected DU) group, which consisted of five intact, five with CBMIDA, and five with EHBP administration. Chelating agents were administered for 3 d. Rats were injected with the DU 30 min prior to treatment with chelating agents on the first day. The gathered data indicated that the DU toxicity varied according to differences in pH; in addition, at pH 7, when varied DU-complexes formed, the DU toxicity including renal dysfunction increased, and the DU removal effects of chelating agents were not obtained. Both CBMIDA and EHBP were effective in excreting DU, reducing DU concentrations in organs, and preventing DU-induced toxicity, and CBMIDA was superior to EHBP, particularly in the prevention of renal dysfunction. These results indicate that the excretion and distribution of soluble DU changes and the removal effects of chelating agents according to pH differs, indicating that the treatment with chelating agent should begin in the DU-contaminated person as early as possible after an accident.

Radiation protection by deferiprone in animal models.

The effectiveness of deferiprone (L1) in removing depleted uranium (DU) and protecting animals from radiation exposure was examined. Rats that had received 2 mg/kg DU via intramuscular injection were orally administered 100, 200 or 400 mg/kg L1 for 3 days. In all of the groups, significant increases in urinary DU excretion and decreases in DU concentration in the injected muscle were observed, indicating that L1 combined with DU and DU was excreted in the urine. No significant increase in the amount of DU in the excreta or decrease in DU concentration in organs other than the muscles was found. As a preliminary test, the effectiveness of L1 in reducing radiation damage was examined in mice injected with 400 mg/kg L1 and rats administered orally with 200 and 400 mg/kg L1 before and just after x-ray exposure. The results were inconclusive.

Toxicity of uranium and the removal effects of CBMIDA and EHBP in simulated wounds of rats.

We examined the acute toxicity of uranium (99.3% 238U, 0.7% 235U) and the effects of Catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) and Ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on the removal of uranium after intramuscular injection as a simulated wound intake in rats. In this experiment, male Wistar rats, 8 wk old, were injected intramuscularly with uranyl nitrate in the femoral muscles. Experiment I: Rats died from 3 to 7 d after they were injected with five doses of 7.9, 15.8, 31.5, 63, and 126 mg kg(-1) uranium. The uranium retained 8.4-13.6% of the injected doses in the kidneys, showing the relationship between the injected dose and the retained concentration (r = 0.997). The excretion rates of the injected doses in the 63 and 126 mg kg(-1) uranium-injected rats were 1.73% and 3.09% in urine and 0.81% and 1.06% in feces on the first day, and 0.54% and 0.56% in feces on the second day, respectively. Experiment II: The retention of uranium at 1, 3, 6, and 24 h was examined after rats were injected with 63 mg kg(-1) uranium. The concentration of uranium decreased in the plasma, while it increased in the kidneys and femur until 6 h, and it continued to increase in the liver until 24 h. Experiment III: Rats were divided into four groups (n = 10) and were injected with a dose of 2 mg kg(-1) uranium. Two of the groups were then injected intraperitoneally with 240 or 480 mg kg-1 CBMIDA, and one group was injected with 10 mg kg(-1) EHBP once daily for 28 d, beginning 1 h after uranium injection on the first day. The fourth group was the non-treated control group. The survival rates at the end of the experiment were 80% and 40% in the 240 and 480 mg kg(-1) CBMIDA groups, 50% in the EHBP group, and 20% in the non-treated group. The successive administration of chelating agents was effective in decreasing the concentration of uranium in the kidneys, bone, and liver. The results indicated that uranium induces acute death and renal dysfunction by chemical toxicity, and both CBMIDA and EHBP were effective agents to prevent these effects.