KBrO3 Administration Research Articles

Toxicological Study of Potassium Bromate. III. Effects of Vitamin E on the Potassium Bromate Administered to Rats.

The antioxidative effects of vitamin E (VE) on the administration of potassium bromate (KBrO3) were examined. Five-week-old SPF-SD male rats were fed the VE enriched diets containing 250 or 1000 ppm VE in commercial diet (CE-2, VE 70ppm) for 4 weeks. KBrO3 was given in drinking water for 4 weeks at the concentration of 1000 μg/ml and the following results were obtained. 1. KBrO3 administration inhibited the gain in body weight, while it increased the weight of kidney in rats. 2. The contents of urea nitrogen (UN) and creatinine in the serum increased remarkably and the kidney injury was observed in the groups with KBrO3 administration. 3. The activities of alkaline phosphatase (EC 3.1.3.1, ALP) and γ-glutamyl transpeptidase (EC 2.3.2.2, γ-GTP) in the kidney cytosols decreased to be about 60-70% of those in control groups. 4. The thiobarbituric acid reactive substances (TBRAS) contents in the liver and kidney homogenates decreased in the groups with VE enriched diet administration.

The protective role of glutathione, cysteine and vitamin C against oxidative DNA damage induced in rat kidney by potassium bromate.

The roles of glutathione (GSH), cysteine, vitamin C., liposome‐encapsulated superoxide dismutase (L‐SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO3) to male F344 rats were investigated by measuring 8‐hydroxydeoxyguanosine (8‐OH‐dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre‐ and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8‐OH‐dG, LPO levels and RKW caused by 80 mg/kg KBrO3 i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8‐OH‐dG, LPO levels and RKW after a 20 mg/kg KBrO3 i.p. treatment, which itself caused no change. Administration of KBrO3 itself reduced renal non‐protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO3 lowered the non‐protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO3 were also observed for pre‐ and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre‐ and posttreatment with 18,000 U/kg L‐SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO3.

Toxicological Study of Potassium Bromate. II. Hepatotoxic Effects of the Potassium Bromate and Benzo(a)pyrene Simultaneous Administration in Mice.

The short-term in vivo expression of precarcinogenicity of potassium bromate (KBrO3), a food additive, was examined. KBrO3 was orally administered singly or in combination with benzo-[a] pyrene (B [a] P) or B [a] P alone, in male of 6 week-old SPF-ddy mice. KBrO3 was given in the drinking water for two weeks at concentration of 5000, 2500, 1000, 500 or 100 ppm. KBrO3-B [a] P simultaneous administration groups were given in the corn oil solution of B [a] P at 100 mg/kg, once a week for two weeks. The results obtained were as follows : 1. The body weight gains were inhibited by KBrO3 of a high concentration (5000 ppm). But, after the administration the organ weights of the liver, lung and kidney showed no difference among groups administered with KBrO3. 2. As for tumor makers, α-fetoprotein (AFP), alkaline phosphatase (EC 3.1.3.1, ALP) and γ-glutamyl transpeptidase (EC 2.3.2.2, γ-GTP) activities in the plasma were determined. The results of this experiment demonstrated that the AFP values increased in KBrO3 groups and KBrO3-B [a] P simultaneous groups, 2-3 fold that of the control group given distilled water alone. AFP value and ALP activitiy increased independently of the dosage of KBrO3. Moreover, the γ-GTP activities more significantly increased in all experimental groups than that of the control, and also showed the same results additively by simultaneous administration of KBrO3 and B [a] P. However, the γ-GTP activities in the liver were not remarkably enhanced in all experimental groups. These results suggested that formation of oxygen radicals in the target organs such as the liver, kidney and lung was closely related to KBrO3 precarcinogenesis.

Relationship between the duration of treatment and the incidence of renal cell tumors in male F344 rats administered potassium bromate.

In order to ascertain the minimum induction time, minimum treatment period and total dose required for development of renal cell tumors, KBrO3 at a concentration of 500 ppm was administered in the drinking water to a total of 232 male F344 rats divided into 14 experimental groups and the development of tumors was examined by two different approaches. In a continued-treatment study, administration of KBrO3 was stopped at week 13, 26, 39, 52 or 104 and rats were immediately sacrificed for comparison with controls given distilled water (DW) alone. Renal cell adenomas were found as early as after 26 weeks of treatment with KBrO3. The yields of dysplastic foci, adenomas and adenocarcinomas of the kidney, follicular cell tumors of the thyroid and mesotheliomas of the peritoneum increased with treatment, the final incidences all being statistically significant after administration of KBrO3 for 104 weeks. To examine the effect of discontinued treatment, on the other hand, the rats were given KBrO3 for the first 13, 26, 39 or 52 weeks and were subsequently maintained on DW alone until sacrifice at week 104. The incidences of tumors in these groups were compared with that of a group continuously administered KBrO3 for 104 weeks. The yields of renal dysplastic foci, adenomas and adenocarcinomas in all discontinued-treatment groups were approximately equal to or even higher than those in the group given KBrO3 continuously for 104 weeks. It is concluded that, under the conditions of this study: the minimum induction time for the development of renal adenomas was 26 weeks and the minimum treatment period and total dose for the induction of renal adenomas and adenocarcinomas were 13 weeks and 4 g/kg, respectively, when the rats were maintained thereafter on DW for 2 years.