Administration Of Potassium Bromate Research Articles

Quercetin flavonoid and vitamin C recuperate kidney functions in potassium bromate-induced renal dysfunction in Wistar rats.

Studies into the functions and mechanisms of action of quercetin may be able to help dispel the negative effects of toxicants on renal toxicity due to its anti-inflammatory potential, as well as provide a simple, low-cost alternative for treating renal toxicity in developing nations. Therefore, the present study evaluated the ameliorative and renal protective activities of quercetin dihydrate in potassium bromate-induced, renal-toxic Wistar rats. Forty-five (45) mature female Wistar rats (180-200 g) were randomly grouped into nine (9) (n = 5). Group A served as general control. Nephrotoxicity was induced in groups B to I with the administration of potassium bromate. While group B served as a negative control, groups C-E received graded doses of quercetin (40, 60, and 80 mg/kg, respectively). Group F received 2.5 mg/kg/day of vitamin C, while groups G-I received vitamin C (2.5 mg/kg/day) and co-administration of a graded dose of quercetin (40, 60, and 80 mg/kg, respectively). Daily urine levels and final blood samples by retro-orbital techniques were collected for GFR, urea, and creatinine level assessment. The collected data were subjected to ANOVA and Tukey's post hoc test, and the results were presented as mean SEM with a p < 0.05 level considered significant. Body and organ weight and GFR were significantly reduced (p < 0.05), while serum and urine creatinine and urea were decreased in renotoxic animals. However, treatment with QCT reversed the renotoxic effects. We, therefore, concluded that quercetin administered alone or with vitamin C conferred renal protection by reversing KBrO3-induced renal toxicity in rats. Further studies to corroborate the present findings are recommended.

Study of Histological Changes in the Liver and Kidneys of Albino Mice Caused by Administration of Potassium Bromate

Study of Histological Changes in the Liver and Kidneys of Albino Mice Caused by Administration of Potassium Bromate

Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice

BackgroundBase pair mismatches in genomic DNA can result in mutagenesis, and consequently in tumorigenesis. To investigate how mismatch repair deficiency increases mutagenicity under oxidative stress, we examined the type and frequency of mutations arising in the mucosa of the small intestine of mice carrying a reporter gene encoding guanine phosphoribosyltransferase (gpt) and in which the Msh2 gene, which encodes a component of the mismatch repair system, was either intact (Msh2+/+::gpt/0; Msh2-bearing) or homozygously knockout (KO) (Msh2−/−::gpt/0; Msh2-KO).ResultsGpt mutant frequency in the small intestine of Msh2-KO mice was about 10 times that in Msh2-bearing mice. Mutant frequency in the Msh2-KO mice was not further enhanced by administration of potassium bromate, an oxidative stress inducer, in the drinking water at a dose of 1.5 g/L for 28 days. Mutation analysis showed that the characteristic mutation in the small intestine of the Msh2-KO mice was G-to-A transition, irrespective of whether potassium bromate was administered. Furthermore, administration of potassium bromate induced mutations at specific sites in gpt in the Msh2-KO mice: G-to-A transition was frequently induced at two known sites of spontaneous mutation (nucleotides 110 and 115, CpG sites) and at nucleotides 92 and 113 (3′-side of 5′-GpG-3′), and these sites were confirmed to be mutation hotspots in potassium bromate-administered Msh2-KO mice. Administration of potassium bromate also induced characteristic mutations, mainly single-base deletion and insertion of an adenine residue, in sequences of three to five adenine nucleotides (A-runs) in Msh2-KO mice, and elevated the overall proportion of single-base deletions plus insertions in Msh2-KO mice.ConclusionsOur previous study revealed that administration of potassium bromate enhanced tumorigenesis in the small intestine of Msh2-KO mice and induced G-to-A transition in the Ctnnb1 gene. Based on our present and previous observations, we propose that oxidative stress under conditions of mismatch repair deficiency accelerates the induction of single-adenine deletions at specific sites in oncogenes, which enhances tumorigenesis in a synergistic manner with G-to-A transition in other oncogenes (e.g., Ctnnb1).

Potassium bromate – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)

Potassium bromate (V), (KBrO3) exists as white crystals, crystalline powder or granules. It is highly soluble in water, tasteless and odourless. Potassium bromate is a strong oxidizing agent. In the past it has been used as food additive in flour milling, as an ingredient in fish-paste in Japan, in cheese making, in beer malting, as a component of cold hair wave liquid and an oxidizing compound. Moreover, bromate is formed as a by-product of water disinfection by ozonation and is frequently detected in tap and bottled water. In fact bromate is one of the most prevalent disinfection by-product of surface water. Occupational exposure to potassium bromate occurs mainly in production plants during packaging processes. In Poland, about 1 160 persons were exposed to this compound in 2016. Bromate caused many acute poisonings by accidental ingestion, mainly among children, and more often ingested for tentative suicide by young women, especially hairdressers. In the acute phase of poisoning, gastrointestinal disturbances, irreversible hearing loss, and acute renal failure were observed. Acute renal failure was associated with hemolytic uremic syndrome. There are no data on chronic intoxication of humans by potassium bromate and epidemiological studies on this subject. On the basis of the value of median lethal dose (LD50) per os in rat, potassium bromate has been classified as a compound belonging to the category „Toxic”. Major toxic signs and symptoms in animals after a single intragastric administration of potassium bromate were tachypnea, hypothermia, diarrhea, lacrimation, suppression of locomotor movement, ataxic gait, and animals lying in a prone position. At autopsy the major findings were strong hyperemia of glandular stomach mucosa and congestion of lungs. Microscopically, necrosis and degenerative changes of the proximal tubular epithelium and hearing cells of internal ear were found. It was stated that the compound is not irritating, corrosive or sensitizing. In subchronic and chronic exposure of rodents, potassium bromate led to liver and kidney dysfunction and tubular epithelial damage. Potassium bromate had mutagenic and clastogenic effects. It induced point mutations, structural chromosome aberrations, micronuclei in polychromatic erythrocytes in male mice, DNA oxidative damage by modification of deoxyguanosine to 8-hydroxydeoxyguanosine, and DNA double-strand breakage. Potassium bromate induced neoplasms in rodents and exerted promotion effect in comparison with well-known carcinogens. Besides from preneoplastic changes, expressed by high incidences of renal cell tumors and dysplastic foci, bromate induced solid neoplasms, such as adenomas and adenocarcinomas in a rat kidney and thyroid, and mesotheliomas of peritoneum and tunica vaginalis testis. The European Union classified potassium bromate as a substance that can cause cancer (Group 1.B), whereas IARC classified it as a presumably carcinogenic agent for human (Group 2.B). In principle, effects of bromate on reproduction and ontogenetic development of offspring were not observed. Animal studies suggest that a kidney is a critical organ in the exposure to potassium bromate. The results of subchronic exposure of male rats to potassium bromate administered with drinking water were used to calculate the value of MAC-NDS. The critical effects in kidney were: an increase of organ weight and dose-dependent histopathological alterations defined as epithelium urinary tract hypertrophy. The NOAEL value is 1.5 mg/kg b.w./day. For the calculation of the maximum allowable concentration (MAC) value, 5 uncertainty factors with total value of 24 were used. Based on this estimation it is proposed to accept the MAC-TWA value for potassium bromate at 0.44 mg/m3. The risks of kidney and thyroid cancer in condition of occupational exposure are 2.2 · 10-3 and 0.6 · 10-3, respectively. There is no reason to determine the value of short-term exposure limit (STEL) and the biological exposure index (BEI). „Carc.1.B” notation (carcinogenic substance) was proposed

The Effectiveness of Bandotan Herb (Ageratum Conyzoides L.) as Blood Uric Acid Levels Reduction in Mencit with Allopurinol Comparison

Traditionally herb bandotan (Ageratum conyzoides L.) are used for various treatments among them for stiff healing, eliminate swelling, and pain. The pain and sciatica is likely to be due to the high levels of uric acid in the blood, then to scientifically proves the presence of a relationship of aches and pains with a decrease in uric acid in the blood necessary to test the effectiveness of herbal extracts bandotan to decrease blood uric acid levels male mice. Extraction is done by percolation using 80% ethanol. The study begins with phytochemical screening test performed on fresh herbs, botanicals and herbal extracts bandotan ethanol. Decreased levels of uric acid is measured by using a measuring device Easy Touch uric acid levels in the blood of male mice hyperuricemia induced by administration of potassium bromate 0.5 mg / kg. The data obtained were analyzed by analysis of variance (ANAVA) followed by analysis of Least Significant Difference Test (LSDT) using the least squares difference with a 99% confidence level. Phytochemical screening result looks the same class of chemical compounds in fresh herbs, botanicals and herbal extracts ethanol bandotan, namely alkaloids, flavonoids, tannins, triterpenoids / steroids; and essential oils. The result of the effect of decreasing uric acid levels showed there has been a reduction in the dose of 50 mg / kg, but is still too small, and according to the results of statistical test Analysis of Varian (ANOVA) and test Least Significant Difference Test (LSDT) dose of 100 mg / kg body weight have an effect reduction in uric acid levels were not significantly different with allopurinol dose of 10 mg / kg.

Renal biomarker changes associated with hyaline droplet nephropathy in rats are time and potentially compound dependent

Alpha 2u-globulin mediated hyaline droplet nephropathy (HDN) is a male rat specific lesion induced when a compound or metabolite binds to alpha 2u-globulin. The objective of this study was to investigate if the newer and more sensitive renal biomarkers would be altered with HDN as well as be able to distinguish between HDN and oxidative stress-induced kidney injury. Rats were dosed orally for 7 days to determine (1) if HDN (induced by 2-propanol or d-limonene) altered the newer renal biomarkers and not BUN or creatinine, (2) if renal biomarkers could distinguish between HDN and oxidative stress-induced kidney injury (induced by potassium bromate), (3) sensitivity of HDN-induced renal biomarker changes relative to d-limonene dose, and (4) reversibility of HDN and renal biomarkers, using vehicle or 300mg/kg/day d-limonene with 7 days of dosing and necropsies scheduled over the period of Days 8–85. HDN-induced renal biomarker changes in male rats were potentially compound specific: (1) 2-propanol induced mild HDN without increased renal biomarkers, (2) potassium bromate induced moderate HDN with increased clusterin, and (3) d-limonene induced marked HDN with increased αGST, μGST and albumin. Administration of potassium bromate did not result in oxidative stress-induced kidney injury, based on histopathology and renal biomarkers creatinine and BUN. The compound d-limonene induced a dose dependent increase in HDN severity and renal biomarker changes without altering BUN, creatinine or NAG: (1) minimal induction of HDN and no altered biomarkers at 10mg/kg/day, (2) mild induction of HDN with increased αGST and μGST at 50mg/kg/day and (3) marked induction of HDN with increased αGST, μGST and albumin at 300mg/kg/day. HDN induced by d-limonene was reversible, but with a variable renal biomarker pattern over time: Day 8 there was increased αGST, μGST and albumin; on Day 15 increased clusterin, albumin and Kim-1. In summary, HDN altered the newer and more sensitive renal biomarkers in a time and possibly compound dependent manner.

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.

Comparative Studies on Lipid Peroxidation in the Kidney of Rats, Mice, and Hamsters and on the Effect of Cysteine, Glutathione, and Diethyl Maleate Treatment on Mortality and Nephrotoxicity After Administration of Potassium Bromate

As an index of lipid peroxidation (LPO), levels of thiobarbituric acid (TBA)-reactive substances were examined in the kidneys of male F344 rats, BDF1, CDF1, and B6C3F1 mice, and Syrian golden hamsters after a single intravenous (IV) administration of potassium bromate (KBrO3) at various doses. In the rats, LPO levels were significantly increased in both a dose-dependent and time-dependent manner. However, when the rats were given intraperitoneal (IP) injection of cysteine, the levels of LPO were not significantly different between KBrO3-treated animals and controls. In CDF1 mice, the slight increases in LPO levels observed were much weaker and not statistically significant. On the other hand, treatment of BDF1 and B6C3F1 mice or hamsters with KBrO3 resulted in decreased values as compared to controls. The effect of treatment with cysteine, glutathione (GSH), or diethyl maleate (DEM) on mortality was tested in male F344 rats given IV injection of KBrO3 at various doses. Significant reduction and elevation in the mortality were observed in rats treated with cysteine or GSH and DEM, respectively. Significant dose-dependent and time-dependent increases were observed in the levels of serum non-protein nitrogen (NPN), blood urea nitrogen (BUN), and creatinine, and absolute and relative weight of the kidneys in male F344 rats administered KBrO3 IV. Microscopically, the appearance of numerous eosinophilic droplets in the cytoplasm of proximal tubular epithelium of KBrO3-treated rats was noteworthy. All these changes were reduced and exacerbated by treatment with cysteine or GSH and DEM, respectively. The possibility of LPO formation in the kidney by active oxygen radicals generated by KBrO3 is suggested. A possible relationship between LPO levels in the kidney and species differences in the renal toxicity and carcinogenicity of KBrO3 is implicated.