potassium-bromate and Kidney-Diseases

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

Topics: Adenocarcinoma; Administration, Oral; Animals; Bread; Bromates; Bromides; Carcinogenicity Tests; Carcinogens; Carcinoma, Renal Cell; Chromosome Aberrations; Cocarcinogenesis; Cricetinae; Cysteine; Dose-Response Relationship, Drug; Fish Products; Food Additives; Food Handling; Glutathione; Hair Preparations; Hearing Loss; Humans; Japan; Kidney Diseases; Kidney Neoplasms; Maximum Allowable Concentration; Mesocricetus; Mesothelioma; Mice; Mutagenicity Tests; Occupational Diseases; Peritoneal Neoplasms; Potassium; Potassium Compounds; Rats; Rats, Inbred F344; Species Specificity; Thyroid Neoplasms; United Kingdom; United States

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 KBrO

Topics: Animals; Antioxidants; Ascorbic Acid; Creatinine; Female; Flavonoids; Kidney; Kidney Diseases; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Renal Insufficiency; Urea

Potassium bromate (KBrO

Topics: Animals; Bromates; DNA Damage; Humans; Kidney; Kidney Diseases; Lipid Peroxidation; Lycium; Male; Oxidative Stress; Plant Extracts; Polysaccharides; Rats; Rats, Wistar

Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. Several studies have shown that it causes nephrotoxicity in humans and experimental animals. We have investigated the potential role of the sulfonic amino acid taurine in protecting the kidney from KBrO3-induced damage in rats. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine + KBrO3. Administration of single oral dose of KBrO3 alone caused nephrotoxicity as evident by elevated serum creatinine and urea levels. Renal lipid peroxidation and protein carbonyls were increased while total sulfhydryl groups and reduced glutathione levels were decreased suggesting the induction of oxidative stress. The enzymes of renal brush border membrane were inhibited and those of carbohydrate metabolism were altered. There was an increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive renal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine + KBrO3 group. These results show that taurine is an effective chemoprotectant against bromate-induced renal damage and this amino acid could prove to be useful in attenuating the toxicity of this compound.

Topics: Animals; Bromates; DNA Damage; Humans; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar; Taurine

Male F344 rats were exposed to potassium bromate (KBrO₃) in drinking water at concentrations of 0, 5, 20, 100, 200, or 400 mg/L for 2 or 13 weeks. Endpoints evaluated included clinical observations, body weights, serum chemistry, gross pathology, organ weights, and select tissue histopathology (kidney, lung, liver, thyroid, and tunica vaginalis). Weekly body weight and water consumption means were similar between KBrO₃ and control groups throughout the study. Increases in kidney weights were observed in rats of the 400 mg/L group following 2- or 13-weeks exposure. Hyaline droplets were observed in renal tubules of rats of the 200 and 400 mg/L groups following 2 weeks exposure and in rats of the 400 mg/L group at 13 weeks. There were no KBrO₃-related microscopic findings in the lung, liver, thyroid, and tunica vaginalis at the 2- and 13-week time points. A no observed effect level of 100 mg/L KBrO₃ (8.1 mg/kg/day) was selected based on the absence of microscopic alterations in the kidney.

Topics: Animals; Blood Chemical Analysis; Body Weight; Bromates; Drinking; Endpoint Determination; Kidney; Kidney Diseases; Liver; Male; No-Observed-Adverse-Effect Level; Organ Size; Rats; Rats, Inbred F344; Thyroid Gland

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 300 mg/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 10 mg/kg/day, (2) mild induction of HDN with increased αGST and μGST at 50 mg/kg/day and (3) marked induction of HDN with increased αGST, μGST and albumin at 300 mg/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.

Topics: 1-Propanol; Alpha-Globulins; Animals; Biomarkers; Blood Urea Nitrogen; Bromates; Creatinine; Cyclohexenes; Dose-Response Relationship, Drug; Female; Hyalin; Kidney Diseases; Limonene; Male; Oxidative Stress; Rats; Rats, Wistar; Severity of Illness Index; Terpenes; Time Factors

Rutin, a polyphenolic flavonoid, was investigated for its protective effects against the KBrO(3) induced renal injuries in rat.. Group I was control (untreated), group II was given saline 0.5 ml/kg bw (0.9% NaCl), group III was administered KBrO(3) (20 mg/kg bw) intragastric twice a week for four weeks. Rutin was administered to group VI (50 mg/kg bw) and Group V (70 mg/kg bw) along with KBrO(3) (20 mg/kg bw) while group VI was given rutin (70 mg/kg bw) alone twice a week for four weeks. Protective effects of rutin on KBrO(3)-induced nephrotoxicity in rats were determined for biochemical parameter of urine, and serum, various antioxidant enzymes, DNA and histopathological damages in kidneys.. The level of urinary red blood cells, leucocytes count, specific gravity, urea, creatinine and urobilinogen was increased (P<0.01) whereas creatinine clearance was reduced. Serum level of protein, albumin, globulin, nitrite, creatinine and blood urea nitrogen (BUN) was significantly increased (P<0.01) by KBrO(3). Marked histopathological lesions, elevated DNA fragmentation and AgNORs count in renal tissues was determined. Activity of antioxidant enzymes; catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and reduced glutathione contents were decreased (P<0.01) while thiobarbituric acid reactive substances were increased (P<0.01) with KBrO(3) treatment in kidneys. DNA ladder assay was intimately related with the DNA fragmentation assay. Telomerase activity was found positive in the KBrO(3) treated kidneys. Treatment with rutin effectively ameliorated the alterations in the studied parameters of rat. Rutin administration alone to rats did not exhibit any significant change in any of the parameters studied.. These results suggest that rutin works as an antioxidant in vivo by scavenging reactive oxygen species and this serves to prevent oxidative renal damage in rat treated with KBrO(3).

Topics: Animals; Bromates; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Kidney; Kidney Diseases; Male; Plant Extracts; Protective Agents; Rats; Rats, Sprague-Dawley; Rutin; Superoxide Dismutase

Potassium bromate (KBrO3) is an oxidizing agent used as a food additive which causes kidney damage as a potent nephrotoxic agent, and the mechanism may be explained by the generation of oxygen free radicals. Our experiments showed that single intraperitoneal administration of 200 mg/kg KBrO3 could induce serious kidney damage, with an increase in serum blood urea nitrogen (BUN) and creatinine levels. Five-day oral administration of bilberry ( Vaccinium myrtillus L.) extract at 50, 100, and 200 mg/kg resulted in a reversal in serum BUN and creatinine to normal levels and decreased kidney malondialdehyde (MDA), nitric oxide (NO), and xanthine oxidase (XOD) levels. Also, bilberry extract improved oxygen radical absorbance capacity (ORAC) levels in kidney tissue, which showed that bilberry extract reduced the degree of oxidative stress and kidney damage induced by KBrO3. These findings demonstrate that the protective effect of bilberry extract is attributed to its free radical scavenging activity and lipid peroxidation inhibitory effect.

Topics: Animals; Anthocyanins; Antioxidants; Blood Urea Nitrogen; Bromates; Kidney; Kidney Diseases; Male; Malondialdehyde; Mice; Nitric Oxide; Plant Extracts; Vaccinium myrtillus; Xanthine Oxidase

Various markers derived from radical-mediated oxidative damage to cellular macromolecules have been proposed as tools for the detection of alterations in redox status, but there is strong debate as to which may be the most sensitive and reliable indicator of oxidative stress conditions. This study was aimed to investigate the use of mercapturic acids derived from conjugation of the lipid peroxidation product 4-hydroxy-2(E)-nonenal (HNE) with glutathione and (1)H NMR metabonomics in two rodent models of oxidative kidney damage. Treatment of rats with FeNTA resulted in a marked increase in the concentrations of 4-hydroxy-2(E)-nonenal derived mercapturic acids in plasma and kidney within 5h. 1,4-dihydroxynonenal mercapturic acid (DHN-MA) remained elevated 24h after compound administration, while other markers returned to control levels, suggesting that DHN-MA may present a more stable indicator of lipid peroxidation. However, significant changes were only evident in the presence of severe nephrotoxicity, indicating that HNE-derived mercapturic acids were less sensitive than nonspecific markers of renal injury. In contrast to FeNTA, continuous administration of potassium bromate for 2 weeks had no effect on the concentrations of DHN-MA or 4-hydroxyononenal-3-yl-mercapturic acid in kidney, plasma or urine of treated animals, although a dose-dependent increase in 8-oxo-7,8-dihydro-2'deoxyguanosine was observed in kidney DNA in the absence of nephrotoxicity. These data suggest that markers of lipid peroxidation may not be suitable to detect alterations in redox status induced by potassium bromate at doses known to cause tumors after chronic treatment. Alterations in urine (1)H NMR spectra were detected in both models but reflect nonspecific alterations as a result of impaired renal function rather than specific changes indicative of oxidative stress. In summary, it appears that - depending on the pathological circumstances and the chemical nature of the insult - different types of oxidative stress exist, and it is therefore not possible to define a universal marker of oxidative stress.

Topics: Acetylcysteine; Alanine Transaminase; Aldehydes; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bromates; Creatinine; gamma-Glutamyltransferase; Histocytochemistry; Kidney Diseases; Magnetic Resonance Spectroscopy; Male; Nitrilotriacetic Acid; Oxidative Stress; Principal Component Analysis; Rats; Thiobarbituric Acid Reactive Substances; Urea

Potassium bromate (KBrO(3)) is a by-product from ozonation of high-bromide surface water for production of drinking water and is a rodent carcinogen. Oligonol is a product emanating from the oligomerization of polyphenols, typically proanthocyanidin from a variety of fruits (grapes, apples, persimmons, etc.) and contains catechin-type monomers and proanthocyanidin oligomers. In this study, the ability of oligonol derived from grape seeds, grape seeds extracts (Product A, containing biologically active flavonoids and the oligomeric proanthocyanidin) and pine bark extracts (Product B, composed of flavan-3-ol derivatives) to modulate the KBrO(3)-induced renal toxicity was compared with (+) catechin and (-)-epigallocatechin 3-O-gallate (EGCG). In the Trolox equivalent antioxidant capacity (TEAC) assay, the order of the antioxidant activity was EGCG>catechin>oligonol>Product A>Product B. However, oligonol elicits the strongest antioxidant capacity following in vivo supplementation to rats, with the order of efficacy of oligonol>Product A> or =Product B>EGCG>catechin. Blood levels of lipid peroxidation products (LPO), urea nitrogen (BUN) and creatinine were elevated by KBrO(3) treatment. Oligonol significantly restored LPO to the level in the untreated rats and had the strongest potency when compared with the effects of Products A and B. The five materials lowered KBrO(3)-induced BUN level, but this was not statistically significant. Oligonol significantly reduced the increased level of the creatinine, seconded by Product A, Product B and EGCG. Catechin had the lowest effect in both the BUN and creatinine levels. That oligonol was able to modulate KBrO(3)-induced lipid peroxidation and the levels of blood urea nitrogen and creatinine suggests potential chemopreventive function and application in mitigating toxicity due to long-term exposure to KBrO(3) in public drinking water.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Bromates; Catechin; Creatinine; Flavonoids; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Male; Phenols; Pinus; Polyphenols; Rats; Rats, Wistar; Seeds; Vitis

The aim of the present study was to determine the potential beneficial effects of Ficus racemosa extract. Potassium bromate (KBrO3), a potent nephrotoxic agent that induces renal carcinogenesis and acts as tumour promoter in carcinogen-initiated animals was used as a model to induce renal injury. In this study, we show the chemopreventive effect of Ficus racemosa extract (Moraceae) on KBrO3-mediated renal oxidative stress and cell promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhanced lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content and antioxidant enzymes. KBrO3 treatment also induced tumour promotion markers, viz., ornithine decarboxylase activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with Ficus racemosa extract (200 mg/kg body weight and 400 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P<0.05), lipid peroxidation (P<0.001), gamma-glutamyl transpeptidase (P<0.001) and H(2O2 (P<0.001). There was significant recovery of renal glutathione content (P<0.01) and antioxidant enzymes (P<0.001). There was also reversal in the enhancement of renal ornithine decarboxylase activity, DNA synthesis, blood urea nitrogen and serum creatinine (P<0.001). Our results suggest that Ficus racemosa extract is a potent chemopreventive agent and suppresses KBrO3-mediated nephrotoxicity in rats.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Blood Urea Nitrogen; Bromates; Carcinogens; Cell Proliferation; DNA; Female; Ficus; Glutathione; Kidney; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Ornithine Decarboxylase; Oxidative Stress; Plant Extracts; Rats; Subcellular Fractions

Topics: Animals; Animals, Newborn; Bromates; Bromine; Female; Kidney Diseases; Male; Mice; Mice, Inbred ICR; Neoplasms, Experimental; Rats; Rats, Inbred F344