Toxicity assessment of potassium bromate and the remedial role of grape seed extract.

In this study, the multiple toxic effects of potassium bromate were investigated in Allium cepa L., an indicator test material. In addition, the toxicity-reducing effects of grape seed extract (GSE) were tested. The toxicity was investigated by some physiological (germination percentage, root length, weight gain, relative injury rate), cytogenetic [mitotic index (MI), micronucleus (MN), and chromosomal abnormalities (CAs)], biochemical [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) levels] and anatomical parameters. A. cepa bulbs were divided into 6 groups as control and five treatment groups (Group II: 465 mg/L GSE, Group III: 930 mg/L GSE, Group IV: 100 mg/L potassium bromate, Group V: 100 mg/L potassium bromate + 465 mg/L GSE, Group VI: 100 mg /L potassium bromate + 930 mg/L GSE). The bulbs were germinated for 72 h and at the end of the period the bulbs were subjected to routine preparations and made ready for analysis and measurements. As a result, potassium bromate exposure caused statistically significant (p < 0.05) decreases in all physiological parameter values. Potassium bromate application decreased MI by 41.6%, and increased the MN and CAs frequencies. CAs such as fragment, sticky chromosome, and vagrant chromosome, unequal distribution of chromatin, reverse polarization, nuclear bud and disordered mitosis were induced in root meristem cells. The mechanism of potassium bromate genotoxicity has been associated with DNA-potassium bromate interaction supported by spectral shift. Potassium bromate caused a decrease in GSH levels and an increase in MDA, SOD and CAT levels, thereby disrupting the antioxidant/oxidant balance in root tip cells. GSE administration in two different doses together with potassium bromate reduced the toxic effects and caused improvements in all parameters examined. The most significant reduction in toxicity was in group VI, which received 930 mg/L GSE, and there was an improvement about 18% in MI levels and an improvement about 44% in GSH levels in this group. While GSE application increased physiological parameters and GSH levels, it decreased MDA, SOD, CAT levels, MN and CAs frequencies. As a result, it has been determined that potassium bromate causes multi-directional toxicity at high doses and A. cepa is a very reliable indicator in determining this toxicity. In addition, GSE extract has been found to have a strong role in reducing the toxicity induced by potassium bromate.

Potassium bromate cytotoxicity in the Wister rat model of chronic gastric ulcers: Possible reversal by protocatechuic acid.

The interaction between ingested xenobiotics and the gastrointestinal epithelium influences the possibility of gut epithelial cytotoxicity and systemic toxicity. Potassium bromate (KBrO3 ) has been shown to perturb the central nervous system and it may be carcinogenic, albeit it is used as a food additive. This highlights the need to understand KBrO3 's effect on the stomach epithelium. Here, we report the cytotoxic potential of KBrO3 in an ulcerated stomach, as well as possible cytoprotection by the polyphenol - protocatechuic acid. Potassium bromate (12.5 mg/kg) and protocatechuic acid (120 mg/kg) were administered orally while omeprazole (20 mg/kg) was used as standard. Potassium bromate exacerbated gastric ulcers, increased malonaldehyde levels, catalase, and sodium pump activities, but reduced nitric oxide levels. Potassium bromate further increased mast cell count in the muscularis mucosa, while inducing chronic inflammation and moderate angiogenesis in the gastric mucosa. Our results delineate KBrO3 -induced gastric epithelial cytotoxicity that is ameliorated by protocatechuic acid. PRACTICAL APPLICATIONS: Potassium bromate is a known food additive in the baking, brewing, and cheese-making process. Conversely, protocatechuic acid (3,4-dihydroxybenzoic acid) is the polyphenolic content of plants like Hibiscus sabdariffa L that are commonly consumed as herbal drink, food, spices, and used in folk medicine. This study reports the cytoprotective effect of protocatechuic acid against gastric mucosa ulceration that has been aggravated by potassium bromate.

Dose-response analysis of potassium bromate-induced toxicity in Allium cepa L. meristematic cells.

In this study, the toxic effects of potassium bromate (KBrO3) were tested on Allium cepa L. meristematic cells. In order to determine the toxic effect and dose relationship, KBrO3 toxicity was investigated at doses of 25, 50, and 100 mg/L. The toxic effects were evaluated by using cytogenetic, biochemical, anatomical, and physiological parameters, and serious damages were observed depending on the dose. Significant reductions in germination percentage, weight gain, and radicle length were observed in all KBrO3-treated groups compared with the control. Mitotic activity decreased in meristematic cells after KBrO3 application. and mitotic index was decreased by 1.8 times in 100 mg/L KBrO3-treated group compared with the control group. The frequencies of micronucleus and chromosomal abnormalities tested as cytogenetic parameters were significantly higher in the group treated with 100 mg/L KBrO3 than those in the control group. Fragment and sticky chromosome were the most common types of chromosomal abnormalities. Lipid peroxidation measured in terms of MDA content increased with increasing doses of KBrO3. The activities of catalase and superoxide dismutase as antioxidant enzymes were importantly changed in KBrO3-treated groups. Anatomical changes such as cell deformation, substance accumulation, cell wall thickening, and flattened nucleus were determined after KBrO3 application, and it was observed that these changes reached a maximum level at 100 mg/L dose of KBrO3. As a result, KBrO3 treatments were been found to cause physiological, biochemical, cytogenetic, and anatomically toxic effects in meristematic cells of A. cepa, a eukaryotic model organism. The versatile toxicity induced by KBrO3 increased depending on the dose and reached a maximum level at 100 mg/L.

Deleterious effects of perinatal exposure to potassium bromate on the development of offspring of Swiss mice.

The present study aimed to investigate the impact of perinatal potassium bromate (KBrO3) exposure on the development of sensorimotor reflexes and redox status, and on the histological architecture of the brain, liver, and kidney of newborn mice. Pregnant mice received 1-ml bottled drinking water daily by oral intubation and served as the control group. Another group of pregnant mice were supplemented orally with 200 mg/kg body weight KBrO3 dissolved in drinking water from gestation day 5 to postnatal day 21. KBrO3 induced a decrease in the postnatal body weight in the newborn mice. KBrO3-exposed newborn mice showed poor performance and delayed development of the sensorimotor reflexes. Histological changes, increased lipid peroxidation, and altered antioxidants were reported in the cerebrum, cerebellum, medulla oblongata, liver, and kidney of the KBrO3-exposed newborn mice. In conclusion, these findings demonstrated that perinatal exposure to bromate induced oxidative stress, histological and behavioral alterations, and was a potential teratogen in newborn mice.

Ethanol extract of Curcuma longa rhizome mitigates potassium bromate-induced liver changes in the Wistar rat: Histological, histochemical and immunohistochemical assessments.

The effects of Curcuma longa rhizome on hepatic cells, glycogen, connective tissue fibres and filamentous cytoskeleton were evaluated following KBrO3-induced liver injury in Wistar rats. Thirty-five male rats were randomly divided into seven groups (n=5). Group 1 were normal saline treated rats. Hepatic injury was induced in groups 2 to 7 by oral administration of 100mg/kg KBrO3 for 2 weeks. Following induction, rats in group 2 were sacrificed while groups 3, 4, 5 were given oral dose of EECLOR at 100, 200, 400mg/kg respectively. Group 6 rats were treated with silymarine while group 7 rats were left untreated. The rats were sacrificed and the liver sections were stained with H&E, Masson trichrome, Gordon and Sweets, PAS, Feulgen reaction, anti-vimentin antibody for demonstration of general histoarchitecture, elastic fibre, collagen fibre; glycogen, nuclear DNA and filamentous cytoskeleton respectively. Groups 2, 3, 7 developed intranuclear vacuolation, plasma coagulation, plamolysis, karyopyknosis, karyorrhexis and karyolysis, hyperchromatism, DNA fading and pleomorphism. Immunohistochemical study revealed near negative immunoreaction for vimentin. These pathological changes were ameliorated in EECLOR-treated groups in a manner comparable to silymarine-treated group. The study concluded that ameliorative effects of EECLOR in KBrO3-induced liver injury could be due to its vimentin stabilization property.

Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin.

OBJECTIVE: The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice. METHODS: The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum. RESULTS: We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3. CONCLUSION: Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.

Effect of Launaea procumbens on thyroid glands lipid peroxidation and hormonal dysfunction: a randomized control trial.

BACKGROUND: Launaea procumbens (Roxb.) Amin is traditionally used in Pakistan for the treatment of hormonal disorders and oxidative stress. The present study was aimed to evaluate the efficacy of Launaea procumbens methanol extract (LPME) against KBrO3-induced oxidative stress and hormonal dysfunction in thyroid. METHODS: To examine the effects of LPME against the oxidative stress of KBrO3 in thyroid tissue, 36 male albino rats were used. Protective effects of LPME were observed on thyroid hormonal levels, activities of antioxidant enzymes, lipid peroxidation (TBARS) and DNA damage. RESULTS: Treatment with KBrO3 significantly (P < 0.01) reduced the levels of T3 (55.13 ± 1.93) and T4 (14.7 ± 1.78) and increased TSH (55.13 ± 1.93) levels. KBrO3 exposure in rats reduced the activities of antioxidant enzymes viz.; CAT (1.16 ± 0.08); SOD (12.0 ± 0.08), GST (17.7 ± 1.1) and GSR (54.3 ± 2.1) but increased lipid peroxidation (20.3 ± 0.71) and DNA (30.4 ± 2.0) damage. Co-administration of LPME significantly (P < 0.01) improved these alterations with respect to hormonal levels, activities of antioxidant enzymes and lipid peroxidation close to those seen in control rats. CONCLUSION: These results suggest that LPME can protect thyroid tissue against oxidative damage, possibly through the antioxidant effects of its bioactive compounds.

Protective effects of fraction 4a of polysaccharides isolated from Lycium barbarum against KBrO3-induced renal damage in rats.

Potassium bromate (KBrO3) is widely used as a food additive and is a major by-product of water disinfection. The aim of this study was to investigate the protective effects of fraction 4a of polysaccharides isolated from Lycium barbarum (LBP-4a) against renal damage induced by KBrO3 in rats and to determine the relevant mechanisms behind these effects. Male Wistar rats were divided into a normal control group, a KBrO3 control group, and LBP-4a(L) and LBP-4a(H) groups. With the exception of the normal control group, the rats in the other three groups were administered KBrO3 by intraperitoneal injection to induce renal damage. Before the induction of renal damage, rats in the LBP-4a(L) and LBP-4a(H) groups were pretreated with 50 mg per kg b.w. or 100 mg per kg b.w. LBP-4a, respectively, by intragastric administration. Clinical biochemical parameters and markers of oxidative damage were also determined. Treatment by administration of LBP-4a prior to challenge with KBrO3 prevented increases in the levels of nitrite, creatinine, urea nitrogen and uric acid in serum and increased the activities of antioxidant enzymes in kidney tissues. A comet assay and FCS results showed that pretreatment with LBP-4a also alleviated DNA damage and decreases in mitochondrial membrane potentials in renal cells. Histological studies further supported the above results and showed extensive renal damage in animals treated with KBrO3 and greatly reduced tissue injury in groups pretreated with LBP-4a. In conclusion, LBP-4a exhibited protective effects against renal damage induced by KBrO3, and the mechanism was closely correlated with a reduction in levels of lipid peroxidation and an increase in the activities of antioxidant enzymes in kidney tissues, which alleviated DNA damage and increased mitochondrial membrane potentials in renal cells. These observations provide the background for the further development of LBP-4a as a protective agent for use in the treatment of renal damage.

Flavonoid compounds from the red marine alga Alsidium corallinum protect against potassium bromate-induced nephrotoxicity in adult mice.

Potassium bromate (KBrO3 ), an environmental pollutant, is a well-known human carcinogen and a potent nephrotoxic agent. Currently, natural products have built a well-recognized role in the management of many diseases induced by pollutants. As potent natural sources of bioactive compounds, marine algae have been demonstrated to be rich in novel secondary metabolites with a broad range of biological functions. In this study, adults male mice were orally treated for 15 days with KBrO3 (0.5 g/L) associated or not with extract of Alsidium corallinum, a red Mediterranean alga. In vitro study demonstrated that algal extract has antioxidant efficacy attributable to the presence of flavonoids and polyphenols. Among these, Liquid chromatography-mass spectrometry analysis showed A. corallinum is rich in kaempferol, apigenin, catechin, and quercetin flavonoids. In vivo study showed that supplementation with the alga significantly prevented KBrO3 -induced nephrotoxicity as indicated by plasma biomarkers (urea, uric acid, and creatinin levels) and oxidative stress related parameters (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C, hydrogen peroxide, protein oxidation products) in kidney tissue. The corrective effect of A. corallinum on KBrO3 -induced kidney injury was also supported by molecular and histopathological observations. In conclusion, it was established that the red alga, thanks to its bioactive compounds, effectively counteracts toxic effects of KBrO3 and could be a useful coadjuvant agent for treatment of this pollutant poisonings. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1475-1486, 2017.

Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice.

BACKGROUND: Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. METHODS: Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. RESULTS: Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. CONCLUSIONS: These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.

Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts.

BACKGROUND: Exposure to bisphenol A (BPA) has been reported to alter global gene expression, induce epigenetic modifications, and interfere with complex regulatory networks of cells. In addition to these reprogramming events, we have demonstrated that BPA exposure generates reactive oxygen species and promotes cellular survival when co-exposed with the oxidizing agent potassium bromate (KBrO3). OBJECTIVES: We determined the cellular microenvironment changes induced by co-exposure of BPA and KBrO3 versus either agent alone. METHODS: Ku70-deficient cells were exposed to 150 µM BPA, 20 mM KBrO3, or co-exposed to both agents. Four and 24 hr post-damage initiation by KBrO3, with BPA-only samples timed to coincide with these designated time points, we performed whole-genome microarray analysis and evaluated chromatin structure, DNA lesion load, glutathione content, and intracellular pH. RESULTS: We found that 4 hr post-damage initiation, BPA exposure and co-exposure transiently condensed chromatin compared with untreated and KBrO3-only treated cells; the transcription of DNA repair proteins was also reduced. At this time point, BPA exposure and co-exposure also reduced the change in intracellular pH observed after treatment with KBrO3 alone. Twenty-four hours post-damage initiation, BPA-exposed cells showed less condensed chromatin than cells treated with KBrO3 alone; the intracellular pH of the co-exposed cells was significantly reduced compared with untreated and KBrO3-treated cells; and significant up-regulation of DNA repair proteins was observed after co-exposure. CONCLUSION: These results support the induction of an adaptive response by BPA co-exposure that alters the microcellular environment and modulates DNA repair. Further work is required to determine whether BPA induces similar DNA lesions in vivo at environmentally relevant doses; however, in the Ku70-deficient mouse embryonic fibroblasts, exposure to a high dose of BPA was associated with changes in the cellular microenvironment that may promote survival. CITATION: Gassman NR, Coskun E, Jaruga P, Dizdaroglu M, Wilson SH. 2016. Combined effects of high-dose bisphenol A and oxidizing agent (KBrO3) on cellular microenvironment, gene expression, and chromatin structure of Ku70-deficient mouse embryonic fibroblasts. Environ Health Perspect 124:1241-1252; http://dx.doi.org/10.1289/EHP237.

Ameliorative effects of vanillin on potassium bromate induces bone and blood disorders in vivo.

The objective of this study was to investigate the propensity of potassium bromate (KBrO3) to induce oxidative stress in blood and bone of adult mice and its possible attenuation by vanillin. Our results demonstrated, after KBrO3 treatment, a decrease of red blood cells and hemoglobin and a significant increase of white blood cell. A decrease in plasma levels of folic acid, vitamin B12 and iron was also noted. Interestingly, an increase of lipid peroxidation, hydroperoxides, hydrogen peroxide, advanced oxidation protein products and protein carbonyl levels in erythrocytes and bone was observed, while superoxide dismutase, catalase and glutathione peroxidase activities and glutathione, non-protein thiol and vitamin C levels were decreased. KBrO3 treatment resulted in blood and bone DNA fragmentation, a hallmark of genotoxicity-KBrO3-induced, with reduction of DNA levels. Calcium and phosphorus levels showed a decrease in the bone and an increase in the plasma after KBrO3 treatment. These biochemical alterations were accompanied by histological changes in the blood smear and bone tissue. Treatment with vanillin improved the histopathological, hematotoxic and genotoxic effects induced by KBrO3. The results showed, for the first time, that the vanillin possesses a potent protective effect against the oxidative stress and genotoxicity in bone and blood of KBrO3-treated mice.

Protective effects of Sonchus asper against KBrO3 induced lipid peroxidation in rats.

BACKGROUND: Sonchus asper is traditionally used in Pakistan for the treatment of reproductive dysfunction and oxidative stress. The present investigation was aimed to evaluate chloroform extract of Sonchus asper (SACE) against potassium bromate-induced reproductive stress in male rats. METHODS: 20 mg/kg body weight (b.w.) potassium bromate (KBrO3) was induced in 36 rats for four weeks and checked the protective efficacy of SACE at various hormonal imbalances, alteration of antioxidant enzymes, and DNA fragmentation levels. High performance chromatography (HPLC) was used for determination of bioactive constituents responsible. RESULTS: The level of hormonal secretion was significantly altered by potassium bromate. DNA fragmentation%, activity of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and phase II metabolizing enzymes viz; glutathione reductase (GSR), glutathione peroxidase (GSHpx), glutathione-S-tansase (GST) and reduced glutathione (GSH) was decreased while hydrogen per oxide contents and thiobarbituric acid reactive substances (TBARS) were increased with KBrO3 treatment. Treatment with SACE effectively ameliorated the alterations in the biochemical markers; hormonal and molecular levels while HPLC characterization revealed the presence of catechin, kaempferol, rutin and quercetin. CONCLUSION: Protective effects of Sonchus asper vs. KBrO3 induced lipid peroxidation might be due to bioactive compound present in SACE.

Protective effects of rutin against potassium bromate induced nephrotoxicity in rats.

BACKGROUND: Rutin, a polyphenolic flavonoid, was investigated for its protective effects against the KBrO(3) induced renal injuries in rat. METHODS: 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. RESULTS: 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. CONCLUSION: 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).

Lack of mutagenic and toxic effects of low dose potassium bromate on kidneys in the Big Blue rat.

Potassium bromate (KBrO3) has been classified as a genotoxic carcinogen based on positive results in the Ames test, and chromosome aberration and micronucleus tests. The purpose of the present study was to investigate the dose-response relationship for in vivo mutagenic and toxic effects of KBrO3 in the kidneys of Big Blue rats. In experiment 1, male Big Blue rats were divided into 8 groups. KBrO3 was dissolved in tap water and administered to groups 1-8 at concentrations of 0, 0.02, 0.2, 2, 8, 30, 125 and 500 ppm, respectively, for 16 weeks. Experiment 2 was performed to investigate the effects of KBrO3 at the 0.002 ppm dose approximately contained in the tap water on rat kidneys. Ten Big Blue rats were divided into 2 groups and given distilled water and tap water, respectively, for 16 weeks. In experiment 1, treatment with 500 ppm KBrO3 significantly increased the mutant and total mutation frequencies and frequency of GC to TA transversion of the lacI gene in the kidney compared to non-treatment control group, but 125 ppm and lower doses of KBrO3 had no effects. Histopathologically, renal toxic changes were observed in groups administered KBrO3 at 30 ppm or higher in a dose-dependent manner. PCNA positive cell indices in renal tubular cells were significantly increased in the kidney at doses of 125 and 500 ppm, but not at 30 ppm or lower doses, as compared to the control group. Furthermore, 8-hydroxy-2'-deoxyguanosine formation, a marker of oxidative stress, was significantly increased at 500 ppm. In experiment 2, there were no differences in any parameter between the distilled water and tap water groups. These results suggest the existence of no-effect levels for in vivo mutagenic and toxic effects, proliferation stimulus, and oxidative stress of KBrO3 in rat kidneys.

Protective effects of bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced kidney damage in mice.

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.

Comparative efficacy of oligonol, catechin and (-)-epigallocatechin 3-O-gallate in modulating the potassium bromate-induced renal toxicity in rats.

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.

Bromate-induced ototoxicity.

For decades, it has been known that ingested potassium bromate and sodium bromate can induce hearing loss. Hearing loss onset, following high-dose ingestion, is generally rapid occurring within 4-16 h and of a severe to profound degree. Unlike the sensorineural hearing loss which is generally irreversible, bromate-induced tinnitus, which is less well-studied, may reportedly be permanent or temporary. It is not clear whether actual bromate-induced vestibulotoxicity occurs in clinical populations. The primary sites of lesion for bromate-induced ototoxicity appear to be in the cochlea. However, possible effects on the VIIIth nerve and central auditory system have not been fully investigated. Based on animal studies, in the cochlea, bromate damages the stria vascularis, Reissner's membrane, inner and outer hair cells, Claudius cells and inner sulcus cells. Physiologically, bromate reduces the endocochlear potential, cochlear microphonics, and electrophysiologic auditory thresholds. Possible mechanisms are discussed. The effects of long-term low-dose bromate exposure on hearing have not been studied. These effects, if they occur, may not be readily detected in many clinical populations, because idiopathic hearing loss occurs commonly in the population as a whole. Further it is unknown whether or not chronic bromate ingestion may exacerbate noise-induced hearing loss. Further study to determine the maximum safe exposure level for long-term administration and to develop possible antidotes is warranted.

Modulatory effect of Ficus racemosa: diminution of potassium bromate-induced renal oxidative injury and cell proliferation response.

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.

Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant.

Metallothionein (MT) demonstrates strong antioxidant properties, yet the physiological relevance of its antioxidant action is not clear. Injection of mice with ferric nitrilotriacetate (Fe-NTA) caused a dose-dependent increase in hepatic and renal MT. Fe-NTA caused a greater increase in hepatic and renal MT concentration (2.5- and 4-fold) compared with FeCl(3) at the same dose of ferric ion. MT mRNA levels were markedly elevated in both of tissues. Thiobarbituric acid (TBA) values in both tissues reached a maximum after 2-4 h. The MT concentrations were significantly increased after 2-4 h in liver and after 8-16 h in kidneys. Plasma concentrations of cytokines such as IL-6 and TNFalpha were elevated by 4 h; IL-6 levels were 24 times higher after Fe-NTA than that after injection of FeCl(3). Pretreatment of mice with ZnSO(4) attenuated nephrotoxicity induced by Fe-NTA after 2 h, but was not effective 4 h after injection. After a Fe-NTA injection, a loss of Cd-binding properties of preinduced MT was observed only in kidneys of Zn-pretreated mice but not in liver. Treatment with BSO, glutathione (GSH) depletor, intensified a loss of its Cd-binding properties after a Fe-NTA injection. These results indicate that induction of MT synthesis may result from reactive oxygen species (ROS) generated by Fe-NTA, and MT may act in vivo as a complementary antioxidant.