Zinc Oxide Nanoparticles Blunt Potassium-Bromate-Induced Renal Toxicity by Reinforcing the Redox System.

Potassium bromate (PB) is a general food additive, a significant by-product during water disinfection, and a carcinogen (Class II B). The compound emits toxicity depending on the extent of its exposure and dose through consumable items. The current study targeted disclosing the ameliorative efficacy of zinc oxide nanoparticles (ZnO NPs) prepared by green technology in PB-exposed Swiss albino rats. The rats were separated into six treatment groups: control without any treatment (Group I), PB alone (Group II), ZnO alone (Group III), ZnO NP alone (Group IV), PB + ZnO (Group V), and PB + ZnO NPs (Group VI). The blood and kidney samples were retrieved from the animals after following the treatment plan and kept at -20 °C until further analysis. Contrary to the control (Group I), PB-treated rats (Group II) exhibited a prominent trend in alteration in the established kidney function markers and disturbed redox status. Further, the analysis of the tissue and nuclear DNA also reinforced the biochemical results of the same treatment group. Hitherto, Groups III and IV also showed moderate toxic insults. However, Group VI showed a significant improvement from the PB-induced toxic insults compared to Group II. Hence, the present study revealed the significant therapeutic potential of the NPs against PB-induced nephrotoxicity in vivo, pleading for their usage in medicines having nephrotoxicity as a side effect or in enhancing the safety of the industrial use of PB.

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-induced oxidative stress, genotoxicity and cytotoxicity in the blood and liver cells of mice.

Potassium bromate (KBrO3) is an oxidising agent that is extensively used as a food additive, it is also a product of cosmetic and pharmaceutical relevance. The objective of this study was to evaluate the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. To study the toxic effects and oxidative stress, different doses of KBrO3 below LD50 (The half maximal lethal dose, 50, 100 and 150 mg/kg body weight) were given intraperitoneally to the mice for multiple time periods (24, 48, and 72 h). The results showed that KBrO3 significantly induces oxidative damage by increasing the levels of reactive oxygen species (ROS) and lipid peroxidase and depleted the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzymes in the serum and liver. Moreover, a significant increase of chromosomal aberrations in bone marrow cells and an elevated incidence of micronuclei in the peripheral blood of mice were observed. KBrO3 induces 3 ´ -OH end double-strand DNA breaks, which was evident in liver sections of the treated mice, and increases the percentage of apoptotic cells, as observed in TUNEL assays and flow cytometry analysis. The present findings indicate that KBrO3 induces oxidative stress, genotoxicity, and cytotoxicity in a dose- and time-dependent manner in mice.

New aspects in deriving health-based guidance values for bromate in swimming pool water.

Bromate, classified as a EU CLP 1B carcinogen, is a typical by-product of the disinfection of drinking and swimming pool water. The aim of this study was (a) to provide data on the occurrence of bromate in pool water, (b) to re-evaluate the carcinogenic MOA of bromate in the light of existing data, (c) to assess the possible exposure to bromate via swimming pool water and (d) to inform the derivation of cancer risk-related bromate concentrations in swimming pool water. Measurements from monitoring analysis of 229 samples showed bromate concentrations in seawater pools up to 34 mg/L. A comprehensive non-systematic literature search was done and the quality of the studies on genotoxicity and carcinogenicity was assessed by Klimisch criteria (Klimisch et al., Regul Toxicol Pharmacol 25:1-5, 1997) and SciRAP tool (Beronius et al., J Appl Toxicol, 38:1460-1470, 2018) respectively. Benchmark dose (BMD) modeling was performed using the modeling average mode in BMDS 3.1 and PROAST 66.40, 67 and 69 (human cancer BMDL10; EFSA 2017). For exposure assessment, data from a wide range of sources were evaluated for their reliability. Different target groups (infants/toddlers, children and adults) and exposure scenarios (recreational, sport-active swimmers, top athletes) were considered for oral, inhalation and dermal exposure. Exposure was calculated according to the frequency of swimming events and duration in water. For illustration, cancer risk-related bromate concentrations in pool water were calculated for different target groups, taking into account their exposure using the hBMDL10 and a cancer risk of 1 in 100,000. Convincing evidence was obtained from a multitude of studies that bromate induces oxidative DNA damage and acts as a clastogen in vitro and in vivo. Since statistical modeling of the available genotoxicity data is compatible with both linear as well as non-linear dose-response relationships, bromate should be conservatively considered to be a non-threshold carcinogen. BMD modeling with model averaging for renal cancer studies (Kurokawa et al., J Natl. Cancer Inst, 1983 and 1986a; DeAngelo et al., Toxicol Pathol 26:587-594, 1998) resulted in a median hBMDL10 of 0.65 mg bromate/kg body weight (bw) per day. Evaluation of different age and activity groups revealed that top athletes had the highest exposure, followed by sport-active children, sport-active adults, infants and toddlers, children and adults. The predominant route of exposure was oral (73-98%) by swallowing water, followed by the dermal route (2-27%), while the inhalation route was insignificant (< 0.5%). Accepting the same risk level for all population groups resulted in different guidance values due to the large variation in exposure. For example, for an additional risk of 1 in 100,000, the bromate concentrations would range between 0.011 for top athletes, 0.015 for sport-active children and 2.1 mg/L for adults. In conclusion, the present study shows that health risks due to bromate exposure by swimming pool water cannot be excluded and that large differences in risk exist depending on the individual swimming habits and water concentrations.

Effects of bromate on life history parameters, swimming speed and antioxidant biomarkers in Brachionus calyciflorus.

The baking industries and disinfection of tap water released a considerable amount of bromate into surface water, which has been reported as a carcinogenic compound to mammals. Rotifers play an important role in freshwater ecosystems and are model organisms to assess environmental contamination. In the present study, the effects of different concentrations (0.001, 0.01, 0.1, 1, 10, 100 and 200 mg/L) of bromate on the life-table and population growth parameters were investigated in the rotifer Brachionus calyciflorus. The results showed that the 24-h LC50 of bromate to B. calyciflorus was 365.29 mg/L (95%Cl: 290.37-480.24). Treatments with 0.01, 10 and 200 mg/L bromate shorten the reproductive period. High levels of bromate (100 and 200 mg/L) significantly decreased net reproductive rate, intrinsic rate of population increase, life span, mictic rate of B. calyciflorus. To investigate the underlying mechanisms, swimming speed and antioxidative biomarkers were compared between bromate treatments and the control. The results showed that glutathione (GSH) and malondialdehyde (MDA) contents, total superoxide dismutase (T-SOD) and peroxidase (POD) activities decreased significantly in response to bromate exposure and the reasons required further investigation. Treatments with 0.001-200 mg/L bromate all significantly reduced swimming linear speed to rotifer larvae and treatments with 100-200 mg/L bromate significantly suppressed the swimming linear speed of adult rotifer. These changes would reduce filtration of algal food and could explain the decreased survival and reproduction. Overall, bromate may not show acute toxicity to rotifers, but still have potential adverse effects on rotifer behavior, which may then influence the community structure in aquatic ecosystems.

Potassium bromate-induced cell model of age-related macular degeneration in vitro.

Age­related macular degeneration (AMD) progression occurs due to oxidative stress in retinal pigment epithelium (RPE) cells. To develop a new model of AMD, the present study investigated the effects of potassium bromate (KBrO3) on ARPE­19 cells. Incubation with KBrO3 for 24 h significantly decreased ARPE­19 cell viability in a concentration­dependent manner compared with the control group. The MTT and lactate dehydrogenase assay results indicated that KBrO3 induced cell apoptosis. Compared with the control group, KBrO3 treatment significantly decreased the Bcl2/Bax ratio, as determined via western blotting, and caspase­3 mRNA expression levels. Fluorescence microscopy indicated the increased ROS levels in cells treated with KBrO3. Endogenous antioxidant enzyme activities, including superoxide dismutase and glutathione peroxidase, were significantly inhibited by KBrO3 compared with the control group. Moreover, the antioxidants tiron and phloroglucinol inhibited KBrO3­mediated effects on ARPE­19 cells in a dose­dependent manner. Additionally, GPR109A is the binding site of 4­hydroxynonenal (4­HNE). KBrO3 displayed cytotoxic effects in 293 cells, which naturally lack the GPR109A gene, but these effects were not observed in 4­HNE­treated 293 cells, suggesting that KBrO3 induced apoptosis without increasing endogenous 4­HNE levels in cells. Moreover, the results suggested that KBrO3­induced oxidative stress may activate STAT3 to increase VEGF expression in ARPE­19 cells. Collectively, the results of the present study supported the potential use of KBrO3 to induce an in vitro model of AMD in ARPE­19 cells.

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.

The Alleviative Effect of Vitamin B2 on Potassium Bromate-Induced Hepatotoxicity in Male Rats.

Potassium bromate (PB) is a food enhancer, water disinfection by-product, and a proven carcinogen. It elicits toxicities in the living organism due to exposure and in a dose-dependent manner. The present study discourses the ameliorative efficacy of riboflavin (RF) in PB-administered rodents. The animals were distributed into five treatment groups: control (group I), PB alone (group II, 150 mg/kg), RF alone (group III, 2 mg/kg), PB+RF1 (group IV, 150 mg/kg + 2 mg/kg), and PB+RF2 (group V, 150 mg/kg + 4 mg/kg). After the round of the treatment, the animals were sacrificed to collect their blood and liver samples for the detailed analysis. Group II depicted perturbed liver functions evidenced by altered serum and toxicity markers along with the disturbed redox balance. Also, these biochemical results were found harmonious with histopathological analysis and comet assay. However, group III showed no noticeable alteration in the same parameters, whereas the combination groups (IV and V) exhibited dose-dependent amelioration in the PB-induced toxicities. Interestingly, RF favored apoptosis concomitant with suppressing the necrosis in the PB-challenged groups, as shown by the activity of caspase-3 and lactate dehydrogenase. Histopathological analysis and comet assay further consolidate these results. Hence, RF has significant alleviative property against PB-induced hepatotoxicity in vivo that can be used in the consumer items containing the toxicant.

Chemopreventive effect of riboflavin on the potassium bromate-induced renal toxicity in vivo.

Potassium bromate (PB) is a general food additive, flavor enhancer, a by-product of water disinfection, and a class 2 carcinogen. It exerts various toxic effects in a dose- and time-dependent manner in vivo. This study is to explore the chemopreventive efficacy of vitamin B2 (riboflavin, RF) in PB-administered Swiss albino rats. The rats were distributed into five groups: control (group 1), PB alone (group 2, 150 mg/kg), RF alone (group 3, 2 mg/kg), PB + RF1 (group 4, 150 and 2 mg/kg), and PB + RF2 (group 5, 150 and 4 mg/kg). All the rodents were sacrificed after the completion of the treatment cycle. Then, blood and kidney samples were subjected to biochemical analysis. Group 2 demonstrated vivid signs of renal toxicities evidenced by altered renal function markers (urea, creatinine, albumin, glutathione-S-transferase) and redox status parameters (superoxide dismutase, catalase, glutathione reductase, reduced glutathione, lipid, and protein oxidation products). However, group 3 exhibited a slight alteration in many of the parameters while groups 4 and 5 demonstrated dose-dependent chemopreventive efficiency of RF against PB-induced alterations. Besides, RF seemed to facilitate apoptosis as well as inhibition of the necrosis in the PB-pre-challenged groups, as demonstrated by the cleaved PARP and lactate dehydrogenase activity. Also, the histopathological analysis and comet assay validate the biochemical results of the treatment groups significantly. All these results plead that RF has a significant chemopreventive property against PB-induced toxicity in vivo. Therefore, RF is a suitable agent in preventing the PB-induced toxicities at the clinical and industrial levels.

Potassium bromate as positive assay control for the Fpg-modified comet assay.

The comet assay is a popular assay in biomonitoring studies. DNA strand breaks (or unspecific DNA lesions) are measured using the standard comet assay. Oxidative stress-generated DNA lesions can be measured by employing DNA repair enzymes to recognise oxidatively damaged DNA. Unfortunately, there has been a tendency to fail to report results from assay controls (or maybe even not to employ assay controls). We believe this might have been due to uncertainty as to what really constitutes a positive control. It should go without saying that a biomonitoring study cannot have a positive control group as it is unethical to expose healthy humans to DNA damaging (and thus potentially carcinogenic) agents. However, it is possible to include assay controls in the analysis (here meant as a cryopreserved sample of cells i.e. included in each experiment as a reference sample). In the present report we tested potassium bromate (KBrO3) as a positive comet assay control for the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. Ten laboratories used the same procedure for treatment of monocytic THP-1 cells with KBrO3 (0.5, 1.5 and 4.5 mM for 1 h at 37°C) and subsequent cryopreservation. Results from one laboratory were excluded in the statistical analysis because of technical issues in the Fpg-modified comet assay. All other laboratories found a concentration-response relationship in cryopreserved samples (regression coefficients from 0.80 to 0.98), although with different slopes ranging from 1.25 to 11.9 Fpg-sensitive sites (%DNA in tail) per 1 mM KBrO3. Our results demonstrate that KBrO3 is a suitable positive comet assay control.

Oxidative-stress-driven mutagenesis in the small intestine of the gpt delta mouse induced by oral administration of potassium bromate.

Tumorigenesis induced by oxidative stress is thought to be initiated by mutagenesis, but via an indirect mechanism. The dose-response curves for agents that act by this route usually show a threshold, for unknown reasons. To gain insight into these phenomena, we have analyzed the dose response for mutagenesis induced by the oral administration of potassium bromate, a typical oxidative-stress-generating agent, to gpt delta mice. The agent was given orally for 90 d to either Nrf2+ or Nrf2-knockout (KO) mice and mutants induced in the small intestine were analyzed. In Nrf2+mice, the mutant frequency was significantly greater than in the vehicle controls at a dose of 0.6 g/L but not at 0.2 g/L, indicating that a practical threshold for mutagenesis lies between these doses. At 0.6 g/L, the frequencies of G-to-T transversions (landmark mutations for oxidative stress) and G-to-A transitions were significantly elevated. In Nrf2-KO mice, too, the total mutant frequency was increased only at 0.6 g/L. G-to-T transversions are likely to have driven tumorigenesis in the small intestine. A site-specific G-to-T transversion at guanine (nucleotide 406) in a 5'-TGAA-3' sequence in gpt, and our primer extension reaction showed that formation of the oxidative DNA base modification 8-oxo-deoxyguanosine (8-oxo-dG) at nucleotide 406 was significantly increased at doses of 0.6 and 2 g/L in the gpt delta mice. In the Apc oncogene, guanine residues in the same or similar sequences (TGAA or AGAA) are highly substituted by thymine (G-to-T transversions) in potassium bromate-induced tumors. We propose that formation of 8-oxo-dG in the T(A)GAA sequence is an initiating event in tumor formation in the small intestine in response to oxidative stress.

Potassium bromate: Effects on bread components, health, environment and method of analysis: A review.

Potassium bromate, is an oxidizing agent and one of the best and cheapest dough improvers in the baking industry. Due to its positive effects it plays a major role in the bread-making industry. Potassium bromate has significant effect on food biomolecules, such as starch and protein, as it affects the extent of gelatinization, viscosity, swelling characteristics as well as gluten proteins; it removes the sulfhydryl group and leads to the formation of disulfide linkages and thus improves the bread properties. However, there are many reports elucidating its negative impact on human health. It is deemed as a potential human carcinogen by IARC and classified under class 2B. Due to this, countries across world have either partially or completely banned it. Numerous techniques have evolved to determine the concentration of potassium bromate in bread. This review explains in detail, the effects of potassium bromate on biomolecules, human health, environment and various methods of analysis.

Ameliorative effect of zinc oxide nanoparticles against potassium bromate-mediated toxicity in Swiss albino rats.

Potassium bromate (PB) is a commonly used food additive, a prominent water disinfection by-product, and a class IIB carcinogen. It exerts a various degree of toxicity depending on its dose and exposure duration consumed with food and water in the living organisms. The present investigation aims to demonstrate the protective efficacy of zinc oxide nanoparticles (ZnO NPs) derived from Ochradenus arabicus (OA) leaf extract by green technology in PB-challenged Swiss albino rats. The rodents were randomly distributed, under the lab-standardized treatment strategy, into the following six treatment groups: control (group I), PB alone (group II), ZnO alone (group III), ZnO NP alone (group IV), PB + ZnO (group V), and PB + ZnO NPs (group VI). The rats were sacrificed after completion of the treatment, and their blood and liver samples were collected for further analysis. Group II showed extensive toxic effects with altered liver function markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, glutathione-S-transferase, and thioredoxin reductase) and compromised redox status (SOD, CAT, GR, GPx, GSH, MDA, and total carbonyl content). The histopathological analysis and comet assay further supported the biochemical results of the same group. Besides, group III also showed moderate toxicity evidenced by an alteration in most of the studied parameters while group IV demonstrated mild toxicity after biochemical analysis indicating the excellent biocompatibility of the NPs. However, group VI exhibited attenuation of the PB-induced toxic insults to a significant level as compared to group II, whereas group V failed to show similar improvement in the studied parameters. All these findings entail that the ZnO NPs prepared by green synthesis have significant ameliorative property against PB-induced toxicity in vivo. Moreover, administration of the NPs improved the overall health of the treated animals profoundly. Hence, these NPs have significant therapeutic potential against the toxic effects of PB and similar compounds in vivo, and they are suitable to be used at the clinical and industrial levels.

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.

Impact of DNA polymerase ζ mutations on genotoxic thresholds of oxidative mutagens.

In regulatory genetic toxicology, it is an axiom that there is no threshold for genotoxicity of chemicals, such that genotoxic chemicals may impose carcinogenic risk on humans even at very low doses. This paradigm is counterintuitive, however, because humans possess a number of self-defense mechanisms that may suppress the genotoxicity at these low doses and therefore manifest a practical threshold. DNA polymerase zeta (Pol ζ) is a specialized Pol that plays an important role in DNA synthesis across DNA damage, thereby modulating cell survival and genotoxicity. In this study, we compared the sensitivity of three types of human cells: D2781N, L2618M, and their wild-type (WT) cells, to the low dose effects of genotoxicity of the oxidizing agents, potassium bromate (KBrO3) and sodium dichromate (Na2Cr2O7). D2781N cells express a variant form of Pol ζ, whose activity is weaker than that of the WT enzyme. L2618M cells express another variant form of Pol ζ, whose fidelity of DNA replication is lower than that of the WT enzyme. D2781N exhibited the highest sensitivity for TK gene mutation and micronucleus (MN) formation and displayed the lowest practical threshold for MN induction by KBrO3. In contrast, L2618M exhibited the lowest practical threshold for sister-chromatid exchange (SCE) induction by both chemicals. These results suggest that Pol ζ mutations have significant impacts on practical thresholds of genotoxicity; the factors affecting the practical threshold can differ depending on the endpoint of genotoxicity. Roles of the variant forms of Pol ζ in genotoxicity by the oxidizing agents are discussed.

Effects of vanillin on potassium bromate-induced neurotoxicity in adult mice: impact on behavior, oxidative stress, genes expression, inflammation and fatty acid composition.

CONTEXT: Vanillin is known to possess important antioxidant activity. OBJECTIVE: The current study was conducted to establish the therapeutic efficiency of vanillin against potassium bromate (KBrO3)-induced depression-like behavior and oxidative stress in mice. MATERIAL AND METHODS: Mice were exposed during 15 days either to potassium bromate (KBrO3), KBrO3+ vanillin or to only vanillin. RESULTS: Our results revealed a significant modification in the fatty acid composition of the KBrO3-treated mice. In addition, KBrO3 induced a significant reduction in enzymatic activities and gene expressions, Na+ -K+ and Mg2+-ATPases, acetylcholinesterase and butylcholinesterase activities. The gene expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6 and COX2, significantly increased in the cerebrum of KBrO3-treated group. Histopathological observations were consistent with these effects. Co-treatment with vanillin significantly attenuated KBrO3-induced oxidative stress and inflammation. CONCLUSION: This work suggests that vanillin mitigates KBrO3-induced depression, and that this neuroprotective effect proceeds through anti-oxidant and anti-inflammatory activities.

Valorization of aluminum scrap via an acid-washing treatment for reductive removal of toxic bromate from water.

Aluminum scrap (AS) is adopted for the first time as a readily available aluminum source to prepare zero-valent aluminum (ZVAl) for removing bromate from water via a reductive reaction. Since aluminum is easily oxidized to aluminum oxide (Al2O3) on exposure to air, an acid-washing pretreatment on AS is developed to remove the layer of Al2O3. HCl is found as the most effective acid to pretreat AS and the HCl-pretreated or acid-washed AS (AWAS) is able to remove bromate from water and convert it to bromide. Factors, such as temperature, pH, co-existing anions, and particle size, which influence the bromate removal using AWAS are also investigated. The mechanism of bromate removal by AWAS can be attributed to both reduction and adsorption. The elevated temperature also significantly improves bromate removal capacity of AWAS as well as the reaction kinetics. The bromate removal capacity of AWAS is substantially improved under acidic conditions. However, the basic conditions and co-existing anions suppress or interfere with the interaction between bromate and AWAS, leading to much lower removal capacities. The recyclability of AWAS is also evaluated and the acid-washing regeneration is necessary to restore its capacity. However, the mass of AWAS can gradually decrease due to multi-cycle acid-washing regeneration. Through this study, the valorization of AS via acid-washing is demonstrated and optimization of acid-washing parameters is presented. Our findings reveal that the acid-washing is a useful technique to utilize AS as an inexpensive and efficient material for removing bromate from water.

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.

BUBR1 Insufficiency in Mice Increases their Sensitivity to Oxidative Stress.

BACKGROUND/AIM: Budding uninhibited by benzimidazole-related 1 (BUBR1) plays an important role in the spindle assembly checkpoint to prevent chromosome missegregation and aneuploidy during mitosis. We previously generated mutant mice that express BUBR1 at only 20% of the normal level (BubR1L/L mice). Here, we examined the effect of low BUBR1 expression on oxidative stress-induced carcinogenesis in mice. MATERIALS AND METHODS: We orally administered either a potassium bromate (KBrO3) solution (2 g/l) or tap water to BubR1L/L and wild-type (BubR1+/+)mice for 16 weeks and examined the subsequent incidence of tumours. RESULTS: KBrO3-treated BubR1L/L mice showed significantly higher mortality than the KBrO3-treated BubR1+/+ and control tap water-treated mice (p=0.0082). Histopathological and immunohistochemical analyses revealed that the spleens of surviving BubR1L/L mice were occupied by non-B-, non-T-cells with high proliferative potential. CONCLUSION: Our results indicate that low BUBR1 expression increases oxidative stress-induced mortality in mice, possibly caused by splenic neoplasms.

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.