Joseph A. Adeyemi

Teratogenicity, genotoxicity and oxidative stress in zebrafish embryos (Danio rerio) co-exposed to arsenic and atrazine

Arsenic and atrazine are common environmental contaminants probably due to their extensive use as pesticides on agricultural farmlands. In this study, zebrafish embryos were exposed to 0.8mM arsenic, 0.1mM atrazine or mixture of both for 96h, and various indices which are indicative of teratogenicity (egg coagulation, growth retardation, edema formation, hatching success, scoliosis), genotoxicity (DNA tail moments) and oxidative stress (lipid peroxidation and reduced glutathione (GSH) levels, catalase and glutathione peroxidase activities) were determined. The negative control were exposed to 0.5% DMSO while the positive control group were exposed to 4mg/L 3,4 dichloroaniline. Egg coagulation was highest in the positive control (85%), followed by the group that was exposed to mixture of arsenic and atrazine (30%) and least in the arsenic-exposed group (20%). The incidences of edema (59%) and growth retardation (35.2%) were more frequent in the group that was exposed to contaminant mixture and least in atrazine-exposed group where incidences of both edema and growth retardation were 15%. The incidence of scoliosis ranged between 20% in arsenic-exposed group and 10% in atrazine-exposed group. Hatching success was generally high in all the groups ranging between 95% in atrazine-exposed group and 88% in the group that was exposed to mixture of arsenic and atrazine. There was no evidence of teratogenic effect in the negative control group. DNA tail moments and lipid peroxidation levels increased significantly while GSH levels and catalase activity decreased significantly in contaminant-exposed groups, especially the mixture compared to the negative control. There was no significant change in GPx activity in the exposed groups compared to the negative control. The results of this study demonstrate that both arsenic and atrazine are potentially teratogenic and genotoxic, and can cause oxidative stress in zebrafish embryos, and these effects are potentiated by toxic interactions between the two contaminants.

Effects of genetic polymorphisms on antioxidant status and concentrations of the metals in the blood of riverside Amazonian communities co-exposed to Hg and Pb.

There have been reports of genetic effects affecting the metabolism of Hg and Pb individually, and thus modulating their toxicities. However, there is still a knowledge gap with respect to how genetics may influence the toxicities of these toxic metals during a co-exposure scenario. This present study is therefore aimed at investigating the effects of polymorphisms in genes (GSTM1, GSTT1, GSTP1, GCLM, GCLC, GPx1, ALAD, VDR and MDR1) that have been implicated in Hg and Pb metabolisms affects the kinetics of these metals, as well as various blood antioxidant status parameters: MDA and GSH, and the activities of CAT, GPx and ALAD among populations that have been co-exposed to both Hg and Pb. Study subjects (207 men; 188 women) were from an Amazonian population in Brazil, exposed to Hg and Pb from diet. The blood levels of Hg and Pb were determined by ICP-MS while genotyping were performed by PCR assays. The median values of Hg and Pb in blood were 39.8µg/L and 11.0µg/dL, respectively. GSTM1, ALAD and VDR polymorphisms influenced Hg in blood (β=0.17; 0.37 and 0.17; respectively, p<0.050) while variations on GCLM, GSTT1 and MDR1 (TT) modulated the concentrations of Pb among the subjects (β=-0.14; 0.13 and -0.22; re-spectively, p<0.050). GSTT1 and GCLM polymorphisms also are associated to changes of MDA concentrations. Persons with null GSTM1 genotype had higher activity of the antioxidant enzyme CAT than carries of the allele. Individuals with deletion of both GSTM1 and GSTT1 had a decreased expression of GPx compared to those that expressed at least, one of the enzymes. ALAD 1/2 subjects had lower ALAD activity than individuals with the non-variant genotype. Our findings give further support that polymorphisms related to Hg and Pb metabolism may modulate Hg and Pb body burden and, consequently metals-induced toxicity.

Evaluation of distribution, redox parameters, and genotoxicity in Wistar rats co-exposed to silver and titanium dioxide nanoparticles

ABSTRACT The increasing production of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiO2NPs) has resulted in their elevated concentrations in the environment. This study was, therefore, aimed at determining the distribution, redox parameters, and genotoxic effects in male Wistar rats that were treated with either AgNP or TiO2NP individually, as well as under a co-exposure scenario. Animals were exposed via oral gavage to either sodium citrate buffer (vehicle), 0.5 mg/kg/day TiO2NP, 0.5 mg/kg/day AgNP or a mixture of TiO2NPs and AgNPs. Exposure lasted 45 days after which rats were sacrificed, and tissue biodistribution of Ag and Ti measured. The blood concentration of glutathione (GSH) and activities of glutathione peroxidase (GPx) and catalase (CAT) were determined while the genotoxicity was analyzed using the comet assay in peripheral blood and liver cells. The tissue concentrations of Ag followed the order; blood > liver > kidneys while for Ti the order was kidneys > liver > blood. There was no significant change in the measured redox parameters in animals that were exposed to TiO2NPs. However, there was a significant increase in GSH levels accompanied by a reduction in the GPx activity in AgNP-treated and co-exposed groups. The individual or co-exposure to TiO2NP and AgNP did not markedly induce genotoxicity in blood or liver cells. Data showed that TiO2NP did not produce significant oxidative stress or genotoxicity in rats at the dose used in this study while the same dose level of AgNPs resulted in oxidative stress, but no noticeable adverse genotoxic effects.

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers

Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma–mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.

Toxic and essential elements in Nigerian rice and estimation of dietary intake through rice consumption

In this study, levels and estimated daily intake (EDI) of two toxic elements, Cd and Pb, and eight essential elements: Ca, P, Zn, Mn, Co, Cu, Se and Mo, were determined in Nigerian rice samples. The mean levels of Cd, Pb and Co were 5.43 ± 0.88, 38.66 ± 5.42, 25.8 ± 3.18 ng/g. The mean levels of Ca, P, Zn, Mn, Cu, Se and Mo were 71.5 ± 7.31, 951 ± 52.0, 10.2 ± 0.63, 8.5 ± 0.47, 3.07 ± 0.18, 40.1 ± 9.2 and 0.39 ± 0.05 µg/g, respectively. The percentage contribution to the reference values for each element was 0.54, 7.71, 0.38, 9.51, 8.97, 31.3, 30.7, 5.1 and 60.7% for Cd, Pb, Ca, P, Zn, Mn, Cu, Se and Mo, respectively. The elemental nutrient levels in Nigerian rice samples are comparable to those obtained from other regions and their consumption does not pose any serious health risk to consumers.

Arsenic speciation in rice consumed in south-western Nigeria, and estimation of dietary intake of arsenic species through rice consumption

ABSTRACT This study determined concentrations and speciation of arsenic (As) in rice samples obtained from the cities of Akure, Ore, Ondo and Ikare in Ondo State, south-western Nigeria. The estimated dietary intake of As from rice consumption for total As and the identified As species were compared with the As benchmark dose lower confidence limit. Analyses of rice from the four cities identified three As species: inorganic As, monomethylarsonic, acid and dimethylarsinic acid. Concentrations of total As and the As species differed significantly across the sampling locations (by a factor of 2.5 for total As). Mean levels (±S.D.) were 58.8 ± 0.7 µg/kg total As, 47.0 ± 0.6 µg/kg inorganic As, 0.33 ± 0.03 µg/kg monomethylarsonic acid, and 11.5 ± 0.1 µg/kg dimethylarsinic acid. The estimated mean dietary intakes were 4.1 µg/d total As, 3.3 µg/d inorganic As, 0.02 µg/d monomethylarsonic acid, and 0.8 µg/d dimethylarsinic acid. These values are below the benchmark dose lower confidence limit and comparable to, or lower than, those reported for other countries. Thus, consumption of rice cultivated in south-western Nigeria does not appear to have inherent As-associated health risks.

Metal and Metalloid-Induced Oxidative Damage: Biological Importance of Potential Antioxidants

Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, SP, Brazil Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil Department of Biology, School of Sciences, Federal University of Technology, Akure, Ondo State, Nigeria Kidney Disease Research Collaborative, Translational Research Institute, School of Biomedical Sciences, Faculty of Medicine, NHMRC CKD.QLD CRE, Royal Brisbane and Women’s Hospital, University of Queensland, Brisbane, QLD, Australia

Arsenic, cadmium, and mercury-induced hypertension: mechanisms and epidemiological findings

ABSTRACT Arsenic (As), cadmium (Cd), and mercury (Hg) are toxic elements widely distributed in the environment. Exposure to these elements was attributed to produce several acute and chronic illnesses including hypertension. The aim of this review is to provide a summary of the most frequently proposed mechanisms underlying hypertension associated with As, Cd, and Hg exposure including: oxidative stress, impaired nitric oxide (NO) signaling, modified vascular response to neurotransmitters and disturbed vascular muscle Ca2+ signaling, renal damage, and interference with the renin–angiotensin system. Due to the complexity of the vascular system, a combination rather than a singular mechanism needs to be considered. In addition, epidemiological findings showing the relationship between various biomarkers of metal exposure and hypertension are described. Given the complex etiology of hypertension, further epidemiological studies evaluating the roles of confounding factors such as age, gender, and life style are still necessary.

Chemical Safety of Unpolished Nigerian Rice

Levels of arsenic (As), lead (Pb), cadmium (Cd), calcium (Ca), chromium (Cr), potassium (K), sodium (Na), and zinc (Zn) in locally cultivated rice consumed in Ondo and Ekiti States of Nigeria were investigated. The rice samples were obtained from six different rice-producing towns; Akure, Ondo, Ado, Igbemo, Ikole and Erinjiyan. The estimated dietary intake (EDI) of these elements were determined and compared with the provisional tolerable daily intake (PTDI) and dietary reference intake (DRI) values for toxic and essential elements respectively. The measured mean levels of Pb, As, Cr, Cd, Zn, Na, Ca and K were 0.047 ± 0.007, 0.041 ± 0.004, 0.570 ± 0.032, 0.026 ± 0.003, 7.856 ± 0.659, 42.15 ± 0.191, 337.11 ± 0.315, and 2650.09 ± 0.337 µg/g respectively while the average EDI were 00.101 ± 0.042 µg/day, 0.088 ± 0.14µg/day, 1.234 ± 0.045 µg/day, 0.057 ± 0.002 µg/day, 0.017 ± 0.071 mg/day, 0.091 ± 0.013 mg/day, 0.73 ± 0.018 mg/day and 5.742 ± 0.337 mg/day respectively. The EDIs were not significantly higher than the reference values for the elements except Cr. Also the rice samples were not rich enough in sodium, calcium and potassium compared to the dietary reference intakes for these elements. It is recommended that rice diets should be supplemented with other food items such as meat, fruits and vegetables.