Lead exposure: a summary of global studies and the need for new studies from Saudi Arabia.

Lead poisoning (plumbism) can cause irreversible genetic and reproductive toxicity, hematological effects, neurological damage, and cardiovascular effects. Despite many efforts to minimize lead poisoning, it continues to be a major health concern in many developing and developed countries. Despite efforts to control lead exposure and toxicity, serious cases of lead poisoning increasingly occur as a result of higher vehicular traffic and industrialization. The biomarkers for identification of genetic susceptibility to a particular disease are useful to identify individuals who are at risk for lead poisoning. Although many such studies have been taken up elsewhere, very few studies were performed in Saudi Arabia to assess susceptibility to lead poisoning. This indicates an urgent need for testing of susceptible individuals. The present paper was planned to understand the genetic susceptibility to lead toxicity in the various population studies conducted worldwide and also to correlate it with the current scenario in Saudi Arabia. Such studies are necessary for appropriate precautions in terms of diet and avoiding exposure to be used in order to prevent adverse health effects.

Effect of sodium fluoride on neuroimmunological parameters, oxidative stress and antioxidative defenses.

AIMS: This study was designed to evaluate the effect of sodium fluoride (NaF) in inducing neuroimmunological, oxidative and antioxidative damage. METHODS: Twenty-four male Wistar rats broadly grouped into four groups containing six rats in each were fed with drinking water containing 20 ppm, 60 ppm, 100 ppm and 0.8 ppm (control) NaF. After 90 days, rats were sacrificed to assess the level of fluoride content and various neurotransmitters in brain. The levels of CD4, natural killer (NK) cells and IgG1 were assessed in blood and spleen. In addition, lipid peroxidation coupled with the levels of various antioxidative enzymes was also recorded. RESULTS: Increase in the NaF concentration resulted in increased fluoride deposition in brain tissue. This increased fluoride content led to increased levels of certain neurotransmitters such as epinephrine, histamine, serotonin and glutamate and decreased levels of norepinephrine, acetylcholine and dopamine in a dose-dependent manner. NaF exposure led to the decrease in the levels of CD4, NK cells and IgG1 coupled with marked increase in lipid peroxidation and impairment of the antioxidative defense system. CONCLUSION: The result of the study emphasizes the toxic role of high NaF doses on the neurological and immunological functions.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Phylogenetic analysis of ALAD and MGP genes related to lead toxicity.

Experimental studies in our laboratory have established the role of delta-aminolevulinic acid dehydratase (ALAD) and matrix gamma-carboxyglutamic acid (MGP) gene polymorphisms in the etiology of lead toxicity. Polymorphisms in these genes influenced the levels of lead in subjects exposed to this metal. In extension to our studies, we aimed to investigate the possible role of these proteins in evolution by studying the phylogenetic relationship and divergence of ALAD and MGP genes using computational phylogenetic methods. The human ALAD and MGP protein sequences from various species were retrieved from Swiss-Prot database and were compared using Basic Local Alignment Search Tool. Multiple sequence alignment was carried out using ClustalW with defaults, and phylogenetic trees for both the genes were built using neighbor-joining method as in Mega software. Our study indicated that ALAD is a highly conserved protein with the same metal binding site distributed in all the phyla (from archaea to chordates). Phylogenetic analysis of MGP gene revealed that it had an important role in the evolution of endogenous skeleton in contrast to exoskeleton of insects. Occurrence of these genes in evolution with conserved metal binding sites strengthens the role of ALAD and MGP genes in regulating heme biosynthesis and mineralization, respectively, in evolution and helps in better understanding of lead poisoning.

A study on the ALAD gene polymorphisms associated with lead exposure.

Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in this gene may affect the response of individuals to lead toxicity symptoms. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on blood lead levels (BLL) and hematological parameters. In all, 113 battery manufacturing unit workers and 102 occupationally unexposed controls from Hyderabad, A.P, India formed the study group. Genotypes for the ALAD G177C polymorphism were determined by Polymerase chain reaction and restriction fragment length digestion. BLL were determined by anode stripping voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture was analyzed using ADVIA cell counter for each sample. The frequencies for ALAD1 and ALAD2 alleles were 0.98 and 0.01, respectively. ALAD 1-2 and ALAD 2-2 genotypes together were considered as a single group and compared with the ALAD 1-1 genotype group. BLL did not differ significantly among ALAD1-1, 1-2, and 2-2 genotypes; however, subjects from the ALAD 1-2/2-2 genotype group showed higher BLL concentrations of 80.51 microg/dL when compared with subjects from the ALAD 1-1 genotype group (50.4 microg/dL). Approximately 29.2% volunteers (nA =A 33) from the occupationally exposed group had hemoglobin levels below 10.0 g/dL. There was no significant difference in total white cell count and platelet count between occupational and non-exposed lead-exposed groups. BLL of occupationally exposed individuals were significantly high compared with the unexposed group. ALAD G177C polymorphism along with BLL and assessment of hematological parameters may play an important role in evaluation and better understanding of the consequences of lead exposure.

Genotoxicity induced by pesticide mixtures: in-vitro studies on human peripheral blood lymphocytes.

To assess the damage caused by pesticides and their mixtures on humans, we designed in-vitro experiments to evaluate their cytotoxicity and genotoxicity. Three equimolar pesticide mixtures were investigated for their capability to affect cultured human peripheral blood lymphocytes. The LC50 values for cytotoxicity, using standard trypan blue dye exclusion and calculated by probit analysis, were 4.18, 5.76, and 7.5 microM for endosulfan, carbofuran, and monocrotophos, respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 0.7, 0.9, and 1.0 microM for monocrotophos + carbofuran, endosulfan + monocrotophos, and endosulfan + carbofuran, respectively, using the method. DNA damage was estimated using chromosomal aberrations (chromatid breaks, fragments, gaps, aneuploidy, and satellite association) and comet assays using 1/10 of the LC50 concentrations. Using a standard alkaline comet assay procedure, high concentrations of individual pesticides (0.5-4.0 microM) caused significant DNA damage as indicated by visible tail lengths. Lower concentrations (0.05-0.5 microM) of their binary mixtures could cause the same effect. The results suggest that analysis of genotoxicity may serve as an important biomarker for occupational and household exposure to pesticides, especially mixtures of pesticides, with different modes of action.