Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity.

Lead is an environmental hazard with great public health concern and has been known to inhibit delta-aminolevulinate dehydratase (ALAD) activity involved in the heme biosynthetic pathway. The study aimed to investigate the influence of ALAD polymorphism (G177C) on retention of Pb-B levels and ALAD activity on occupationally exposed lead workers. In the present study, we enrolled 561 lead exposed and 317 non-occupationally exposed subjects and performed a comprehensive analysis of Pb-B levels along with ALAD activity and genotyping. The frequency of ALAD variants observed in the total subjects (n = 878) was 70.04% for ALAD 1-1, 27.44% for heterozygous ALAD 1-2 and 2.5% for homozygous mutant ALAD 2-2. Our study revealed that ALAD 1-2 carriers presented higher Pb-B levels compared to wild type ALAD 1-1 carriers. Further, a significant difference was observed in the activity of ALAD between ALAD 1-2/ 2-2 and ALAD 1-1 carriers of non-occupationally exposed group indicating that the polymorphic nature of the enzyme may contribute to altered activity of ALAD irrespective of lead exposure. Hence, ALAD 2 allele might contribute to increased susceptibility to high Pb-B retention, and genotyping of ALAD in lead exposed subjects might be used as a prediction marker to impede tissue/organ damage due to lead toxicity.

Diagnosis, evaluation, and treatment of lead poisoning in general population.

Among the heavy metals, lead still remains the major toxic pollutant of the environment. Human exposure to lead can occur through numerous pathways including air, food, dust, soil, and water. In the present study 14 lead poisoned patients with non-occupational lead exposure were evaluated. They were followed up and compared against the controls with no history of lead exposure. The patients had high blood lead levels and symptoms of weakness, dizziness, abdominal pain, generalized body ache, loss of appetite, and anxiety. Repeated course of chelation therapy helped to bring down their body burden of lead. Alternative sources for lead exposure can cause severe lead poisoning in general population. Screening and medical management of such individuals is very important to identify and eliminate sources of lead. The treatment and management requires a thorough medical evaluation and environmental intervention.

Role of essential trace minerals on the absorption of heavy metals with special reference to lead.

Heavy metals are important toxicants known to exert adverse effects in humans and animals, given sufficient exposure and accumulation in the body. This has a great concern both at personal and public health risk. Heavy metals are also known to interact with the essential trace minerals at the level of absorption and also during the metabolism. The adverse effects of the absorbed and accumulated heavy metals include neurological, reproductive, renal and hematological systems. Children are more sensitive than adults to the effects of lead. Efforts are made to understand the mechanism of the interactions of heavy metals with essential trace minerals at the level of absorption. With available sensitive and specific methodologies like Anodic Stripping Voltammetry for the evaluation of the levels of toxic heavy metals such as lead, cadmium, mercury etc., better understanding of heavy metal absorption is made possible.Due to the poor nutritional standards, risk of heavy metal exposure is still a major concern in developing countries. Studies carried out by the author have provided evidence towards the understanding of the prevailing mechanisms of metal-metal interaction at the intestinal level. During growth and development the demand for the essential minerals being at higher level, differentiation of various essential metals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, it is preventable not only with environmental intervention but also by the nutritional management.