Cádmio Na Saúde Humana

Cádmio na saúde humana http://www.sciencedirect.com/science/issue/7159-2009-997619996-1283057

Historical perspectives on cadmium toxicology Gunnar F. Nordberga, a

Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, SE-90187 Umeå, Sweden

Abstract The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1–280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes. Keywords: Cadmium and human health; Cadmium toxicokinetics; Cadmium toxicodynamics; Historical risk assessment of cadmium exposure; Mechanisms of cadmium toxicity

Current status of cadmium as an environmental health problem Lars Järupa, b, a

,

and Agneta Åkessonb

Department of Epidemiology and Public Health, Imperial College London, UK

b

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10–30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose–response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 µg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 µg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings. Keywords: Cadmium exposure; Kidney effects; Bone effects; Cancer; Epidemiological studies; Risk assessment

Monitoring of human populations for early markers of cadmium toxicity: A review Bruce A. Fowlera, a

Division of Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Atlanta, GA 30333, USA

Abstract Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems

following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cdbased high technology materials. For example, cadmium-selenium (CdSe), nanomaterials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in humans and experimental systems from Cd exposure. Further, it will attempt to provide a prospective look at the possible future of biomarkers. The emphasis will be on the detection of early toxic effects from exposure to Cd in new products such as nano-materials and identification of populations at special risk for Cd toxicity. Keywords: Cadmium; Biomarkers; Kidney; Liver; Lung; Cardiovascular; Immune; Reproductive organs; Cadmium Nanomaterials

Cadmium-induced testicular injury Erica R. Siua, Dolores D. Mruka, Catarina S. Portob and C. Yan Chenga,

,

a

Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065, USA b

Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Rua Tres de maio 100, INFAR, Vila Clementino, Sao Paulo, SP04044-020, Brazil

Abstract Cadmium (Cd) is an environmental toxicant and an endocrine disruptor in humans and rodents. Several organs (e.g., kidney, liver) are affected by Cd and recent studies have illustrated that the testis is exceedingly sensitive to Cd toxicity. More important, Cd and other toxicants, such as heavy metals (e.g., lead, mercury) and estrogenic-based compounds (e.g., bisphenols) may account for the recent declining fertility in men among developed countries by reducing sperm count and testis function. In this review, we critically discuss recent data in the field that have demonstrated the Cd-induced toxicity to the testis is probably the result of interactions of a complex network of causes. This is likely to involve the disruption of the blood–testis barrier (BTB) via specific signal transduction pathways and signaling molecules, such as p38 mitogenactivated protein kinase (MAPK). We also summarize current studies on factors that confer and/or regulate the testis sensitivity to Cd, such as Cd transporters and metallothioneins, the impact of Cd on the testis as an endocrine disruptor and oxidative stress inducer, and how it may disrupt the Zn2+ and/or Ca2+ mediated cellular events. While much work is needed before a unified mechanistic pathway of Cd-induced testicular toxicity emerges, recent studies have helped to identify some of the likely

mechanisms and/or events that take place during Cd-induced testis injury. Furthermore, some of the recent studies have shed lights on potential therapeutic or preventive approaches that can be developed in future studies by blocking or minimizing the destructive effects of Cd to testicular function in men. Keywords: Environmental toxicant; Cadmium; Testis; Spermatogenesis; Seminiferous epithelial cycle; Sertoli cells; Germ cells; Blood–testis barrier; Cell adhesion; Infertility; Cancer

Cadmium, diabetes and chronic kidney disease Joshua R. Edwards a

, a,

and Walter C. Prozialecka

Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA

Abstract Recent epidemiological studies suggest a positive association between exposure to the environmental pollutant cadmium (Cd) and the incidence and severity of diabetes. In this review, we examine the literature suggesting a relationship between Cd exposure, elevated blood glucose levels, and the development of diabetes. In addition we review human and animal studies indicating that Cd potentiates or exacerbates diabetic nephropathy. We also review the various possible cellular mechanisms by which Cd may alter blood glucose levels. In addition, we present some novel findings from our own laboratories showing that Cd elevates fasting blood glucose levels in an animal model of subchronic Cd exposure before overt signs of renal dysfunction are evident. These studies also show that Cd reduces insulin levels and has direct cytotoxic effects on the pancreas. Together, these findings indicate that Cd may be a factor in the development of some types of diabetes and they raise the possibility that Cd and diabetes-related hyperglycemia may act synergistically to damage the kidney. Keywords: Cadmium; Diabetes; Fasting blood glucose; Insulin; A1