cádmio na saúde humana

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Cádmio na saúde humana

http://www.sciencedirect.com/science/issue/7159-2009-997619996-1283057

Historical perspectives on cadmium toxicology

Gunnar F. Nordberga,

aEnvironmental Medicine, Department of Public Health and Clinical Medicine, UmeåUniversity, 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 polishingagent. The first experimental toxicological studies are from 1919. Bone effects andproteinuria in humans were reported in the 1940's. After World War II, a bone diseasewith fractures and severe pain, the itai-itai disease, a form of Cd-induced renalosteomalacia, was identified in Japan. Subsequently, the toxicokinetics andtoxicodynamics of Cd were described including its binding to the proteinmetallothionein. International warnings of health risks from Cd-pollution were issued inthe 1970's. Reproductive and carcinogenic effects were studied at an early stage, but aquantitative assessment of these effects in humans is still subject to considerableuncertainty. The World Health Organization in its International Program on ChemicalSafety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134,

IPCS. WHO, Geneva, 1–280.) identified renal dysfunction as the critical effect and acrude quantitative evaluation was presented. In the 1990's and 2000 severalepidemiological studies have reported adverse health effects, sometimes at lowenvironmental exposures to Cd, in population groups in Japan, China, Europe and USA(reviewed in other contributions to the present volume). The early identification of animportant role of metallothionein in cadmium toxicology formed the basis for recentstudies using biomarkers of susceptibility to development of Cd-related renaldysfunction such as gene expression of metallothionein in peripheral lymphocytes andautoantibodies against metallothionein in blood plasma. Findings in these studiesindicate that very low exposure levels to cadmium may give rise to renal dysfunctionamong sensitive subgroups of human populations such as persons with diabetes.

Keywords: Cadmium and human health; Cadmium toxicokinetics; Cadmiumtoxicodynamics; Historical risk assessment of cadmium exposure; Mechanisms of cadmium toxicity

Current status of cadmium as an environmental health problem

Lars Järupa, b, , and Agneta Åkessonb

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



bInstitute 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 cadmiumintake in the non-smoking population. The bioavailability, retention and toxicity areaffected by several factors including nutritional status such as low iron status. Cadmiumis efficiently retained in the kidney (half-time 10–30 years) and the concentration isproportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidneytubular damage. Cadmium can also cause bone damage, either via a direct effect onbone tissue or indirectly as a result of renal dysfunction. After prolonged and/or highexposure the tubular injury may progress to glomerular damage with decreasedglomerular filtration rate, and eventually to renal failure. Furthermore, recent data alsosuggest increased cancer risks and increased mortality in environmentally exposedpopulations. 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 and3 µg Cd/g creatinine, similar to the points of departure for effects on bone. It can beanticipated that a considerable proportion of the non-smoking adult population hasurinary 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 safetybetween 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 thetolerably daily intake should be set in accordance with recent findings.

Keywords: Cadmium exposure; Kidney effects; Bone effects; Cancer; Epidemiologicalstudies; Risk assessment

Monitoring of human populations for early markers of cadmiumtoxicity: A review

Bruce A. Fowlera,

aDivision of Toxicology and Environmental Medicine, Agency for Toxic Substancesand Disease Registry, Atlanta, GA 30333, USA

Abstract

Exposure of human populations to cadmium (Cd) from air, food and water may produceeffects in organs such as the kidneys, liver, lungs, cardiovascular, immune andreproductive systems. Since Cd has been identified as a human carcinogen, biomarkersfor early detection of susceptibility to cancer are of an importance to public health. Theability to document Cd exposure and uptake of this element through biologicalmonitoring is a first step towards understanding its health effects. Interpretation andapplication of biological monitoring data for predicting human health outcomes requirecorrelation with biological measures of organ system responses to the documentedexposure. Essential to this understanding is the detection and linkage of early biologicalresponses toxic effects in target cell populations. Fortunately, advances in cell biologyhave resulted in the development of pre-clinical biological markers (biomarkers) thatdemonstrate measurable and characteristic molecular changes in organ systems



following chemical exposures that occur prior to the onset of overt clinical disease ordevelopment of cancer. Technical advances have rendered a number of thesebiomarkers practical for monitoring Cd-exposed human populations. Biomarkers will beincreasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-

materials made from combinations of these elements have greatly altered cellular uptakecharacteristics due to particle size. These differences may greatly alter effects at thetarget 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 humanscannot be underestimated due to the rapid expansion of nano-material technologies.This review will attempt to briefly summarize the applications, to date, of biomarkerendpoints for assessing target organ system effects in humans and experimental systemsfrom Cd exposure. Further, it will attempt to provide a prospective look at the possiblefuture of biomarkers. The emphasis will be on the detection of early toxic effects fromexposure to Cd in new products such as nano-materials and identification of populationsat 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, ,

aCenter for Biomedical Research, Population Council, 1230 York Avenue, New York,

NY 10065, USAbSection of Experimental Endocrinology, Department of Pharmacology, UniversidadeFederal de Sao Paulo, Escola Paulista de Medicina, Rua Tres de maio 100, INFAR, VilaClementino, Sao Paulo, SP04044-020, Brazil

Abstract

Cadmium (Cd) is an environmental toxicant and an endocrine disruptor in humans androdents. Several organs (e.g., kidney, liver) are affected by Cd and recent studies haveillustrated 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-basedcompounds (e.g., bisphenols) may account for the recent declining fertility in menamong 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-inducedtoxicity 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) viaspecific signal transduction pathways and signaling molecules, such as p38 mitogen-activated protein kinase (MAPK). We also summarize current studies on factors thatconfer and/or regulate the testis sensitivity to Cd, such as Cd transporters andmetallothioneins, the impact of Cd on the testis as an endocrine disruptor and oxidativestress 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-inducedtesticular 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 preventiveapproaches that can be developed in future studies by blocking or minimizing thedestructive effects of Cd to testicular function in men.

Keywords: Environmental toxicant; Cadmium; Testis; Spermatogenesis; Seminiferousepithelial cycle; Sertoli cells; Germ cells; Blood–testis barrier; Cell adhesion; Infertility;Cancer

Cadmium, diabetes and chronic kidney disease

Joshua R. Edwards , a, and Walter C. Prozialecka

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

Abstract

Recent epidemiological studies suggest a positive association between exposure to theenvironmental pollutant cadmium (Cd) and the incidence and severity of diabetes. Inthis review, we examine the literature suggesting a relationship between Cd exposure,elevated blood glucose levels, and the development of diabetes. In addition we reviewhuman and animal studies indicating that Cd potentiates or exacerbates diabeticnephropathy. We also review the various possible cellular mechanisms by which Cdmay alter blood glucose levels. In addition, we present some novel findings from ourown laboratories showing that Cd elevates fasting blood glucose levels in an animalmodel 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 effectson the pancreas. Together, these findings indicate that Cd may be a factor in thedevelopment of some types of diabetes and they raise the possibility that Cd anddiabetes-related hyperglycemia may act synergistically to damage the kidney.

Keywords: Cadmium; Diabetes; Fasting blood glucose; Insulin; A1

cádmio na saúde humana

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