The effects of low environmental cadmium exposure on bone density

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9; 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction (β₂M-U RBP, NAG), glomerular dysfunction (Alb-U and β₂M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.     

Possible effects of environmental cadmium exposure on kidney function in the Japanese general population

Objectives: To examine whether the current level of environmental exposure to cadmium (Cd) is associated with kidney dysfunction among general populations in Japan. Methods: A nationwide survey was conducted in Japan from 1991 to 1997 at 30 survey sites (with no known environmental heavy metal pollution), by the collection of 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples. In practice, 607 non-smoking adult women provided these samples. After being wet-ashed, the samples were analyzed for Cd in food duplicates (Cd-F), in blood (Cd-B) and urine (Cd-U) by inductively-coupled plasma mass spectrometry (ICP-MS). Urine samples were also analyzed for α₁-microglobulin (α₁-MG), β₂-microglobulin (β₂-MG) and retinol-binding protein (RBP), creatinine (cr) and specific gravity. Possible tubular dysfunction in association with Cd exposure was examined by simple, multiple and logistic regression analyses, and comparison among three different Cd-dose groups. To minimize the confounding effects of aging, 367 women from 41 to 60 years old were selected and subjected to the same statistical analyses. Results: The analysis of a whole population of 607 women showed that α₁-MG and possibly β₂-MG increased as a function of Cd-F, Cd-B and Cd-U. When the analysis was repeated with the selected population of 367 women aged 41–60, the Cd dose-dependent changes in α₁-MG and β₂-MG became less evident. The distribution of the selected population with α₁-MG above two low cut-off values of >4.9 and >8.4 mg/g cr or with β₂-MG above the lowest cut-off value of >400 μg/g cr, was biased toward the group with higher Cd-Ucr, but such bias was not significant for both α₁-MG and β₂-MG when higher cut-off values were employed. No bias was detected with RBP. Logistic regression analysis with α₁-MG, β₂-MG and RBP (with cut-off values given above) in combination with age, Cd-F, Cd-B and Cd-Ucr gave essentially the same results. Conclusions: The evidence for kidney dysfunction was of borderline significance in the present study population for which geometric mean Cd-F, Cd-B and Cd-U were 24.7 μg/day, 1.76 μg/l, and 3.94 μg/g cr, respectively. The findings might suggest at the same time that the safety margin is small for the Japanese general population regarding environmental Cd exposure. Received: 26 February 1999 / Accepted: 24 July 1999     

Cadmium in kidney cortex of inhabitants of North-West Germany: its relationship to age,sex, smoking and environmental pollution by cadmium

Summary The cadmium concentration in kidney cortex (CdKc) was determined in 388 deceased persons, who at the time of death had lived in the cities of Düsseldorf and Duisburg, Federal Republic of Germany (FRG), and surrounding areas. The average CdKc concentration was found to be 17.1 g/g wet weight. Individual values range from < 0.4 to 94.3 g/g wet weight. The CdKc levels rapidly increase during the first decades of life. At the age of about 40 years, a plateau phase is reached. At high ages (> 70 years), the CdKc levels tend to decrease. Cigarette smokers have significantly higher CdKc concentrations than non-smokers. The increase of CdKc depends on the number of cigarettes smoked. Cigar and pipe smokers have slightly increased CdKc levels compared to non-smokers. Non-smokers who had spent the major part of their life in the area of Duisburg, a cadmium-polluted area, have, on the average, significantly higher CdKc levels than non-smokers from the less-polluted surrounding areas. In smokers the residential factor is masked by the effect of cigarette smoking.     

House dust as possible route of environmental exposure to cadmium and lead in the adult general population

Contaminated soil particles and food are established routes of exposure. We investigated the relations between biomarkers of exposure to cadmium and lead, and the metal loading rates in house dust in the adult residents of an area with a soil cadmium concentration of > or = 3 mg/kg (n=268) and a reference area (n=205). We determined the metal concentrations in house dust allowed to settle for 3 months in Petri dishes placed in the participants' bedrooms. The continuously distributed vegetable index was the first principal component derived from the metal concentrations in six different vegetables. The biomarkers of exposure (blood cadmium 9.2 vs. 6.2 nmol/L; 24-h urinary cadmium 10.5 vs. 7.0 nmol; blood lead 0.31 vs. 0.24 micromol/L), the loading rates of cadmium and lead in house dust (0.29 vs. 0.12 and 7.52 vs. 3.62 ng/cm(2)/92 days), and the vegetable indexes (0.31 vs. -0.44 and 0.13 vs. -0.29 standardized units) were significantly higher in the contaminated area. A two-fold increase in the metal loading rate in house dust was associated with increases (P<0.001) in blood cadmium (+2.3%), 24-h urinary cadmium (+3.0%), and blood lead (+2.0%), independent of the vegetable index and other covariates. The estimated effect sizes on the biomarkers of internal exposure were three times greater for house dust than vegetables. In conclusion, in the adult population, house dust is potentially an important route of exposure to heavy metals in areas with contaminated soils, and should be incorporated in the assessment of health risks.     

Normal liver function in women in the general Japanese population subjected to environmental exposure to cadmium at various levels

Objectives: Whereas it is well established that environmental exposure to cadmium (Cd) may induce kidney dysfunction, less attention has been paid to the possible disturbance of liver function by Cd exposure. The possibility that liver function is adversely affected by current levels of environmental exposure to Cd as investigated in women in the general population in Japan, where the background level of exposure to Cd is known to be high. Methods: From 1991 to 1997, 24-h food duplicate, peripheral blood and morning spot urine samples were collected from 607 non-smoking and non-habitually drinking women (age range 19–78 years) at 30 survey sites (with no known environmental pollution from heavy metals) throughout Japan. Liver function parameters in serum were examined by conventional methods. After wet-ashing, the food duplicate, blood and urine samples were analyzed for Cd intake via food (Cd-F), Cd in blood (Cd-B), and Cd in urine (Cd-U) by inductively-coupled plasma mass spectrometry. Results: The geometric mean values for Cd-F, Cd-B, and Cd-U were 24.7 (27.1) μg/day, 1.76 (2.07) μg/l, and 3.94 (4.61) μg/g creatinine (values in parentheses for 41- to 60 year-old women), respectively. It as found that the three parameters of ALP, ALT, and AST activity were positively and significantly related to the age of the subjects (whereas no association as detected in cases of γ-GTP, LAP, and albumin). Accordingly, a further analysis as made with 367 women selected by age (41–60 years; about 60% of the total population). Essentially, no Cd dose-dependent changes in liver function parameters were observed in the selected population of this narrower age range. Conclusions: Overall, it seemed prudent to conclude that liver function as not disturbed by the current environmental exposure to Cd in Japan. Received: 16 March 1999 / Accepted: 17 July 1999     

低浓度环境镉暴露对全年龄段人群肾功能的影响

目的旨在确定镉暴露是否与儿童、青少年和成人的早期肾损害生物标志物相关联。方法按分层抽样方法,抽取1 235名调查对象,采集血、尿等生物样本进行检测,并对结果进行流行病学分析。结果男性尿镉的中位数为0.38μg/g肌酐,女性为0.42μg/g肌酐。多元线性回归表明,校正了性别、BMI、血铅和尿肌酐之后,在包含儿童的所有年龄组中,尿镉与肾小管生物标志物(NAG酶和β2微球蛋白)呈正相关,且儿童血镉和肾小管生物标志物呈正相关。结论在包含儿童在内的一般人群中,暴露于低浓度的镉依然会影响肾小管功能。     

环境镉暴露对妊娠结局和胎儿生长发育的影响

目的　评价环境镉暴露对妊娠结局和胎儿生长发育的可能影响。方法　于 2 0 0 2年 11月～ 2 0 0 3年 1月选择湖北省大冶市镉污染地区和对照地区的待产孕妇 ,进行问卷调查和体格检查。同时采集孕妇静脉血、脐带血和胎盘标本测定镉含量。比较镉污染地区和对照地区早产发生率、新生儿窒息发生率、新生儿出生身长和体重差异有无显著性。结果　镉污染地区早产发生率为 2 0 8% ,新生儿窒息发生率为 2 9 2 % ;对照地区分别为 10 0 %和 15 0 % ,两者间差异无显著性。污染地区新生儿出生身长为 ( 4 7 88± 4 15 )cm ,低于对照地区 ( 5 0 65± 2 41)cm (P <0 0 1)。多因素线性回归分析表明 ,脐血镉水平与新生儿出生身长呈显著负相关。结论　环境镉暴露可以显著降低新生儿出生身长。     

镉对去卵巢大鼠肾脏的类雌激素作用

目的观察镉染毒对去卵巢大鼠肾脏中雌激素受体α(ERα)、雌激素受体β(ERβ)表达的影响。方法将24只健康12周龄SPF级SD雌性大鼠随机分为3组,分别为假手术(蒸馏水)组、去卵巢(蒸馏水)组、染镉(200 mg/L)去卵巢组,每组8只。假手术组切除小块卵巢周围的脂肪,去卵巢组和染镉去卵巢组切除双侧卵巢。术后1周,采用自由饮水方式进行染毒,连续染毒12周。采用电感耦合等离子体质谱法测定大鼠血镉、尿镉水平,采用酶联免疫吸附测定血清雌二醇、β2-微球蛋白水平,采用Western blot技术检测肾脏组织中ERα、ERβ蛋白的表达水平。结果与假手术组相比,去卵巢组染镉组12周末体重下降(P0.05)、肾脏系数升高(P0.05),去卵巢组及染镉去卵巢组雌激素水平降低(P0.05);与去卵巢组相比,染镉去卵巢组体重、雌激素水平降低(P0.05),肾脏系数、β2-微球蛋白、尿镉及血镉水平升高(P0.05);染镉去卵巢组血镉与尿镉、β2-微球蛋白、肾脏ERβ的表达水平正相关(P0.05),而与ERα无统计学相关性(P0.05)。结论重金属镉可降低去卵巢大鼠血清雌激素水平及增加雌激素受体β受体表达,这可能是镉的肾毒性作用机制之一。     

Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice

Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 10-30 years in human. To investigate the evolution of cadmium-induced renal effects in the population, a number of 148 residents who lived in cadmium-polluted area were followed-up for 3 years after the reduction of cadmium exposure in rice. Urinary cadmium (UCd), β₂-microglobulin (B2M) and albumin (ALB) were analyzed in 1995 and 1998, respectively. The results demonstrated that the changes of renal effects of residents depended on the levels of UCd before inflow of cadmium to human body declined. In cases where UCd were less than 10 μg/g creatinine in 1995, evidence was found indicating significant decreases in proteinuria (i.e., B2M and ALB) 3 years later, whereas, in cases where the excretion of UCd exceeded 10 μg/g creatinine in 1995, progression was observed. The study of dose-response relationships between UCd and B2M or ALB also showed that the cadmium-induced renal dysfunction might be reversible if UCd concentration was low-level before exposure decreasing, otherwise it might be irreversible or aggravated.     

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of the Federal Republic of Germany

Summary An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic of Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly contaminated by cadmium, lead and other heavy metals, viz. Stolberg and Duisburg. Dusseldorf was selected as a reference area. As a study population we selected 65- and 66-year-old women (n = 286) who had spent the major part of their lives in one of these areas. The average cadmium levels in blood (CdB) and urine (CdU) revealed significant differences in exposure to cadmium in the order Stolberg > Duisburg > Düsseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Düsseldorf groups. However, with respect to the urinary excretion of low molecular weight proteins ( ₂-microglobulin, retinol-binding protein), albuminuria, total proteinuria, aminoaciduria, phosphaturia and some other biological findings, no significant differences between the study populations were noted. Similarly, the prevalence of clinically-confirmed hypertension as well as the relative frequency of hypertensive subjects (systolic 160 and/or diastolic 95 mm Hg) did not differ significantly among the three study groups. There was no exposure-reponse relationship between CdU and tubular proteinuria in the range of the CdU-levels found (0.1 to 5.2 g/g creatinine). However, albuminuria tended to be increased at CdU levels > 2 g/g creatinine.     

Superoxide radical and nephrotoxic effect of cadmium exposure

Pollution and industrial practices result in concentrations of metals and other environmental agents that are related to environmental toxicity. Concentrations of metals are widely related to biochemicals values which are used in disease diagnosis due to environmental toxicity. This work was carried out in order to verify the nephrotoxic effect of cadmium and to clarify the contribution of reactive oxygen species (ROS) in this process. Cadmium chloride was tested for nephrotoxic damage in rats by a single intraperitoneal (i.p.) injection Cd2+ (2 mg/kg) and oral intake (Cd2+ -100mg/l-from CdCl2). The cadmium-induced biochemical alterations included significant increased levels of serum creatinine concentrations, in rats with i.p. injection. Total urinary protein concentrations were only increased in rats with cadmium intake. Lipoperoxide was also increased after 3 and 7 days of the Cd2+ treatment. No changes were observed in glutathione peroxidase activities. Cadmium-induced damage might be due to superoxide radicals (O2-), since Cu-Zn superoxide dismutase activities were decreased by Cd2+ treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in cadmium nephrotoxicity. We concluded that the superoxide radical may be produced as a mediator of nephrotoxic action of cadmium.     

Biological assessment of exposure in factories with second degree usage of cadmium compounds

Summary Biological assessment of occupational exposure to cadmium in five different factories with low-level second degree usage of Cd-compounds has been carried out. In 124 exposed and control male workers the following measurements were performed: cadmium in blood (CdB) and urine (CdU), B₂-microglobulin (B2M), creatinin in urine (Great), hemoglobin (Hb) and hematocrit (Ht). Analysis of 34 pairs of workers matched according to age, smoking habits, ethnic origin and factory, established a significant difference only in CdU, the geometric means being 0.67 g/g Creat in the exposed group and 0.48 g/g Creat in the control group. Significant correlation was found between CdU x age and CdB x smoking habits. Multiple regression analysis showed that for each year increase in age CdU increased 3%, for each percent increase of CdB CdU increased 0.28%; for each cigarette smoked per day CdB increased 1.6%. It is concluded that in this type of work the low external cadmium exposure does not express itself in different CdB-levels, but only in different CdU-levels, indicating an increased body burden due to long term low level occupational cadmium exposure. In biological assessment of exposure to Cd, it is essential to take age and smoking habits fully into account.This study was supported by a grant from the Dutch Prevention Fund and the Ministry of Health and Environmental Protection     

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

Background

Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves.

Objectives

To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors.

Methods

Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated.

Results

The median kidney concentrations were 12.9 μg/g (wet weight) for cadmium, 0.21 μg/g for mercury, and 0.08 μg/g for lead. Kidney Cd increased by 3.9 μg/g for a 10 year increase in age, and by 3.7 μg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 μg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed.

Conclusions

In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.     

The influence of age at exposure to PBBs on birth outcomes

The determination of critical windows of susceptibility to environmental chemical exposures and health has become a major public health focus. This study examined the association between early age at exposure to polybrominated biphenyls (PBBs) and subsequent birth weight and gestational length in offspring among females. The study population consisted of 1111 births that occurred among 560 women enrolled in the Michigan PBB Cohort from 1975 to 1994. Maternal age at exposure was categorized into three groups:<10 years (n = 64), 11-16 years (n = 149), and 17-42 years (n = 347). Overall serum PBB levels ranged from 0 to 1490 ppb, with a median of 2, 3, and 2 ppb in the three age groups, respectively. Separate mixed-effects linear regression models were used to evaluate the effect of age at exposure (years) and initial PBB level (ppb) on birth weight (grams) and gestational age (weeks), controlling for gestational age (weeks) (in the model examining effects on birth weight), BMI (kg/m(2)) and serum PCB level at enrollment (ppb), maternal age and paternal education at delivery, parity, infant gender, interval between the initial serum test and date of delivery (years), and the trimester in which prenatal care was initiated. Relative to the oldest age group, age<10 years at exposure was the most important predictor of increased birth weight (estimated regression coefficient = 225 g, P = 0.012). Infant birth weight increased approximately 16 g for every 10 ppb increase in serum PBBs (P=0.004). There was no association between initial PBB levels and gestational age, nor were initial serum PCB levels associated with either infant birth weight or gestational length. These results provide support for the hypothesis that early age at exposure may be an important determinant in subsequent health effects due to environmental chemical exposures.     

Relationship between environmental exposure to cadmium and bone metabolism in a non-polluted area of Japan

Objectives  

The purpose of this study was to investigate the effects of environmental low-grade cadmium exposure on bone in the population of a non-polluted area. We investigated the relationship between environmental cadmium exposure (via rice intake) and bone metabolism in middle-aged and elderly women living in a non-polluted area in Japan.     

镉对肠道功能影响的研究进展

目的 综述镉肠道毒性及其毒作用机制,为镉的肠道毒性与人体疾病关系的研究提供理论依据。方法 以“镉”、“肠道”、“微生物”、“益生菌”作为CNKI数据库、维普数据库和万方数据库检索词,以“Cadmium”、“Cd”、“Gut”、“Gastrointestinal Microbiome”、“Intestine”、“Bowel”、“Microorganism”作为PubMed数据库的检索词,参考文献56篇。结果 镉对肠道功能的毒性影响有两个方面:一方面镉影响肠道生理功能和结构,导致肠壁细胞通透性增加和组织结构破坏;另一方面镉引起肠道微生物数量和菌群多样性的改变、脂多糖产生增加和屏障功能受损,从而导致机体内毒素血症和全身炎症。结论 镉对肠道功能的毒性作用与人体健康和疾病的发生、发展密切相关,未来还需要更深入的研究去阐释镉对肠道功能影响的作用机制。     

亚慢性镉暴露BALB/c小鼠丝裂原活化蛋白激酶信号通路蛋白在肾损伤中的作用

目的 探讨丝裂原活化蛋白激酶（mitogen activated protein kinase,MAPK）和细胞外信号调节激酶（extracellular signal-regulated kinases,ERK）在亚慢性镉染毒小鼠肾脏损害发生后表达的变化及其意义。方法 21只雌性BALB/c小鼠随机分成3组,高、低剂量染镉组分别腹腔注射CdCl2溶液10.0、2.5 μmol/kg,对照组腹腔注射等量生理盐水,每周3次连续染毒14周。对肾脏进行苏木精-伊红(HE)染色、碘酸雪夫(PAS)染色和胶原纤维染色（Masson染色）,观察肾组织病理变化;免疫印迹(Western blot)法检测肾脏中ERK、p38、c-Jun氨基末端激酶(JNK)蛋白及其磷酸化蛋白的表达差异。结果 高剂量染镉组pERK、pp38和pJNK蛋白表达水平均高于对照组,差异有统计学意义(P＜0.05),低剂量染镉组pJNK蛋白表达水平高于对照组,差异有统计学意义（P＜0.05）。镉染毒组的bcl-2、bax蛋白表达水平降低,且bcl-2/bax比值低于对照组,差异有统计学意义(P＜0.05)。镉染毒组肾小球和肾小管均有损害。结论 CdCl2可能通过调节ERK、JNK和p38蛋白激酶信号相关蛋白表达水平的变化,引发肾脏损害。     

Differential protein expression of kidney tissue in the scallop Patinopecten yessoensis under acute cadmium stress

Morphological and proteomic changes in the kidney of scallops exposed to acute cadmium chloride (CdCl₂) were observed, analyzed and compared with those in the non-exposed control group. Under microscopy the paraffin-embedded sections of the kidney revealed that the microstructure of the tissue had been severely deformed after Cd exposure. Two dimensional electrophoresis, MALDI-TOF mass spectrometry and database searches showed 13 differentially expressed protein spots, of which 11 were up-regulated, while two were down-regulated. Among these proteins, guanylate kinase (GK) and C₂H₂-type zinc finger protein are considered to be tightly connected with Cd toxicity. Further studies using quantitative PCR method validated that the GK mRNA was induced under Cd stress. Other proteins identified which had some relevance to Cd toxicity are also discussed. We suggested that differential proteins such as GK could play a potential role as novel biomarkers for monitoring the level of Cd contamination in seawater.     

Longitudinal studies on the health effects of exposure to environmental cadmium

Renal damage induced by cadmium (Cd) results in a proximal renal tubular dysfunction, characterized by low-molecular weight (LMW) proteinuria, renal glucosuria, generalized aminoaciduria and decreased renal tubular reabsorption of uric acid and phosphate. Since LMW proteinuria is thought to be one of the earliest adverse health effects caused by Cd, the prevention of the progress of LMW proteinuria is important to avoid further deteriorations in the health condition. Follow-up studies on residents in Cd-polluted areas and Cd-exposed workers have indicated that Cd-induced LMW proteinuria is generally irreversible and progressive even after the cessation or reduction of exposure. The intensity of exposure and the body burden of Cd before the reduction of exposure may influence the prognosis of Cd-induced LMW proteinuria. Several studies have reported a gradual decline in the glomerular filtration rate even after the reduction of Cd exposure. Cohort studies performed in Cd-polluted areas of Japan showed that renal tubular dysfunction and a decreased glomerular filtration rate were strongly associated with increased risk of mortality. However, the results also suggested that overall mortality rates in Cd-polluted areas were not necessarily increased, because of the low mortality among those with urinary beta 2-microglobulin concentrations < 1,000 micrograms/g creatinine. At present, incidence data are too limited to draw a conclusion regarding the cancer risk among residents in Cd-polluted areas.     

镉对大鼠胰脏的毒作用

目的探讨镉对内分泌和外分泌功能的影响。方法将96只SD大鼠分为4组,分别为对照组和50、100、200mg/LCdCl2染毒组,饮水染毒30、60、90d。测定不同染毒时间大鼠血糖、尿糖、血胰岛素、淀粉酶的改变及血液中金属含量的改变;测定尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG);并测定了胰脏组织中金属的含量以及胰脏金属硫蛋白基因、胰岛素基因和淀粉酶基因的表达情况。结果染毒组大鼠血糖水平在染毒90d的中、高剂量组有明显增加,差异有统计学意义(P<0.05),中剂量组血糖平均值为5.83mmol/L,高剂量组为6.46mmol/L;发现尿糖水平的增高先于尿NAG的增高。各剂量组大鼠血液和胰脏中镉的含量明显增加。在染毒90d中、高剂量组血锌含量降低。在染毒30d的中、高剂量组血液中胰岛素水平明显降低,而血淀粉酶改变不明显。在染毒90d的中、高剂量组胰脏组织中锌的含量明显增加。胰脏中金属硫蛋白基因表达均有不同程度的增加;胰岛素基因的表达除染毒60d中剂量组明显降低外,其他各组差异均无统计学意义(P>0.05)。而胰淀粉酶的基因表达在染毒60d和90d的中、高剂量组均明显增高。结论镉可以在胰脏组织蓄积,引起组织中必需元素锌水平的改变,导致基因和蛋白表达的改变,进一步引起胰脏内、外分泌功能的改变。