汞在大鼠肾和尿中的分布及其与蛋白结合规律的研究

本研究用1mg/kg HgCl_2(SC)多次染毒,复制大鼠亚急性中毒模型,测定了汞在大鼠肾脏亚细胞中的分布。用Sephadex G-75凝胶层析分析汞与肾胞浆蛋白的结合状况和大鼠尿中汞的排泄形式,并对尿蛋白进行了SDS-PAGE电泳图谱分析。从生化毒理学角度探讨了汞引起肾脏慢性损伤时,汞与蛋白的结合状况和尿蛋白变化的规律及其床临诊断价值。     

D-青霉胺和二巯丙磺酸钠对汞致大鼠肾毒性的影响

目的　研究预投D- 青霉胺 (D- penicillamine ,DPA)和二巯丙磺酸钠 (2 ,3 - Dimercato 1 Propanesulfonate ,DMPS)对汞致急性肾毒性的保护作用及其机制。方法　 48只Wistar大鼠随机分成 6组。第 1组以 5mL/kg体重皮下注射质量分数为 0 . 9%的氯化钠溶液 ,第 2、3和 4组分别皮下注射 0 .75、1.5和 2 .5mg kgHgCl2 溶液。第 5、6组大鼠分别腹腔注射2 0 0 μmoLDMPS和 2 0 0 μmoLDPA ,2h后再投与 2 5mg/kgHgCl2 溶液。染毒 12h后 ,收集 12h尿样 ,测定尿N- 乙酰 - β- D- 氨基葡萄糖苷酶 (NAG)和尿碱性磷酸酶 (ALP)活力、尿蛋白和尿汞含量。染毒 48h后 ,切取肾脏和肝脏 ,分别测定肾脏和肝脏中的丙二醛 (MDA)和谷胱甘肽 (GSH)含量、谷胱甘肽过氧化物酶 (GSH- Px)活力、肝脏汞和肾脏汞含量。结果　DMPS显著降低NAG和ALP活力和尿蛋白含量 ;DPA明显降低NAG活力和尿蛋白含量 ,对ALP没有影响。DMPS显著降低肾脏MDA含量 ,而DPA对肾脏MDA含量没有影响。DMPS-和DPA两干预组在肾脏中GSH含量和GSH -Px活力都明显高于 2 . 5mg kg染汞组 ,差异有显著性。DPA能显著降低肾脏汞含量。结论　DMPS比DPA更能有效地保护肾功能。DMPS会显著减轻汞在肾脏的氧化损伤 ,而DPA则没有影响。DMPS和DPA能明显减少肾脏GSH和GSH- Px的耗     

口腔科医务人员尿汞检测分析

目的评价汞对口腔科专业医护人员的危害情况以及劳动防护的效果。方法 1991年-2011年,每4年对口腔内科在职医师进行尿汞检测,按工龄分为<5年组、5-9年组、10-14年组及≥15年组,并进行统计分析。结果尿汞值呈逐年下降趋势(P<0.05);1991年度-2003年度,各工龄组之间尿汞水平差异无统计学意义(P>0.05);2007年度及2011年度,工龄短的医务人员尿汞水平显著低于工龄长的医务人员(P<0.05)。结论加强劳动防护及新型环保材料的推广应用,可明显减少口腔科医务人员工作环境中的汞接触。     

汞合金对成年填充患者肾功能的影响

目的分析牙科汞合金对成年充填患者肾功能的影响.方法128名牙科汞合金充填者与128名对照作为研究对象.测定尿中汞、白蛋白(ALB)、β2微球蛋白尿(β2-MG)和N-已酰-β-D-氨基葡萄糖苷酶(NAG)水平,并用尿肌酐进行校正.结果充填组的平均尿汞水平为0.434nmolHg/mmolCr,显著高于对照组的平均水平(0.357nmolHg/mmolCr,P=0.000).汞合金充填面数量、喜烫食习惯、磨牙习惯以及性别是影响汞释放的主要因素.充填组与对照组间尿ALB没有统计学差异.虽然45岁以上充填者β2-MG和NAG高于对照,但均在正常范围之内.结论虽然牙科汞暴露可以增加机体汞负荷,但本研究表明目前的暴露水平下还不会导致明显的肾脏损害.     

低剂量无机汞宫内及哺乳期暴露对仔大鼠肝、肾和脑组织中谷胱甘肽抗氧化物酶系统的影响

目的　研究低剂量无机汞子宫内及哺乳期暴露对仔大鼠肝脏、肾脏及脑组织中谷胱甘肽抗氧化物酶系统的影响 ,探讨低剂量无机汞对子代发育潜在的毒性。方法　对怀孕d 0的母大鼠进行 0 .2mg·L- 1Hg2 +饮水染毒直至仔鼠出生后d 2 0断乳期。研究仔鼠肝脏、肾脏及脑区 (大脑、小脑、脑干、海马及其余脑组织 )中汞的分布及汞暴露对上述组织中总巯基含量、还原型谷胱甘肽 (GSH)水平及谷胱甘肽过氧化物酶 (GSH Px)活性的影响。结果汞暴露后仔鼠肾脏中汞的含量最高 ,其次是肝脏和脑组织。在所研究的仔鼠各脑区中 ,海马汞含量最高 ,其次是小脑和大脑。汞暴露组仔鼠肝脏和肾脏中巯基含量比对照组升高了 2倍 ,而脑区中汞暴露组巯基含量与对照组相比则降低至 1/ 2～ 1/ 3。汞暴露组仔鼠肝脏中GSH水平与对照组相比升高了6 5 % ,而在肾脏和脑组织中GSH的水平与对照组相比则显著降低 ,其中 ,汞暴露组仔鼠各脑区中GSH水平降低幅度与对照组相比均超过了 5 8%。除肝脏外 ,汞暴露组仔鼠肾脏和脑区中GSH Px活性明显下降。在脑组织中 ,除海马外 ,GSH Px活性在汞暴露组其他 4个脑区中的下降幅度均超过 80 %。结论　低剂量无机汞子宫内及哺乳期暴露对仔鼠肾脏 ,特别是对脑组织的正常发育造成了一定程度的危害 ;但上述指标对肝脏的     

松花粉对急性汞中毒大鼠肝肾的保护作用及机制研究

目的研究松花粉对急性汞中毒大鼠肝肾的保护作用及机制。方法将大鼠随机均分为正常对照组,染汞模型组,松花粉低、中、高剂量组(2、4、8 g/kg)。通过皮下注射HgCl_2建立急性汞中毒模型,末次染汞后,各组分别灌胃给予相应药物,2次/d,共5 d。通过电感耦合等离子体质谱仪,测定肝汞、肾汞、血汞和尿汞的含量。通过试剂盒,测定尿素氮(BUN)、尿蛋白、尿乳酸脱氢酶(LDH)、尿碱性磷酸酶(ALP),血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL),以及肝、肾中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)和丙二醛(MDA)的含量或活性。结果与正常对照组比较,染汞模型组大鼠的肝汞、肾汞、血汞、尿汞、BUN、尿蛋白、尿LDH、尿ALP、血清ALT、血清AST、血清TBIL、肾脏MDA和肝脏MDA含量或活性均升高(P<0.01),肾脏和肝脏SOD、GSH-Px、GSH含量或活性降低(P<0.01)。与染汞模型组比较,松花粉低、中、高剂量组大鼠的尿汞含量增加(P<0.05或P<0.01),上述其余指标均能显著地向正常对照组的数值变化(P<0.05或P<0.01)。结论松花粉具有清除体内汞蓄积、修复急性汞中毒诱导的急性肝肾损伤的作用,其机制与抑制脂质过氧化损伤相关。     

沙棘油和亚硒酸钠对汞诱导的大鼠肝肾氧化损伤的影响

目的通过汞诱导大鼠肝肾氧化损伤,观察沙棘油(Sea Buckthorn Oil,SBO)和亚硒酸钠(Na2SeO3)干预效应。方法Wister大鼠随机分成对照组、单纯染汞组、SBO和Na2SeO3处理组。测定肝、肾及尿中汞含量,肝、肾中GSH、MDA、蛋白含量和SOD、GSH-PX活力。结果与单纯染汞组相比,SBO处理组尿汞含量增加(P<0.05),肝GSH-PX活力升高(P<0.01);Na2SeO3处理组肝汞增加,肾和尿汞含量下降,肝GSH-PX活力、GSH含量均升高(P<0.01),肝SOD活力和肾GSH-PX活力均增加(P<0.05),肾MDA含量下降(P<0.05)。结论沙棘油具有促进汞从肾脏排出的作用,对汞诱导的肝氧化损伤具有一定保护作用,对肾氧化损伤未表现出明显的保护作用。Na2SeO3可有效拮抗汞诱导的肝肾氧化损伤作用。     

实验室汞污染引起慢性轻度汞中毒1例报道

实验室汞污染引起的慢性轻度汞中毒,患者临床上出现头痛、头晕、全身乏力、手抖、睡眠欠佳、性格改变等症状,并有口腔溃疡、手颤(+)、尿汞增高,经驱汞治疗后症状减轻,诊断慢性轻度汞中毒。     

仪器测量尿汞的方法学评价

汞及其化合物作为一种常用工业金属材料具有广泛的使用范围,汞在常温条件下即能蒸发,其蒸汽易经呼吸道进入人体产生毒性作用,主要通过肾脏由尿液排泄。因此,尿液中汞含量测定结果,是诊断职业性汞中毒重要的生物学评价指标。我单位采用酸性氯化亚锡还原法[1],检测前需加酸消解样品后用冷原子吸收测汞仪测定;而DMA-80直接测汞仪,目前还没有该仪器测定尿汞的国家卫生行业标准方法。两种仪器的测定结果有无差异未见文献报道。本研     

姜黄素对汞致大鼠肾损伤保护作用的实验研究

目的探讨姜黄素对汞致大鼠肾损伤的影响,为汞中毒的发病机制和防治提供实验依据。方法 Wistar大鼠30只按体重随机分为5组,每组6只,雌雄各半。分别为对照组、低剂量染汞组、中剂量染汞组、高剂量染汞组和姜黄素预处理组。1~4组大鼠予皮下注射0.9%氯化钠溶液,第5组大鼠给予皮下注射100 mg/kg姜黄素;2 h后,第1组腹腔注射生理盐水,第2~5组大鼠分别腹腔注射2.2、4.4、8.8和8.8μmol/kg氯化汞溶液,连续干预与染毒3 d。第3天染毒2 h后将动物放入代谢笼,收集24 h尿液测定尿汞和尿蛋白含量,以及尿碱性磷酸酶(ALP)、β-N-乙酰氨基葡萄糖苷酶(NAG)和乳酸脱氢酶(LDH)活力;用乙醚将大鼠麻醉,腹主动脉采血测定血清尿素氮(BUN);切取肾皮质,测定肾皮质汞、还原型谷胱甘肽(GSH)和丙二醛(MDA)的含量及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力。结果与对照组比较,随着染汞剂量的增加,肾皮质汞、尿汞、尿蛋白和BUN含量均升高;尿NAG、LDH和ALP活力均升高;肾皮质GSH和MDA含量明显升高而GSH-Px和SOD活力显著下降,差异具有统计学意义(P0.05)。姜黄素预处理组与高剂量氯化汞染毒组比较,各项指标均有不同程度的改善,差异有统计学意义(P0.05)。结论姜黄素对汞致大鼠肾损伤具有一定的保护作用。     

Quantitative evaluation of urinary porphyrins as a measure of kidney mercury content and mercury body burden during prolonged methylmercury exposure in rats.

Changes in urinary porphyrin excretion patterns (porphyrin profiles) during prolonged mercury exposure are attributable to mercury accumulation in the kidney and to consequent effects of Hg2+ on renal porphyrin metabolism. In the present study, we evaluated the quantitative relationship of urinary porphyrin concentrations to mobilizable renal mercury content, using the metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS) to modulate kidney mercury levels. Rats exposed to methylmercury hydroxide (MMH) at 10 ppm in drinking water for 6 weeks were treated with up to 3 consecutive doses of DMPS (100mg/kg, ip) at 72-h intervals. Consistent with previous findings, the concentrations of pentacarboxyl- (5-) and copro- (4-) porphyrins and of an atypical porphyrin specific to mercury exposure, precoproporphyrin, were significantly elevated in urine of MMH-exposed rats, compared with that of rats exposed to distilled water (dH2O) for the same period. Consecutive DMPS treatments of MMH-exposed rats significantly decreased kidney concentrations of total, as well as Hg2+ and CH3Hg+ species, and promoted increased urinary mercury excretion. Concomitantly, DMPS treatment decreased both kidney and urinary porphyrin concentrations, consistent with depletion of renal mercury levels. Regression analyses demonstrated a high correlation (r approximately 0.9) between prechelation urinary porphyrins and postchelation urinary mercury levels and also between prechelation urinary porphyrins and prechelation kidney mercury concentrations. These findings demonstrate that urinary porphyrin concentrations relate quantitatively to DMPS-mobilizable mercury in the kidney and, therefore, serve as a biochemical measure of renal mercury content.     

Sex and age differences in mercury distribution and excretion in methylmercury-administered mice

Sex differences in mercury distribution and excretion after single administration of methylmercury chloride (MMC, 5 mg/kg) were studied in mice. A sex difference in urinary mercury excretion was found in sexually mature mice (age of 7 wk) of C57BL/6N and BALB/cA strains. Males showed higher mercury levels in urine than females, though no significant difference was found in fecal mercury levels 24 h post exposure to MMC. The higher urinary excretion rates in males accounted for significant lowering of mercury levels in the brain, liver, and blood, but not in the kidney, which showed higher values. At 5 min, however, these sex difference was found only in the kidney, showing higher levels in males. Changes in mercury distribution with time were studied in C57BL/6N mice. The brain mercury increased in both sexes up to 3 d, and decreased only in males on d 5. Liver and blood mercury decreased with time in both sexes, and these were constantly higher in females than in males. Renal mercury in males decreased to similar levels to females on d 3. The sex differences at various ages were studied with C57BL/6N mice 24 h after dosing. Two-week-old mice, the youngest in this study, did not show significant sex difference in the mercury distribution and excretion, and their urinary mercury levels were much lower as compared to the older mice. Then, urinary mercury excretion in both sexes increased at 4 wk of age and then decreased at 45 wk of age. At 4, 7, 10, and 45 wk of age, males showed higher urinary mercury levels than females. These studies demonstrated sex and age differences in the mercury distribution and urinary excretion after methylmercury administration in mice. From these findings, it has been suggested that urinary mercury excretion may be related to sex hormones, especially androgens.     

A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. II. Application and validation of the model in humans

The objective of this study was to develop a biologically based dynamical model describing the disposition kinetics of methyl mercury and its inorganic mercury metabolites in humans following different methyl mercury exposure scenarios. The model conceptual and functional representation was similar to that used for rats but relevant data on humans served to determine the critical parameters of the kinetic behavior. It was found that the metabolic rate of methyl mercury was on average 3 to 3.5 times slower in humans than in rats. Also, excretion rates of organic mercury from the whole body into feces and hair were 100 and 40 times smaller in humans, respectively, and urinary excretion of organic mercury in humans was found to be negligible. The human transfer rate of inorganic mercury from blood to hair was found to be 5 times lower than that of rats. On the other hand, retention of inorganic mercury in the kidney appeared more important in humans than in rats: the transfer rate of inorganic mercury from blood to kidney was 19 times higher than in rats and that from kidney to blood 19 times smaller. The excretion rate of inorganic mercury from the kidney to urine in humans was found to be twice that of rats. With these model parameters, simulations accurately predicted human kinetic data available in the published literature for different exposure scenarios. The model relates quantitatively mercury species in biological matrices (blood, hair, and urine) to the absorbed dose and tissue burden at any point in time. Thus, accessible measurements on these matrices allow inferences of past, present, and future burdens. This could prove to be a useful tool in assessing the health risks associated with various circumstances of methyl mercury exposure.     

Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium.

Sensitive biomarkers are needed to detect kidney injury at the earliest stages. The objective of this study was to determine whether the appearance of kidney injury molecule-1 (Kim-1) protein ectodomain in urine and kidney injury molecule-1/hepatitis A viral cellular receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be more predictive of renal injury after exposure to nephrotoxicants when compared to traditionally used biomarkers. Male Sprague-Dawley rats were injected with a range of doses of gentamicin, mercury (Hg; HgCl2), or chromium (Cr; K2Cr2O7). The results showed that increases in urinary Kim-1 and kidney Kim-1/Havcr1 gene expression paralleled the degree of severity of renal histopathology and were detected at lower doses of nephrotoxicants when compared to blood urea nitrogen (BUN), serum creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG). In a time course study, urinary Kim-1 was elevated within 24 h after exposure to gentamicin (100 mg/kg), Hg (0.25 mg/kg), or Cr (5 mg/kg) and remained elevated through 72 h. NAG responses were nephrotoxicant dependent with elevations occurring early (gentamicin), late (Cr), or no change (Hg). At 72 h, after treatment with any of the three nephrotoxicants, there was increased Kim-1 immunoreactivity and necrosis involving approximately 50% of the proximal tubules; however, only urinary Kim-1 was significantly increased, while BUN, serum creatinine, and NAG were not different from controls. In rats treated with the hepatotoxicant galactosamine (1.1 mg/kg), serum alanine aminotransferase was increased, but no increase in urinary Kim-1 was observed. Urinary Kim-1 and kidney Kim-1/Havcr1 expression appear to be sensitive and tissue-specific biomarkers that will improve detection of early acute kidney injury following exposure to nephrotoxic chemicals and drugs.     

Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on tissue and urine mercury levels following prolonged methylmercury exposure in rats.

Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to reduce brain, kidney, and blood Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg2+) and organic (CH3Hg+) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS). Following MMH treatment for 9 weeks, Hg2+ and CH3Hg+ concentrations were 0.28 and 4.80 microg/g in the brain and 51.5 and 42.2 microg/g in the kidney, respectively. Twenty-four hours after ip administration of a single DMPS injection (100 mg/kg), kidney Hg2+ and CH3Hg+ declined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH3Hg+ fraction. Concomitantly, Hg2+ and CH3Hg+ in urine increased by 7.2- and 28.3-fold, respectively, compared with prechelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMPS injections (100 mg/kg) given at 72-h intervals significantly decreased total mercury concentrations in kidney, brain, and blood. However, the decrease in brain and blood mercury content was restricted entirely to the CH3Hg+ fraction, consistent with the slow dealkylation rate of MMH in these tissues. Mass balance calculations showed that the total amount of mercury excreted in the urine following successive DMPS injections corresponds quantitatively to the total amount of mercury removed from the kidney, brain, and blood of MMH-exposed rats. These findings confirm the efficacy of consecutive DMPS treatments in decreasing mercury concentrations in target tissue and in reducing overall mercury body burden. They demonstrate further that the capacity of DMPS to deplete tissue Hg2+ is highly tissue-specific and reflects the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg2+ levels in brain or blood may explain the inefficacy of DMPS and similar chelating agents in the remediation of neurotoxicity associated with prolonged MMH exposure.     

Urinary porphyrin profiles as biomarkers of trace metal exposure and toxicity: Studies on urinary porphyrin excretion patterns in rats during prolonged exposure to methyl mercury

Studies were conducted to define the specific changes in the urinary porphyrin excretion pattern (porphyrin profile) and the time course of those changes in rats exposed to mercury as methyl mercury hydroxide (MMH) at 5 or 10 ppm in the drinking water for up to 30 weeks. The urinary porphyrin profile elicited by MMH is uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins, and of a third atypical porphyrin with as yet undetermined chemical characteristics. Changes in the porphyrin profile were observed as early as 1 or 2 weeks following initiation of exposure to MMH at 10 or 5 ppm, respectively, and were sustained as long as 40 weeks following cessation of MMH treatment. The magnitude of the urinary porphyrin profile at either MMH dose level increased progressively during the course of mercury treatment and was highly correlated with the renal mercury concentration. A subsequent decline in the magnitude of the urinary porphyrin profile in animals exposed to 10 ppm MMH for more than 10 weeks was associated with the accumulation of high levels of Hg2+ in kidney cells and loss of renal functional status. These findings demonstrate that mercury elicits a unique change in the urinary porphyrin excretion pattern which is related to the dose and duration of mercury treatment. The association of urinary porphyrin excretion rates with renal mercury content and functional status suggests that urinary porphyrin profiles may serve as a useful biomarker of mercury accumulation and nephrotoxicity during prolonged mercury exposure.     

Higher faecal excretion and lower tissue accumulation of mercury in Wistar rats from contaminated fish than from methylmercury chloride added to fish.

A short-term low level exposure experiment was conducted on rats in order to determine urinary and faecal excretion, accumulation, and biological responses to methylmercury from fish products. Male Wistar rats were fed fish-meal diets containing methylmercury contaminated fish (1.45 or 2.61 mgHg/kg as methylmercury), uncontaminated fish supplemented with methylmercury chloride (CH3HgCl) at similar levels (1.24 and 2.49 mgHg/kg, respectively) or uncontaminated fish as a control (0.052 mgHg/kg) for 4 weeks (n=6 rats per treatment). After 2 and 4 weeks of exposure, rats were placed in metabolic chambers for 48 h to assess overall faecal and urinary excretion of mercury. The overall faecal excretion in rats fed fish supplemented with CH3HgCl (12%) was significantly lower (P <0.05) than rats fed methylmercury in fish muscle (19%) or rats fed control diet (76%). Urinary excretion did not differ among the experimental groups. Rats fed the highest level of CH3HgCl had a significantly higher (P <0.05) blood, liver, kidney and brain mercury contamination compared to rats fed methylmercury contaminated fish or rats fed control diet. Metallothionein levels in kidney were significantly higher in CH3HgCl-fed rats compared to rats fed contaminated fish. The results indicate a higher faecal excretion and lower tissue accumulation, and metallothionein induction in rats following exposure to methylmercury naturally incorporated in fish compared to methylmercury chloride added to the same matrix.     

Methoxyethyl Mercury Toxicity in Pigs: Kidney Function and Mercury Distribution

Abstract Female pigs were fed methoxyethyl mercury-contaminated feed at two levels: 11 and 44 mg Hg per kg feed, corresponding to a daily dose of 0.45 and 1.80 mg Hg per kg b.wt. The pigs on the lower dose level were exposed for 12 weeks without any obvious signs of toxicity, while the pigs on the higher dose level died after 8 weeks. The disease occurring during this intoxication resulted mainly from injury to the kidney, and the renal function tests demonstrated a pronounced fall in kidney function in the pigs on the high dose level. Accordingly, changes in renal structure were found in these pigs consisting of tubular degeneration and excessive connective tissue formation. Tissue analysis for mercury showed a distribution between the organs similar to that characteristic for inorganic mercury, indicating a rapid metabolism of methoxyethyl mercury. The renal excretion of mercury seemed to increase with time of exposure but never exceeded ten per cent of the inulin clearance.     

l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury

Inorganic mercury (HgCl₂) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl₂ exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl₂ exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.     

Exogenous metallothionein and renal toxicity of cadmium and mercury in rats.

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.