SAS probit analysis for cadmium mortality

In the quantitation of heavy metal effectiveness it is useful to compute the median lethal dose (LD₅₀) to the exposed population. The computerized Statistical Analysis System (SAS) of probit analysis is particularly useful in analyzing dose-response data because it is more accurate than the graphical methods currently in use and, in addition, provides fiducial limits with its estimates. Acute and chronic cadmium mortalities of young adult male and female Sprague-Dawley rats were determined by the SAS probit analysis. When male and female rats were administered comparable doses of cadmium chloride, based on individual body weights, males were more susceptible. A plausible explanation for this greater sensitivity of males to the heavy metal is testicular necrosis. The acute LD_{50 (30 days)} value for males was 5.99 mg Cd/kg body wt, with 95% fiducial limits of 4.71-7.54 mg Cd/kg body wt, as compared to 7.13 (5.18-8.85) mg Cd/kg body wt for females. When multiple (chronic doses of cadmium were injected, LD_{50 (30 days)} values were 4.25 (3.42-5.05) mg Cd/kg body wt and 5.14 (4.42-5.92) mg Cd/kg body wt for males and females, respectively. Values calculated 30 days after the last injection (at Day 60) were 3.38 (2.61-4.05) mg Cd/kg body wt and 4.65 (4.00–5.25) mg Cd/kg body wt for males and females, respectively. Chronic LD values indicate an increase in effectiveness of dose as time of injections was protracted.     

甘草甜素和齐墩果酸对大鼠镉中毒性肝损伤的防护作用与机理

为探讨甘草甜素(GL)和齐墩果酸(OA)对大鼠镉中毒性肝损伤的防护作用及其作用机理,给大鼠腹腔注射CdCl₂溶液(0.8mgCd²⁺/kg体重),两组染镉大鼠分别同时皮下注射GL的生理盐水溶液(20mg/kg,每周3次)和OA的吐温-生理盐水混悬液(60mg/kg,每周5次),测定血清转氨酶、肝镉(Cd)、金属硫蛋白(MT)含量,检查肝组织病理形态学.结果显示:GL和OA延缓、降低了镉引起的血清转氨酶的升高,显着减轻了肝细胞肿胀、坏死及肝线粒体、滑面内质网病变的程度,明显减少了染镉初期镉在肝脏的蓄积,显着提高了肝内诱导的MT量.提示GL和OA对大鼠镉中毒性肝损伤有防护作用,此作用可能与其减少染镉初期镉在肝脏的蓄积及诱导MT或促进镉对MT的诱导有关.     

异搏定和氯丙嗪对镉慢性肾毒性影响的实验研究

目的:对慢性镉染毒(Cd)大鼠投予异搏定(Ver)和氯丙嗪(CPZ),探讨这两种物质对镉慢性肾损伤的影响。方法:实验用4组大鼠,单纯镉染毒组和Ver、CPZ预处理组均皮下注射含Cd 1．4mg／kg的氯化镉(CdCl2)溶液,每周3次,连续6周。Ver和CPZ预处理组在每次皮下注射CdCl2前1h,分别向腹腔注射Ver 4mg／kg和CPZ 5mg／kg,,对照组大鼠在相同时间注射生理盐水5ml／kg,,在实验开始后第2,4,6周时收集尿样,测定尿N-乙酰-B—D-氨基葡萄糖苷酶(NAG)活力和尿蛋白含量。最后一次注射后24h处死大鼠,采集血液,取肾脏,测定血清尿素氮(BUN),血、肾皮质和尿中的Cd、Ca及血、肾皮质中丙二醛(MDA)含量。结果镉染毒4周时,与单纯镉染毒组比较,Ver和CPZ预处理组的尿NAG活力和尿蛋白含量均明显降低;镉染毒6周时,Ver和CPZ预处理组的血Cd、血清BUN、尿Ca及肾皮质MDA含量均明显降低。CPZ预处理组肾皮质Cd和血MDA含量也明显降低。结论:Ver和CPZ具有防止镉所致慢性肾损伤的作用,其机制可能是减轻镉对肾脏的脂质过氧化损伤。     

皮下注射丙烯腈对大鼠致畸作用研究

目的　评价丙烯腈对雌性大鼠有无致畸作用。方法　于雌性大鼠妊娠第 7～ 16天皮下注射丙烯腈 (AN) 15 ,2 5 ,35mg·kg-1,常规方法检测AN的胚胎毒性和致畸作用。结果　 2 5mg·kg-1组死胎率、吸收胎率升高 ,胎鼠平均体重、体长、尾长减小 ,与阴性对照组比较差异有显著性 (P <0 0 5 ) ;35mg·kg-1组除窝平均活胎数减少 ,差异有显著性 (P <0 0 5 ) ,其余各指标与阴性对照组比较差异有非常显著性 (P <0 0 1) ;2 5 ,35mg·kg-1组畸胎率、母体畸胎率、活胎畸形率升高 ,与对照组相比差异有显著性和 /或非常显著性 (P <0 0 5或P <0 0 1) ,且有明确的剂量效应或剂量反应关系。本实验皮下注射AN染毒的致畸最低剂量为 15mg·kg-1,致畸指数为 6 3,以骨骼畸形为主 ,外观畸形主要为无尾、短尾等。结论　丙烯腈皮下注射染毒有明显的胚胎毒性 ,致畸剂量小于经口染毒阈剂量 ,是一种弱致畸物。     

亚硒酸钠对镉和汞肝肾氧化损伤影响的实验研究

目的:观察一次染镉和汞对大鼠肝、肾组织氧化损伤作用,探讨亚硒酸钠预处理对镉和汞氧化损伤的影响。方法:Wister大鼠48只,随机分成6组,每组8只,第1组为染镉实验对照组,第2组为单纯染镉组,第3组为亚硒酸钠预处理组,第4组为染汞实验对照组,第5组为单纯染汞组,第6组为亚硒酸钠预处理干预组。第1、4组大鼠先腹腔注射生理盐水,2 h后皮下注射生理盐水。第2组大鼠先腹腔注射生理盐水,2 h后皮下注射35μmol/kg氯化镉溶液。第3组大鼠先腹腔注射10μmol/kg亚硒酸钠溶液,2 h后皮下注射35μmol/kg氯化镉溶液。第5组大鼠先腹腔注射生理盐水,2 h后皮下注射2.5 mg/kg HgCl2溶液,第6组大鼠先腹腔注射20μmol/kg亚硒酸钠溶液,2 h后皮下注射2.5 mg/kg HgCl2溶液。染毒24 h后测定肝、肾皮质镉或汞、谷胱甘肽、丙二醛含量和谷胱甘肽过氧化物酶活性。结果:与对照组比较,单纯染镉组大鼠肝GSH、MDA含量显著升高,GSH—Px活性显著下降。Na2SeO3预处理组肝、肾皮质GSH和镉含量显著降低,肝脏GSH—Px活性及肾皮质MDA含量显著升高。单纯染汞组大鼠肝、肾皮质及尿汞含量均显著高于对照组。单纯染汞组肝MDA含量显著高于对照组,GSH含量和GSH—Px活性显著低于对照组。Na2SeO3预处理组的肝脏GSH含量和GSH—Px活性均较单纯染汞组升高,有显著性差异。单纯染汞组肾皮质MDA含量显著高于对照组,GSH含量和GSH—Px活性显著降低。Na2SeO3预处理组中肾皮质MDA含量低于单纯染汞组,GSH—Px含量高于单纯染汞组。结论:给大鼠一次染镉和汞,可以对肝和肾脏产生明显的氧化损伤作用。亚硒酸钠对急性染镉和汞所致肝肾损伤具有一定的拮抗作用,其机制可能与增加内源性GSH、使GSH—Px活性增强以及清除自由基能力提高有关。     

Cytological shift in lymphocytes induced by cadmium in mice and rats

The hematological response as well as the clinical response such as retarded growth, polyuria, and proteinuria in cadmium poisoning was investigated in mice given a daily subcutaneous injection of sublethal doses of cadmium (below 2 mg Cd/kg) for 1 to 7 weeks and in rats exposed daily to an inhalation of cadmium oxide fumes (0.1 and 1.0 mg CdO/m³) for 4 weeks. Besides a usual tendency toward neutrophilia and lymphopenia in cadmium poisoning, a significant cytological shift of lymphocytes to large lymphocytes was found in the cadmium-treated mice and rats under extended cadmium exposure. This alteration in lymphocytes was observed earlier than anemia and the other responses. It was apparent already 1 week after initiation of cadmium injection and was amplified when the administration was further prolonged. This cytological shift also depended on the dose of cadmium (0.0625 to 2 mg Cd/kg) at week 1. The increase of large lymphocyte counts was accompanied by the decrease of small lymphocyte counts and by the increase in spleen weight. These findings in lymphocytes indicate that cadmium may affect the immune system directly or compensatorily. Differential counts of lymphocytes could be a useful clinical indicator for early detection of adverse effect of environmental and industrial exposure to cadmium.     

Marginal nutritional status of zinc, iron, and calcium increases cadmium retention in the duodenum and other organs of rats fed rice-based diets

Dietary minerals Zn, Fe, and Ca are antagonistic to Cd absorption. We showed earlier that rats fed a rice-based diet with a marginal content of these nutrients absorbed more Cd than rats fed adequate Zn-Fe-Ca (Environ. Sci. Technol., 36 (2002) 2684-2692). The present experiment was designed to determine the effects of marginal dietary Zn, Fe, and Ca on the uptake and turnover of Cd in the gastrointestinal tract. Two groups of weanling female rats (six per treatment) were fed a diet containing 40% cooked, dried rice containing 0.6 mg Cd/kg. The diet of one group contained adequate Zn (35 mg/kg), Fe (30 mg/kg), and Ca (5000 mg/kg), while that of the other group contained marginal Zn (6 mg/kg), Fe (9 mg/kg), and Ca (2500 mg/kg). Rats were fed for 5 weeks and then orally dosed with 1g of diet containing rice extrinsically labeled with 109Cd. From 0.25 to 64 days after dosing, 109Cd and total Cd concentrations were determined in intestinal segments. Shortly after dosing, 109Cd, as a percentage of the dose, was about 4 times higher in the duodenum of marginally fed rats than in that of control rats (10% vs 40%, respectively). Sixty-four days after dosing, 109Cd was 10 times higher in marginally fed rats than in controls; however, of the amount at day 1, <0.1% remained at day 64. After 5 weeks, the concentration of elemental Cd in the duodenum of the marginally fed rats was 8 times higher than that of control rats (24 microg/g dry wt. vs 2.9 microg/g dry wt., respectively). Cd concentrations in liver and kidney were 5 times higher in the marginally fed rats than those in controls (liver, 0.81 microg/g dry wt. vs 0.14 microg/g dry wt.; kidney, 4.7 microg/g dry wt. vs 0.92 microg/g dry wt., respectively). These data suggest that marginal intakes of Zn, Fe, and Ca cause the accumulation of Cd in the duodenum, which results in a greater rate of Cd absorption and a greater accumulation in the internal organs. Results are discussed in relation to mineral nutrient status and risk assessment of Cd in natural food sources.     

Blood pressure and urinary sodium and potassium excretion in cadmium-treated male rats

Subcutaneous injection of cadmium chloride (as CdCl2) in the backs of male Wistar rats at the four doses of 0.01, 0.1, 0.5, and 1.0 mg/kg body wt was performed twice a day for 7 consecutive days and the animals were maintained without any treatment for an additional period up to 60 days. Treatment with 0.1, 0.5, and 1.0 mg Cd markedly decreased the urinary Na and K excretion from Day 1 to Day 3. The significant increase in blood pressure of rats treated with 0.1 mg Cd was not present from Day 8 to Day 32 during which the water retention significantly increased. The blood pressure of rats treated with 1.0 mg Cd significantly increased although the increase in water and Na retention was not observed on Day 32. These observations suggest that the decrease in the urinary excretion of Na and the increase in water retention may be not associated with the main factor for the elevation of the blood pressure induced by Cd. Cd concentrations in the heart, abdominal aorta, and lung of rats treated with 1.0 mg Cd were markedly lower than those in the liver and kidney. Changes in the level of Ca and Mg were only observed in the lung and not in the heart and aorta.     

Mitochondrial effects of low-level cadmium in rats: Interaction with zinc

Male Sprague-Dawley rats were treated with sodium or cadmium (Cd) 4 acetate (25 g Cd per kg body weight) orally 5 times a week for 6 weeks. A second group of animals was repeatedly injected with zinc sulphate (6 and 12 mg zinc (Zn) per kg ip) with or without Cd gavage. Cadmium treatment alone yielded no obvious toxic effects as evidenced by serum constituents or animal weight gain. Similarly, Zn injection did not affect these criteria. Zinc injection increased metallothionein in liver and kidneys and increased renal Cd. Cytosolic sorbitol dehydrogenase was not influenced by either cadmium, Zn or Cd + Zn exposure. However, individual Cd gavage decreased mitchochondrial cytochrome c oxidase in liver by 50%. This was partly protected by Zn. Hepatic adenosine triphosphatase (ATPase) was not affected by any of the treatment regimens. However, renal ATPase was inhibited by combined Cd + Zn administration. The data suggest subcellular toxic effects due to treatment with low Cd doses as evidenced by the decrease in hepatic cytochrome c oxidase. Simultaneous Zn injection may reduce this effect of Cd in liver. However, the treatment of rats by low level Cd gavage combined with zinc administration impairs the animals' health as shown by weight loss.Abbreviations Cd cadmium - Zn zinc - ATP adenosine triphosphate - ATPase adenosine triphosphatase - MT metallo thionein - NADH nicotinamide adenine dinucleotide, reduced Parts of this study have been presented at the 20th Annual Meeting of the Australasian Society for Clinical and Experimental Pharmacologists (ASCEP), Dec 8–10, 1986, Melbourne.     

Uptake and distribution of Cd in the ovaries, adrenals, and pituitary in pseudopregnant rats: effect of Cd on progesterone serum levels

Pseudopregnant (PSP) rats were treated with 3.5 or 7.0 mg/kg body wt of CdCl2 on Day 1 of PSP sc. In the lower dose Cd content of the ovaries (luteal and nonluteal tissues), adrenals, pituitary, and blood on Days 1, 2, 5, 8, 10, and 12, and in the higher dose that of luteal and nonluteal tissue on Days 2 and 5 of PSP were determined with atomic absorption spectrophotometry. A rapid incorporation into the corpora lutea was measured on Day 1 and Day 2 of PSP followed by a decrease of Cd content toward the end of PSP whereas the nonluteal tissue, adrenals, and pituitary accumulated Cd gradually until the fifth to 10th day, respectively. Progesterone (P) serum levels were measured with RIA in the blood collected daily from the jugular vein following administration of 3.5 to 7.0 mg/kg body wt of CdCl2 sc on Day 1 or Day 8 of PSP. The serum levels of P remained unchanged when CdCl2 was administered on Day 1 of PSP; however, 7.0 mg/kg body wt CdCl2 given on Day 8 of PSP induced a significant decrease in serum levels of P. It is supposed that the regressing luteal tissue is more sensitive to the toxic effects of Cd than the developing one.     

茶多酚、维生素C对镉肾毒性影响的实验研究

目的 研究茶多酚(TP)、维生素C(Vc)对镉肾毒性的影响。方法 将Wistar大鼠40只，随机分成4组。第1组为对照组，第2组大鼠皮下注射1．44mg／kg氯化镉溶液；第3、4组大鼠以TP、Vc预处理后皮下注射1．44mg／kg氯化镉溶液，每周3次，连续6周。分别在实验开始后第4周和6周时将大鼠移入代谢笼，收集24h尿样，分别测定尿N-乙酰-P-氨基葡萄糖酶(NAG)活性和尿蛋白、尿镉含量。于最后一次注射24h后处死大鼠，采集血液和肾皮质样品。测定各组大鼠血清尿素氮、血及肾皮质的丙二醛(MDA)含量，血及肾皮质镉含量。结果 染镉4周后，与单纯染镉组比较，TP和Vc能明显降低尿NAG酶活性和尿蛋白含量。染镉6周后，TP和Vc能显降低血清尿素氮、血及肾皮质MDA含量。TP还能显降低血、肾皮质镉及升高尿镉含量。结论 TP、Vc预处理对镉中毒所致的肾损伤有一定的预防作用，此种预防作用可能与它们的抗氧化作用及促进镉排泄有关。     

Retention of cadmium in cadmium-naive normal and iron-deficient rats as well as in cadmium-induced iron-deficient animals

The retention of cadmium was investigated in cadmium-naive normal and iron-deficient rats in comparison to rats with cadmium-induced iron deficiency. Rats subchronically (4 weeks) exposed to dietary cadmium (28, 56, 112 ppm Cd and 28 ppm Fe) received a radioactively labeled dose of 2 mumol Cd/kg body wt; acutely (no cadmium exposure with diet) treated rats received doses between 1 and 8 mumol Cd/kg body wt. Two animals of each group received iron (1 mumol/kg as 59FeSO4 in order to monitor iron absorption in parallel. After a period of 4 weeks of feeding a cadmium-fortified diet, the test dose was administered and after a 2-weeks period 109Cd and of 59Fe retention was determined. The results showed in part an unexpected pattern of cadmium retention: subchronic feeding of cadmium induced iron deficiency. This implies an immediate interaction between the two metals with regard to intestinal transfer of iron. The retention of iron was increased in the Cd-induced anemia to the same extent as that in iron deficiency induced by iron restriction. Cadmium retention in iron deficiency induced by iron withdrawal also showed a marked increase, which implies that iron deficiency stimulates the intestinal transfer system for both metals in a similar way. Contrary to this effect, the cadmium retention in cadmium-induced iron deficiency was reduced to about 30% of control values. A self-induced aggravation of the body cadmium burden, as a consequence of the iron deficiency which is known to result from subchronic exposure to feeding of dietary cadmium, was thus excluded.     

Effect of zinc deficiency on the accumulation of metallothionein and cadmium in the rat liver and kidney

The effects of zinc (Zn) deficiency and repeated exposure to cadmium (Cd) on the accumulation and distribution of metallothionein (MT), Cd and Zn in the liver and kidney were studied. Male Sprague-Dawley rats were fed either a Zn-deficient (1 ppm) or a Zn-adequate (40 ppm) diet during the experiment, and the rats were injected subcutaneously with a cadmium chloride solution (1.0 mg Cd/kg of body weight, 5 days a week) for 4 weeks. Cadmium, Zn, and Cd-induced MT concentrations in the liver and kidney were lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), while the content of Cd bound to high molecular weight proteins (HMWP) was greater in the Zn-deficient rats (–Zn + Cd). The Zn bound to Cd-induced MT was reduced to 30% in the liver and to 60% in the kidney of the Zn-deficient rats (–Zn + Cd) as compared with that of the Zn-adequate rats (+ Zn + Cd). In the kidney of Zn-deficient rats, exposure to Cd caused a decrease in essential Zn associated with HMWP as compared with that of Zn-adequate rats (+ Zn + Cd). Thus, Zn-deficiency affected the distribution of Cd in tissues, MT and HMWP and accelerated substantially Cd-induced Zn-deficiency in the kidney. Although the renal Cd concentration was lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), exposure to Cd for four weeks resulted in glucosuria and an increase in liver and kidney weights in the Zn-deficient rats (–Zn + Cd), but not in the Zn-adequate rats (+ Zn + Cd). These results suggest that development of Cd toxicity is related to the Zn status of the body, to the accumulation of Cd in HMWP and to the amount of essential Zn associated with HMWP.     

The role of enzyme induction on metabolite formation of bis(2-methoxyethyl) ether in the rat

The effect of enzyme induction on the metabolism of the reproductive toxicant bis (2-methoxyethyl) ether (diglyme) was studied in male Sprague-Dawley rats. Rats were given either daily doses of diglyme at 5.1 mmol/kg body wt. by gavage or 0.1% (w/v) phenobarbital (PB) in the drinking water for 22 consecutive days. In one study, a significant reduction in the hexobarbital sleeping time was determined for rats pretreated with diglyme or PB in comparison with that determined for naive rats. In a second study, naive and pretreated rats given single oral doses of 14C-diglyme at 5.1 mmol/kg body wt. showed similar urinary 14C excretion patterns. Urinary metabolites were separated and quantified by hplc to evaluate the influence of pretreatment with either diglyme or PB on the 14C-diglyme urinary metabolite profile. The amount of (2-methoxyethoxy) acetic acid, the principal metabolite, was similar for rats given no pretreatment and for rats pretreated with either diglyme or PB. However, both pretreatments resulted in significant increases in the formation of methoxyacetic acid, a recognized reproductive toxicant.     

Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.     

The effects of zinc deficiency on turnover of cadmium-metallothionein in rat liver

The object of this experiment was to determine the effects of Zn deficiency on the turnover of Cd-induced metallothionein (MT) in rat liver. Male rats were fed a purified Zn-deficient or Zn-adequate diet. After 13 days, the rats were given three daily injections of Cd2+ totaling 1.5 or 3.0 (Zn-deficient) and 3.0 or 6.0 (Zn-adequate) mg Cd/kg body weight. The MT was labeled by injecting the rats with [35S]cystine 2 hours after the final Cd injection. One, 3 or 5 days after labeling, the rats were killed, and their livers were assayed for MT 35S and metal content. The metal composition of MT (mole %) was 41-42% Cd, 51-54% Zn and 4-7% Cu in the Zn-adequate groups and 64% Cd, 27-31% Zn and 6-9% Cu in the Zn-deficient groups. The half-lives of Cd-induced MT in the Zn-deficient rats were 2.6 days (1.5 mg Cd/kg) and 2.8 days (3.0 mg Cd/kg). In the Zn-adequate rats, the half-lives were 3.6 days (3.0 mg Cd/kg) and 3.1 days (6.0 mg Cd/kg). The half-lives of general, soluble hepatic proteins were 4.1 to 4.3 days in all groups. Despite the stabilizing effect of the higher Cd content, the half-life of hepatic MT in the Zn-deficient rats was significantly shorter than in the Zn-adequate rats. These results indicate that hepatic MT degradation is faster in Zn-deficient animals.     

亚急性丙烯腈染毒对小鼠肝脏和血液中微量元素的影响

[目的]采用亚急性试验研究丙烯腈(AN)对小鼠组织微量元素的影响,为评价AN的毒作用机制提供依据。[方法]选用32只小鼠,雌雄各半,随机分成对照、低、中、高剂量4组,每组8只,分别给予AN0、5、10、20mg/kg,腹腔注射染毒,每天1次,连续染毒1周。观察动物的行为变化,称量体重,计算脏器系数,用火焰原子吸收法测定肝脏、血液微量元素Fe、Zn、Cu的含量,原子荧光法测定Se含量。[结果]各组肝体系数无显著性差别,但随着染毒剂量的增高有下降趋势,脑体系数出现升高趋势,高剂量组明显高于对照组和低剂量组;与对照组比较,中等剂量组肝脏Zn、Cu的含量均有显著增高,中等剂量组血液Zn含量与对照组及低剂量组相比有明显升高;肝脏Zn/Cu比例呈现降低趋势,肝脏和血液中Fe、Se含量染毒组与对照组差别无显著性。[结论]丙烯腈对小鼠组织中Zn、Cu含量影响较为显著,微量元素失衡可能是AN毒作用的重要机制。     

金属硫蛋白与镉中毒性肝肾损害的关系

目的观察亚慢性镉中毒性肝肾损害,并初步探讨金属硫蛋白（ＭＴ）与肝肾损害的关系。方法用Ｗｉｓｔａｒ大鼠腹腔注射０．５ｍｇ／ｋｇＣｄ２＋的ＣｄＣｌ２３次／周,共１０周,染毒后不同时期处死大鼠,观察肝肾功能变化。结果染毒６周后,大鼠出现了明显的肝肾损害,相应组织中Ｃｄ∶ＭＴ的摩尔数之比均超过７,且随染毒总剂量的增加,Ｃｄ∶ＭＴ值明显增加,病变程度加重。结论肝肾是亚慢性镉中毒的靶器官,非ＭＴ结合的镉可能是损害肝、肾的主要成分。     

Toxicity,fertility, teratogenicity,and dominant lethal tests in rats administered cadmium subchronically: I. Toxicity studies

In order to obtain an overall understanding of the toxicity of cadmium (Cd), a single experimental series was designed to investigate the diverse effects of Cd. Four groups of Sprague-Dawley rats, each of which consisted of 14 male and 14 female rats, were administered Cd (CdCl₂) orally at dose levels of 0, 0.1, 1.0, 10.0 mg/kg/day for 6 weeks. After this, the animals were mated for 3 weeks, changing partners every week, for fertility and teratogenicity tests. Cd was given during this mating period. Females were administered Cd during gestation and sacrificed on the 20th day of gestation for fetal examination. After a total of 9 weeks administration, males were subjected to dominant lethal tests by mating 2 females per male per week for 6 weeks. Pregnant females were killed on the 13th day of gestation to test for dominant lethality. This paper reports the results of the general toxicity tests. The main toxic signs, seen only in the 10 mg/kg group, were repression of food intake and body weight gain, depilation, whitening of the incisors, and salivation. Hematological analyses showed that the number of RBC increased while hemoglobin and hematocrit levels decreased, and the number of WBC increased, mainly as a result of neutrophilia. Serum biochemical analyses indicated increased levels of GPT and creatinine, reflecting damage to the liver and kidneys. Increased glucose levels were seen in males. A major change found at the time of autopsy by macroscopic observation of organs was hypertrophy of the jejunum and ileum with a darkish-brown color in nonpregnant females of the 10 mg/kg group. Microscopically, hyperplasia with a high frequency of mitotic figures was seen in the lamina propria mucosae. The weight of the thymus decreased and the weight of the adrenals increased in both males and females. The weight of the ovaries decreased. Major histopathological changes were focal necrosis in the liver and hyperplasia of the adrenal cortices with patchy necrosis in nonpregnant females of the 10.0 mg/kg group. Determination of Cd in the liver and kidneys suggested that excretion of the accumulated Cd was slow. Two aspects of Cd toxicity, i.e., the inhibition of nutrient resorption by unresorbed Cd and the toxicity expressed by resorbed Cd, as well as the causative factors of the adrenal hyperplasia, are discussed.     

Route of delivery of phenylalanine influences its effect on short-term food intake in adult male rats

The effect of phenylalanine (Phe) on plasma and brain Phe and tyrosine (Tyr) levels and on short-term food intake in male rats was measured after intragastric (i.g.), subcutaneous (s.c.) and intraperitoneal (i.p.) administration. Compared to equimolar alanine (Ala), which served as the control, Phe significantly suppressed feeding at a dose of 90 mg/kg body wt when given i.p., but doses up to 720 mg/kg body wt had no effect when given i.g. or s.c. The high doses of Phe given by the i.g. or s.c. route resulted in higher levels of Phe in both plasma and brain than those following i.p. injection (90 mg/kg body wt). Furthermore, brain Tyr levels after i.g. Phe (720 mg/kg body wt) were equal to or higher than after i.p. Phe (90 mg/kg body wt). We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations.