Injection Of Cadmium Chloride Research Articles

Effects of Nitrofurantoin and Cadmium Chloride on Spermatogenetic Activity in an Avian Pest, the Yellow-throated Sparrow(Petronia xanthocollis Burton).

Oral administration of nitrofurantoin (200mg/kg body weight daily for 5 days) caused reduction in testis weight, seminiferous tubular diameter, and secondary spermatocyte and spermatid populations in the yellow-throated sparrow (Petronia xanthocollis, Burton). Spermatozoa bacame less abundant, but Leydig cell nuclear area, 3β-HSDH activity and sialic acid content of the testis remained unaltered after treatment. Single intraperitoneal injection of cadmium chloride (0.05mg/kg body weight) failed to produce any perceptible effect on the testis of the yellow-throated sparrow.It is suggested that nitrofurantoin has an antispermatogenetic effect in the yellowthroated sparrow. But cadmium chloride, at least with the dose administered, has no effect on the testis of this avian species. Moreover, both the chemosterilants have no effect on gonadotrophic activity or testicular steroidogenic activity in the yellow-throated sparrow.

Effects of procymidone on reproductive organs and serum gonadotropins in male rats.

To investigate the mechanism and toxicological significance of testicular interstitial cell tumors (ICT) observed in a long-term rat study with procymidone, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximi de, male Sprague-Dawley rats were fed procymidone in diets for up to 6 months with a positive control group receiving a single subcutaneous injection of cadmium chloride. Examinations mainly for gonadal functions such as serum testosterone and luteinizing hormone (LH), reproductive organ weight and histopathology presented evidence of the indirect involvement of gonadotropins in the production of ICT in rats. A significant increase in both serum testosterone and LH was observed in the early stage at high dietary concentrations of procymidone without any lesion in gonadal systems in histopathology, whereas administration of cadmium chloride produced the expected substantial increase in serum LH and a concomitant decrease in serum testosterone with a marked damaging effect on gonadal systems. Increases in serum testosterone and LH levels in animals receiving procymidone were reversible. The no-effect level for procymidone on serum testosterone and LH was 300 ppm over six months of treatment. The possible mechanism of ICT production in rats by non-genotoxic procymidone, structurally similar to flutamide, a synthetic non-steroidal antiandrogen, is likely to be derived from its induction of a hypergonadotropism due to the competitive binding to the androgen receptor, preventing the normal effect of testosterone to control the circulating level of LH.

Characteristics of cadmium-induced nephrotoxicity in Syrian hamsters.

Male Syrian hamsters were used to evaluate cadmium (Cd)-induced nephrotoxicity. Furthermore, they were treated with polyaspartic acid (PAA) in an attempt to prevent renal damage due to Cd. To induce renal proximal tubular damage, the hamsters were administered a single subcutaneous injection of cadmium chloride (CdCl2) at the dose of 3 mg/kg body weight. Within 24 hours, they exhibited significant proteinuria and an increased urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Renal histological changes consisted of degenerative changes in renal tubule cells, irregularly shaped nuclei with marginated chromatin and rounded mitochondria. The administration of PAA did not improve creatinine clearance or urinary protein excretion. The concentration of Cd in the renal tissue showed a gradual increase on day 3 following cadmium exposure. Cadmium nephrotoxicity appears to be more severe in Syrian hamsters than in rats or mice. Thus, this animal model appears to be excellent for studying Cd-induced nephrotoxicity.

Pancreatic hepatocytes in Fischer and Wistar rats induced by repeated injections of cadmium chloride

The effects of multiple sc injections of cadmium chloride (CdCl 2) on the pancreas of two rat strains (Wistar [WF/NCr] and Fischer [F344/NCr]) were studied by histological and immunohistochemical examinations. A high incidence of hepatocytic foci occurred within the pancreata of both strains that was associated with this cadmium exposure. Although pancreatic hepatocytes (PH) were found in both strains, Wistar rats were more susceptible to cadmium-induced PH formation while showing more tolerance to cadmium in general. The highest incidence of PH was 93% in Wistar rats and 50% in Fisher rats. Dose-related increases in incidence of PH occurred at levels of 360–513 μmol Cd/kg. Number of PH foci/rat correlated well with PH incidence. By avidin-biotin immunohistochemistry, PH exhibited rat albumen and a gap junction protein (Connexin32) found in hepatocytes. PH were frequently seen along with pancreatic acinar atrophy (fatty replacement) and interstitial fibrosis. Thus, it appears that cadmium must be considered one of the most efficacious agents for production of PH within the rat pancreas. The ability of cadmium to induce this transdifferentation is also clearly dose and strain related.

Cadmium-induced ovarian toxicity in hamsters, mice, and rats

The effects of cadmium on the female genital tract of Syrian hamsters (Cr:RGH), of four mouse strains ( BALB cAnNCr , DBA 2NCr , C57BL 6NCr , NFS NCr ), and two rat strains ( F344 NCr and WF NCr ) were studied by light microscopy after a single sc injection of cadmium chloride (CdCl 2). Experiments involved animals prior to and after sexual maturity, and employed CdCl 2 doses ranging from 20 to 47.5 μmol/kg. Animals were examined at intervals from 24 hr to 8 weeks following treatment. Syrian hamsters were most susceptible to CdCl 2-induced ovarian hemorrhagic necrosis at all ages tested. Most severe ovarian lesions occurred in immature hamsters, in mature hamsters at high doses, and shortly before ovulation at all doses. The small arteries of the developing follicles and interstitial stroma seemed selectively susceptible to CdCl 2 toxicity while the corpora lutea, mesothelium, primordial oocytes, and the rete ovarii appeared resistant. Pretreatment with zinc acetate markedly reduced the extent of ovarian lesions in hamsters. Although reduced in weight by 45%, the hamster ovaries recovered morphologically within 2 months after severe acute hemorrhagic necrosis. Uterine and cervical stromal hemorrhages were seen only in immature hamsters at doses of ≥ 30 μmol CdCl 2/kg. Of the mice, only the DBA 2NCr strain showed significant CdCl 2-induced ovarian hemorrhages, and these hemorrhages occurred at doses also producing lethal liver toxicity. Lesions of the uterus were rare. Rats showed dose- and age-dependent toxicity in the ovaries, uterus, cervix, and liver. CdCl 2 exposure in mature rats induced uterine lesions only in F344 rats, while acute ovarian and hepatic toxicity was less severe in mature animals of both strains. No lesions were noted after 7 days in mature WF rats. In both rats and mice, no cycle dependency of the ovarian lesions was evident.

Cadmium chloride-induced changes in hypothalamic 5-hydroxytryptamine, noradrenaline and dopamine levels in the Indian palm squirrel, Funambulus pennanti (Wroughton)

A single intraperitoneal injection of cadmium chloride (CdCl 2, 0.32 mg/kg body weight) was administered to 15 adult female palm squirrels ( Funambulus pennanti (Wroughton)) and the hypothalamic 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) levels were quantified on the 1st, 7th and 40th day. 5-HT levels significantly decreased on the 1st and 40th day but showed an increase on the 7th day. Similarly, NA levels significantly decreased after 1, 7 and 40 days of treatment, and DA levels decreased on the 1st and 7th day but insignificantly increased on the 40th day. This suggests that CdCl 2 interferes in the functioning of the hypothalamo-hypophyseal axis by impairing the hypothalamic 5-HT, NA and DA levels, which may in turn affect the physiology of the peripheral endocrine glands.

Cadmium exposure in infancy: Effects on activity and social behaviors of juvenile rats

In two experiments male and female infant rats were given single injections of cadmium chloride (0, 1, 2, 3 or 4 mg Cd/kg) on Day 5 or 6. Animals receiving the 3 and 4 mg/kg doses had high mortality rates at weaning; survivors were extremely underweight and were not used in postweaning tests. Male subjects receiving 2 mg/kg in infancy were significantly more active after weaning than littermates who had received 0 or 1 mg/kg doses, and on Day 29 they also engaged in significantly more rough and tumble play with a nontreated partner than did rats in the other groups. This effect of early cadmium exposure was also evident when males were tested with similarly treated subjects on Day 44: rats in the 2 mg/kg group had higher pinning frequencies than rats in the 0 or 1 mg/kg groups. In contrast, females in the 1 and 2 mg/kg groups did not have increased activity or rough and tumble play fighting. These data are consistent with the few correlational studies in human children which suggest changes in social behaviors associated with elevated tissue cadmium levels.

Induction of metal binding proteins in striped bass, Morone saxatilis, following cadmium treatment

1. 1. The time course of induction of cytosolic metal binding proteins (MBP) was observed following up to three daily intramuscular injections of cadmium chloride (0.2 mg cadmium/injection). 2. 2. Low molecular weight binding proteins were resolved by gel permeation chromatography on Sephadex G-75. Based on total metal binding capacity, the concentration of crude MBP increased 2.6 fold. This level of induction of MBP was confirmed by polarographic analysis. 3. 3. Initial binding of cadmium to MBP resulted in displacement of zinc, while at later times, zinc associated with MBP increased above control levels. 4. 4. Using 35S-cysteine incorporation, it was shown that the rate of hepatic MBP synthesis was significantly greater than controls and sham injected fish 18 hr after the third cadmium injection. 5. 5. Due to interfering proteins of molecular weights similar to the metal binding proteins one dimensional PAGE was not capable of verifying induction. However, the metal binding proteins were resolved using two dimensional gel electrophoresis.

High-performance liquid chromatography-inductively coupled plasma profiles of cadmium, zinc, sulphur and other elements in rat liver supernatants after cadmium injection

The distribution of cadmium zinc sulphur and other elements in the liver supernatants of rats and their variation with time following a single intraperitoneal injection of cadmium chloride were characterized by high-performance liquid chromatography (HLPC) coupled with an inductively coupled plasma. Cadmium that was bound to high-molecular-weight-proteins before the induction of metallothionein was analysed more easily using an Asahipak GS-520 column whereas the distributions of other elements and of cadmium bound to metallothionein were better characterized on a TSK G3000SW column. Cadmium bound primarily to a distinct high molecular-weight protein before the induction of metallothionein. After the injection its distribution shifted with time to metallothionein. An atomic emission spectrometer employing an inductively coupled argon plasma and a vacuum UV monochromator was effectively used as a multi-element specific detector for HPLC.

Cadmium, zinc, and copper in rabbit kidney metallothionein—relation to kidney toxicity

Twenty-two rabbits were given repeated subcutaneous injection of cadmium chloride. The cumulative cadmium dose given ranged from 13 to 214 mumole/kg body weight. Five rabbits served as controls. The treatment resulted in cadmium concentrations in kidney cortex that ranged from 0.3 to 3.2 mmole Cd/kg and a subsequent production of metallothionein. The molar ratio of cadmium, zinc, and copper in metallothionein fractions from kidneys with different concentrations of cadmium was determined. At low concentrations of cadmium in rabbit kidneys, zinc was the dominating metal bound to metallothionein (70-90%). At high concentrations of cadmium in kidneys, cadmium was the dominating metal in metallothionein. Evidence of kidney toxicity, in the form of beta2-microglobulinuria, was seen when cadmium constituted 85% of the metal ions recovered from metallothionein fractions. The remaining 15% was zinc. This indicates that at most six of the seven metal-binding sites in mammalian metallothionein are occupied by cadmium and that the remaining site is occupied by zinc. Our data provide further support for the hypothesis that chronic cadmium nephrotoxicity develops when there is a lack of metal-binding sites available for cadmium in metallothionein.

Abnormalities of the ear associated with exencephaly in mouse fetuses induced by maternal exposure to cadmium.

Exencephaly was induced in mouse fetuses by maternal injection of cadmium chloride (CdCl2) on day 7 of gestation. The heads of exencephalic, nonexencephalic experimental, and control fetuses were embedded in paraffin and sections were stained with hematoxylin and eosin. Compared to those of controls, the ears of the exencephalic fetuses were smaller (microtia) and low set. The meatal plug representing the external auditory canal was thick, variously branched, and often directed inferiorly. Usually, there were just two ossicles. The stapedial artery, facial nerve, and stapedius muscle were hypoplastic; the tensor tympani was small or absent. There were 1.0 to 2.0 turns of the cochlea in contrast to 2.5 turns in the controls. The organ of Corti was underdifferentiated; the spiral ganglion had fewer cells. In the control, the long axes of the anterior and posterior semicircular ducts were at right angles to each other and in vertical planes, but in the exencephalics, they tended more laterally towards the horizontal plane. The differentiation of the cristae ampullares and maculae was also severely affected. In several specimens, the entire membranous labyrinth had been distended; these labyrinths also had unusual epithelial infoldings. In cadmium-treated nonexencephalic fetuses, the external ears were normal and appropriate to the body size; five of them were examined histologically; in all, the five middle ear contents were hypoplastic; in three, the cochlea had a maximum of two turns and the organ of Corti, crista ampullaris, and macula were hypoplastic. By an analogy to abnormalities of mutants with neural tube defects, it is suggested that the exencephaly induced by cadmium might affect the differentiation of the ear. Partial involvement of the ear in nonexencephalic experimental embryos may be the result of direct action of cadmium during critical stages of development.

Ultrastructural effects of cadmium on the epididymis of the cryptorchid rat.

The short-term (90 min) effect of an intraperitoneal injection of cadmium chloride (3 mumol/100 g body weight) was studied with the electron microscope in the epididymis of mature rats rendered unilaterally cryptorchid 60 days before injection. It was found that the endothelium of the epididymal capillaries of the cryptorchid organ, at this low dose and short time, showed neither separation of cytoplasmic leaflets, nor platelet damage, nor extravasation, which are the lesions previously described by us and which were present in the contralateral, scrotal epididymis. The possible mechanisms for the protective action of cryptorchidism against the effects of cadmium on capillary endothelia are discussed.

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.

Depression of serum cholinesterase activity by cadmium

Two serum enzymes which originate from the liver under different circumstances were examined as potential biological indicators in serum for cadmium toxicity. The first of those is an enzyme that leaks from damaged liver cells. The second is an enzyme that is secreted by the normal functioning liver. Cadmium chloride was injected s.c. into male and female rats of the Wistar strain (8, 15 and 22 weeks old), at doses of 1.0, 1.5 and 2.0 mg Cd/kg body weight (in total 18 groups). Cholinesterase (CHE; EC 3.1.1.8) activity in serum was found to decrease with time after the administration of a single injection of cadmium chloride and, in all experimental groups, was significantly lower than the control values on day 2 after the injection. Glutamic pyruvic transaminase (GPT; EC 2.6.1.2) activity in serum, however, increased only in the oldest group of males receiving the high dose levels of cadmium. A time-course experiment in which male and female rats 15 weeks of age were administered 1.5 mg Cd/kg body weight showed that the serum CHE activity started to decrease on day 1 after the injection, attained the lowest level on days 2 and 3, and then recovered almost to control levels on day 5. On the other hand, the GPT activity remained at or less than control values throughout the experimental period. The results indicate that CHE activity in serum is a sensitive biological indicator for cadmium toxicity.

Isolation and partial characterization of a cadmium-binding protein from the liver of alligators exposed to cadmium

Seven American alligators, Alligator mississippiensis, were each administered a single, intracardiac injection of cadmium chloride, at a dose of 1.0 mg Cd/kg body wt. At sacrifice, the highest concentration of Cd was found in the liver, bound to a cytosolic protein with characteristics similar to mammalian metallothionein (MT). Gel filtration (Sephadex G-75) of the cytosol revealed a peak containing Cd and to a lesser extent, zinc (Zn), having the same relative elution volume ( V e V o ) as rat hepatic Cd, Zn-MT. Anion-exchange chromatography (DEAE-Sephacel) of material having a V e V o of 1.7–1.9 revealed a major Cd-peak corresponding to rat Cd, Zn-MT(I) and a minor peak corresponding to Cd, Zn-MT(II). Neither peak contained significant amounts of Zn. Heat treatment of alligator hepatic cytosol, followed by selective acetone precipitation, yielded material having a molar Cd : Zn ratio of 9.15:1 compared to 0.67:1 in material purified from Cd-pretreated rat liver. Spectral analysis of the material purified from both sources showed an absorbance peak between 250 and 260 nm and no absorbance peak at 280 nm, characteristic of mammalian MT.

Cadmium-induced alterations in the Siberian hamster epididymis.

The epididymis of sexually mature Siberian hamsters was found to consist of eight histologically distinct zones that were similar, in most respects, to those reported for other species. The notable exception to this is the presence of two types of tubules in zone 6; the typical major tubules predominate but are accompanied by smaller, contiguous, minor tubules. Following a single parenteral injection of cadmium chloride, the testes became necrotic and exhibited generalized sloughing of the seminiferous epithelium. The epididymis, on the other hand, retained their integrity following cadmium administration, although foci of degenerating cells were observed in the more proximal portions of the organ--i.e., zones 1-3. Vacular compromise is believed to be responsible for these necroses because of the severe edematous changes observed in the interstitial spaces. Evidence is presented for the localized degradation and elimination of necrotic cells from the testes as well as the epididymis.

Induction of metallothionein and metallothionein mRNA in rainbow-trout liver following cadmium treatment.

A low-molecular-weight cadmium-binding protein was induced in the livers of rainbow trout (Salmo gairdnerii) following a series of intraperitoneal injections of cadmium chloride. The subsequent purification and amino acid analysis of this protein showed it to be a true metallothionein. As in higher organisms, two major forms of metallothionein appeared to be present in the liver following cadmium treatment. Following a similar induction procedure total RNA was also isolated and shown to contain high levels of metallothionein-mRNA activity when assayed in a wheat-germ cell-free translation system. This activity was present in the Poly-A+-containing fraction of the total RNA. The bulk of this mRNA activity was shown to be in the 8-10S region of a sucrose gradient.

Effect of cadmium chloride on steroidogenic enzymes in the Bidder's organ of the toad (Bufo melanostictus).

Injection of cadmium chloride in a toad increases both the delta 5-3 beta-hydroxy-steroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase activities in Bidder's organ.

Effects of cadmium chloride on ovulation and on induction of sterility in the female golden hamster.

The effects of single subcutaneous injections of cadmium chloride (CdCl2) on ovulation, egg transport and early pregnancy in the golden hamster were studied. While a single dose of 1.25 or 2.5 mg/kg of CdCl2 imposed none to marginal effects, hamsters treated with 5 or 10 mg/kg CdCl2 experienced a period of sterility ranging from 11-69 (5 mg/kg) or 46-71 (10 mg/kg) days, followed by a normal pregnancy. Administration of CdCl2 also induced ovulation inhibition which was dose-and time-dependent. A minimum dose of 5 mg/kg CdCl2 was needed to inhibit ovulation. When CdCl2 was given closer to the time of the luteinizing hormone (LH) surge on the day of proestrus, a more pronounced effect on ovulation was recorded. The incidence of failure of ovulation was associated with decreased progesterone levels in serum and inflammation, hemorrhages and necrosis in the ovary. However, the ovarian lesions lasted less than 4 days. The results indicate that CdCl2 inhibits ovulation when administered close to the time of ovulation, whereas its influence on pregnancy is pronounced but temporary.

Neurotoxic effects of cadmium in young rats

This study examined the effects of cadmium on the brain of male, Sprague-Dawley rats of different ages. Cadmium was more toxic in 4-day-old than in adult rats, thus 2 and 4 mg/kg were given sc to the younger rats and 4 and 6 mg/kg to the older rats. The lower doses resulted in no mortality and the higher dose about 10% mortality in both groups. Four days after a sc injection of cadmium chloride (4 mg Cd/kg) to 4-day-old rats, lesions were evident in the corpus callosum, caudate-putamen, and cerebellum, while 2 mg/kg of cadmium produced only slight cerebellar damage. Nineteen days after injection of 4 mg Cd/kg to 4-day-old rats, a large cystic cavity was evident where the corpus callosum is normally located. In contrast, cadmium did not produce any observable brain damage in adult rats at 4 or 6 mg/kg, either 4 or 19 days after injection. Eighteen days after treatment, hyperactivity was evident in newborn rats exposed to 4 mg/kg of cadmium, but not in newborn rats exposed to 2 mg/kg of cadmium or in adult rats treated with 4 or 6 mg/kg of cadmium. Thus, cadmium at a dose that produces only a few deaths is toxic to the brain of newborn rats, as evident by hyperactivity and lesions.