Cadmium-induced Changes Research Articles

Transcriptional regulation of metal transport genes and mineral nutrition during acclimatization to cadmium and zinc in the Cd/Zn hyperaccumulator, Thlaspi caerulescens (Ganges population)

We investigated changes in mineral nutrient uptake and cellular expression levels for metal transporter genes in the cadmium (Cd)/zinc (Zn) hyperaccumulator, Thlaspi caerulescens during whole plant and leaf ontogenesis under different long-term treatments with Zn and Cd. Quantitative mRNA in situ hybridization (QISH) revealed that transporter gene expression changes not only dependent on metal nutrition/toxicity, but even more so during plant and leaf development. The main mRNA abundances found were: ZNT1, mature leaves of young plants; ZNT5, young leaves of young plants; MTP1 (= ZTP1 = ZAT), young leaves of both young and mature plants. Surprisingly different cellular expression patterns were found for ZNT1 and ZNT5, both belonging to the ZIP family of transition metal transporters: ZNT1, photosynthetic mesophyll and bundle sheath cells; ZNT5, nonphotosynthetic epidermal metal storage cells and bundle sheath cells. Thus, ZNT1 may function in micronutrient nutrition while ZNT5 may be involved in metal storage associated with hyperaccumulation. Cadmium inhibited the uptake of Zn, iron (Fe) and manganese (Mn), probably by competing for transporters or by interfering with the regulation of transporter gene expression. Cadmium-induced changes in cellular expression for ZNT1, ZNT5 and MTP1 could also be part of plant acclimatization to Cd toxicity. Defence against Cd toxicity involved enhanced uptake of magnesium (Mg), calcium (Ca) and sulphur (S).

Effects of Aqueous Extract of Schizandra Chinensis Fruit on Cadmium-Induced Change of Monoamine Neurotransmitters in Rats.

The effects of aqueous extract of Schizandra Chinensis Fruit (AESC) on cadmium-induced changes of monoamine neurotransmitters in the different brain regions of adult rats were investigated. Male rats were received intraperitoneal (i.p.) administration of CdCl2 (0.6 mg/kg/d) for 21 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA) in striatum and serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in cortex were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Cd intoxicated rats (P < 0.05), while pretreatment with AESC (20 mg/kg/d or 60 mg/kg/d, p.o., 30 min before CdCl2) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC significantly increased the reduction of glutathione contents and superoxide dismutase activities in cortex induced by CdCl2. These results suggest that AESC ameliorates Cd-induced depletion of monoamine neu-rotransmitters in brain through its antioxidant activity.

On the mechanisms of cadmium stress alleviation in Medicago truncatula by arbuscular mycorrhizal symbiosis: A root proteomic study

The arbuscular mycorrhizal (AM) symbiosis belongs to the strategies plants have developed to cope with adverse environmental conditions including contamination by heavy metals such as cadmium (Cd). In the present work, we report on the protective effect conferred by AM symbiosis to the model legume Medicago truncatula grown in presence of Cd, and on the 2-D-based proteomic approach further used to compare the proteomes of M. truncatula roots either colonised or not with the AM fungus Glomus intraradices in Cd-free and Cd-contaminated substrates. The results indicated that at the proteome level, 9 out of the 15 cadmium-induced changes in nonmycorrhizal roots were absent or inverse in those Cd-treated and colonized by G. intraradices, including the G. intraradices-dependent down-accumulation of Cd stress-responsive proteins. Out of the twenty-six mycorrhiza-related proteins that were identified, only six displayed changes in abundance upon Cd exposure, suggesting that part of the symbiotic program, which displays low sensitivity to Cd, may be recruited to counteract Cd toxicity through the mycorrhiza-dependent synthesis of proteins having functions putatively involved in alleviating oxidative damages, including a cyclophilin, a guanine nucleotide-binding protein, an ubiquitin carboxyl-terminal hydrolase, a thiazole biosynthetic enzyme, an annexin, a glutathione S-transferase (GST)-like protein, and a S-adenosylmethionine (SAM) synthase.

Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to assess the possible protective roles of onion ( Allium cepa Linn) and garlic ( Allium sativum Linn) extracts on Cd-induced testicular damage and spermiotoxicity. The control group received double distilled water; Cd group received Cd (1.5 mg/100 g BW/day) orally; extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g BW/day) orally for one week and then simultaneously challenged with Cd (1.5 mg/100 g BW/day) for additional three weeks. Testicular tissue oxidant/antioxidant status and sperm characteristics were determined. Cd caused a marked ( p < 0.001) rise in testicular lipid peroxidation (LPO) and glutathione S-transferase (GST) levels whereas glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and alkaline phosphatase (ALP) levels were decreased. Cd intoxication significantly ( p < 0.001) decreased epididymal sperm concentration and sperm progress motility, increased percent total sperm abnormalities and live/dead count. Both extracts successfully attenuated these adverse effects of Cd. Onion extract offers a dose-dependent protection. Our study demonstrated that aqueous extracts of onion and garlic could proffer a measure of protection against Cd-induced testicular oxidative damage and spermiotoxicity by possibly reducing lipid peroxidation and increasing the antioxidant defence mechanism in rats.

Cadmium-induced changes in the membrane lipid composition of maize plants

The effect of 10, 25 and 50 μM Cd(NO 3 ) 2 on the fatty acid composition was investigated in young maize seedlings ( Zea mays L., hybrid Norma). After 7 days’ exposure to cadmium slight changes were observed in the fatty acid composition, which were more pronounced in the roots than in the leaves. In the leaves cadmium did not affect the lipid composition of the monogalactosyldiacylglycerol (MGDG) or digalactosyldiacylglycerol (DGDG) fractions, while in the phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) fractions there was a decrease in the proportion of hexadecanoic acid (16:0) and an increase in the level of linoleic acid (18:2) and linolenic acid (18:3). The proportion of trans -Δ3-hexadecanoic acid in leaf PG also decreased. In the roots significant changes were observed in all the fractions examined after Cd stress. In the MGDG the level of stearic acid (18:0) and oleic acid (18:1) decreased, but that of 18:2 and 18:3 increased. In the case of PE the amount of 16:0 decreased, while that ...

Cadmium-induced changes in Per 1 and Per 2 gene expression in rat hypothalamus and anterior pituitary: Effect of melatonin

Chronic cadmium (Cd) administration affects the circadian release of pituitary hormones in rats. To assess whether Cd modifies expression of two major clock genes, period (Per) 1 and Per 2, in the hypothalamic–pituitary unit and to what extent the changes could be prevented by melatonin, rats were exposed to CdCl 2 (5 ppm in drinking water) with or without melatonin (3 μg/mL drinking water) for 1 month and were killed at two time intervals, i.e. a the beginning of the rest span (09:00 h) and at the middle of the activity span (01:00 h). Hypothalamic and pituitary mRNA levels encoding Per 1 and Per 2 were measured by real-time PCR analysis. Cd treatment decreased expression of hypothalamic Per 1 gene at both time intervals, of hypothalamic Per 2 gene at 01:00 h, and of adenohypophysial Per 1 and Per 2 genes at 09:00 h. Melatonin administration counteracted most of the effects of Cd and augmented hypothalamic Per 2, and adenohypophysial Per 1 and Per 2 gene expression. The results indicate that Cd administered chronically in the drinking water to rats affected expression of clock genes in the hypothalamic–pituitary unit, an effect prevented by melatonin.

Effect of cadmium on the phenolic compounds formation in the callus cultures derived from various organs of the tea plant

The effects of cadmium (6.3 × 10−5 M or 10.6 × 10−5 M) on the growth of tea plant (Camellia sinensis L.) callus cultures derived from leaves, stems, and roots and on the formation, in these cultures, of phenolic compounds, including flavans and lignin, which are characteristic of the tea plant, were investigated. In the calli derived from leaves and stems, cadmium treatment decreased the biomass increment, while in the calli derived from roots, growth characteristics remained at the control level. Under the effect of cadmium, the content of phenolic compounds, including flavans, in the leaf calli decreased, while in the stem and root calli, it either increased (at the cadmium concentration of 6.3 × 10−5 M), or was close to a control one (at the cadmium concentration of 10.6 × 10−5 M). The lignin content in the root and stem calli increased, but it did not change in the leaf calli. All this data demonstrate that the cadmium-induced changes in phenolic metabolism of the tea plant callus culture depended both on the cadmium concentration in the medium and on the origin of calli.

Physiologic Regulation of a Tetrodotoxin-Sensitive Sodium Influx That Mediates a Slow Afterdepolarization Potential in Gonadotropin-Releasing Hormone Neurons: Possible Implications for the Central Regulation of Fertility

The brain controls fertility through release of gonadotropin-releasing hormone (GnRH), but the mechanisms underlying action potential patterning and GnRH release are not understood. We investigated whether GnRH neurons exhibit afterdepolarizing potentials (ADPs) and whether these are modified by reproductive state. Whole-cell current-clamp recordings of GnRH neurons in brain slices from ovariectomized mice revealed a slow ADP (sADP) after action potentials generated by brief current injection. Generating two or four spikes enhanced sADP amplitude and duration. sADP amplitude was not affected by blocking selected neurotransmitter/neuromodulator receptors, delayed-rectifier potassium channels, calcium-dependent cation channels, or hyperpolarization-activated cation channels but was halved by the calcium channel blocker cadmium and abolished by tetrodotoxin. Cadmium also reduced peak latency. Intrinsic mechanisms underlying the sADP were investigated using voltage-clamp protocols simulating action potential waveforms. A single action potential produced an inward current, which increased after double and quadruple stimulation. Cadmium did not affect current amplitude but reduced peak latency. Pretreatment with blockers of calcium-activated potassium currents (I(KCa)) reproduced this shift and blocked subsequent cadmium-induced changes, suggesting cadmium changes latency indirectly by blocking I(KCa). Tetrodotoxin abolished the inward current, suggesting that it is carried by sodium. In contrast, I(KCa) blockers increased the inward current, indicating that I(KCa) may oppose generation of the sADP. Strong sADPs were suprathreshold, generating repetitive spontaneous firing. I(ADP), sADP, and excitability were enhanced by in vivo estradiol, which triggers a preovulatory surge of GnRH release. Physiological feedback modification of this inward current and resulting sADP may modulate action potential firing and subsequent GnRH release.

Stage-dependency of apoptosis and the blood-testis barrier in the dogfish shark (Squalus acanthias): cadmium-induced changes as assessed by vital fluorescence techniques

Naturally occurring heavy metals and synthetic compounds are potentially harmful for testicular function but evidence linking heavy metal exposure to reduced semen parameters is inconclusive. Elucidation of the exact stage at which the toxicant interferes with spermatogenesis is difficult because the various germ cell stages may have different sensitivities to any given toxicant, germ cell development is influenced by supporting testicular somatic cells and the presence of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as Squalus acanthias provide a suitable model for studying aspects of vertebrate spermatogenosis because of their unique features: spermatogenesis takes place within spermatocysts and relies mainly on Sertoli cells for somatic cell support; spermatocysts are linearly arranged in a maturational order across the diameter of the elongated testis; spermatocysts containing germ cells at different stages of development are topographically separated, resulting in visible zonation in testicular cross sections. We have used the vital dye acridine orange and a novel fluorescence staining technique to study this model to determine (1) the efficacy of these methods in assays of apoptosis and blood-testis barrier function, (2) the sensitivity of the various spermatogonial generations in Squalus to cadmium (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect more mature spermatogenic stages and other physiological processes in the testis. Our results show that cadmium targets early spermatogenic stages, where it specifically activates a cell death program in susceptible (mature) spermatogonial clones, and negatively affects blood-testis barrier function. Since other parameters are relatively unaffected by cadmium, the effects of this toxicant on apoptosis are presumably process-specific and not attributable to general toxicity.

Cadmium-induced changes in pigments, total phenolics, and phenylalanine ammonia-lyase activity in fronds ofAzolla imbricata

This study was designed to examine the effects of cadmium on several color-related parameters (including chlorophyll, carotenoid, and anthocyanin), total phenolics, and phenylalanine ammonia-lyase (PAL) activity in an aquatic fern species Azolla imbricate (A. imbricata). Cd accumulation and effects in the fronds were closely related with Cd concentration in the growth medium. The fronds under 0.5 mg/L Cd treatment turned red on the 3rd day, and this color change also appeared under 0.05 and 0.1 mg/L Cd treatment on the 5th day. Correlated with the color change, the contents of chlorophyll and carotenoid in the fronds significantly decreased in the presence of high Cd concentrations, while the anthocyanin content increased during the experiment. Significant increase in total phenolics content and PAL activity were also detected during Cd treatment. The results suggested that the Cd-induced change in color of fronds might be due to the decrease in chlorophyll and carotenoid and the increase in anthocyanin. Anthocyanin, total phenolics and their biosynthesis-related PAL might play a role in detoxification of Cd in A. imbricata.

Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium

Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK-specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat-shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells.

Cadmium-induced changes in antioxidative systems, hydrogen peroxide content, and lipid peroxidation inArabidopsis thaliana

To study the relationship between cadmium (Cd)-induced phytotoxicity and oxidative stress, we grew Cd-sensitive wild-type (WT) and Cd-resistant type (RT) seedlings ofArabidopsis thaliana on MS media containing up to 500 μM CdCl2. The resistant seedlings showed higher biomasses and lower hydrogen peroxide and lipid peroxidation levels, the latter expressed in terms of malondialdehyde (MDA) production. These results indicate that RT plants experience lower oxidative stress when exposed to Cd. Furthermore, compared with the WT, RT seedlings have significantly higher activities of superoxide dismutase (SOD) and enzymes related to hydrogen peroxide removal, e.g., guaiacol peroxidase (GPX), ascorbate peroxidase (APX), and glutathione reductase (GR). These differential responses suggest that such phytotoxicity could be induced by oxidative stress, and that lower accumulations of hydrogen peroxide confer Cd tolerance in seedlings.

Role of sulphur availability on cadmium-induced changes of nitrogen and sulphur metabolism in maize ( Zea mays L.) leaves

The interactions between sulphur nutrition and Cd exposure were investigated in maize ( Zea mays L.) plants. Plants were grown for 12 days in nutrient solution with or without sulphate. Half of the plants of each treatment were then supplied with 100 μM Cd. Leaves were collected 0, 1, 2, 3, 4 and 5 days from the beginning of Cd application and used for chemical analysis and enzyme assays. Cd exposure produced symptoms of toxicity (leaf chlorosis, growth reduction) and induced a noticeable accumulation of non-protein SH compounds. As phytochelatins are glutamate- and cysteine-rich peptides, the effect of cadmium on some enzyme activities involved in N and S metabolism of maize leaves was studied in relation to the plant sulphur supply. In vivo Cd application to S-sufficient plants resulted in a drop of all measured enzyme activities. On the other hand, S-deficient plants showed a decrease in nitrate reductase (NR; EC 1.6.6.1) and glutamine synthetase (GS; EC 6.3.1.2) activity, and an increase in NAD-dependent glutamate dehydrogenase (GDH; EC 1.4.1.2) and phosphoenolpyruvate carboxylase (PEPc; EC 4.1.1.31) activity as a result of the Cd treatment. Furthermore, in the same plants ATP sulphurylase (ATPs; EC 2.7.7.4) and O-acetylserine sulphydrylase (OASs; EC 4.2.99.8) showed a particular pattern as both enzymes exhibited a transient maximum value of activity after 4 days from the beginning of Cd exposure. Results provide evidence that the increase of ATPs, OASs, GDH and PEPc activities, observed exclusively in S-deficient Cd-treated plants, may be part of the defence mechanism based on the production of phytochelatins.

Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene

Cadmium is a well-known human carcinogen and a potent nephrotoxin. Lipid peroxidation is involved in cadmium-related toxicity. Vitamin E and β-carotene are effective antioxidants and free radical scavengers. Therefore, the present study was carried out to investigate the potential protective effects of vitamin E and β-carotene alone or in combination against cadmium (Cd) toxicity. Cadmium chloride (CdCl2, 5 mg/kg BW, 1/15 LD50), vitamin E (100 mg/kg BW), β-carotene (10 mg/kg BW), and vitamin E with β-carotene (100+10 mg/kg BW, respectively) were orally administered by gavage alone or in combination. The tested doses were given to rats every other day (15 times). Results obtained showed that CdCl2 significantly (P<0.05) induced free radicals in plasma, liver and brain. The activities of glutathione S-transferase (GST) (plasma and liver), alkaline phosphatase (AlP) (plasma and liver), aspartate aminotransferase (AST), alanine aminotransferase (ALT) (liver) and acetylcholinesterase (AChE) (plasma and brain) were significantly (P<0.05) decreased due to CdCl2 administration, whereas, the activities of AST and ALT were increased in plasma. Treatment with CdCl2 caused a significant (P<0.05) increase in glucose, urea, creatinine and bilirubin in plasma. On the other hand, results showed that CdCl2 significantly (P<0.05) decreased plasma total protein (TP), albumin (A), blood hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), while total leukocyte count (TLC) increased. Treatment with CdCl2 caused a significant (P<0.05) decrease in sperm concentration, motility (%), weight of testes and epididymis, and increase in dead and abnormal sperm. Results demonstrated the beneficial influences of vitamin E, β-carotene alone and/or in combination in reducing the harmful effects of CdCl2.

Cadmium-induced changes in the membrane of human erythrocytes and molecular models

Cadmium-induced changes in the membrane of human erythrocytes and molecular models

Cadmium-induced changes in antioxidant enzymes in suspension culture of soybean cells.

Cadmium (Cd), similarly to other heavy metals, inhibits plant growth. We have recently showed that Cd(2+) either stimulates (1-4 microM) or inhibits (>or= 6 microM) growth of soybean (Glycine max L.) cells in suspension culture (Sobkowiak & Deckert, 2003, Plant Physiol Biochem. 41: 767-72). Here, soybean cell suspension cultures were treated with various concentrations of Cd(2+) (1-10 microM) and the following enzymes were analyzed by native electrophoresis: superoxide dismutase (SOD), catalase (CAT), peroxidase (POX) and ascorbate peroxidase (APOX). We found a significant correlation between the cadmium-induced changes of soybean cell culture growth and the isoenzyme pattern of the antioxidant enzymes. The results suggest that inhibition of growth and modification of antioxidant defense reactions appear in soybean cells when Cd(2+) concentration in culture medium increases only slightly, from 4 to 6 microM.

Cadmium-induced changes in antioxidant enzymes in suspension culture of soybean cells.

Cadmium (Cd), similarly to other heavy metals, inhibits plant growth. We have recently showed that Cd(2+) either stimulates (1-4 microM) or inhibits (&gt;or= 6 microM) growth of soybean (Glycine max L.) cells in suspension culture (Sobkowiak &amp; Deckert, 2003, Plant Physiol Biochem. 41: 767-72). Here, soybean cell suspension cultures were treated with various concentrations of Cd(2+) (1-10 microM) and the following enzymes were analyzed by native electrophoresis: superoxide dismutase (SOD), catalase (CAT), peroxidase (POX) and ascorbate peroxidase (APOX). We found a significant correlation between the cadmium-induced changes of soybean cell culture growth and the isoenzyme pattern of the antioxidant enzymes. The results suggest that inhibition of growth and modification of antioxidant defense reactions appear in soybean cells when Cd(2+) concentration in culture medium increases only slightly, from 4 to 6 microM.

Cadmium-induced changes in the membrane of human erythrocytes and molecular models

The structural effects of cadmium on cell membranes were studied through the interaction of Cd 2+ ions with human erythrocytes and their isolated unsealed membranes (IUM). Studies were carried out by scanning electron microscopy and fluorescence spectroscopy, respectively. Cd 2+ induced shape changes in erythrocytes, which took the form of echinocytes. According to the bilayer couple hypothesis, this result meant that Cd 2+ ions located in the outer monolayer of the erythrocyte membrane. Fluorescence spectroscopy measurements in IUM indicated a disordering effect at both the polar headgroup and the acyl chain packing arrangements of the membrane phospholipid bilayer. Cd 2+ ions also interacted with molecular models of the erythrocyte membrane consisting in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representing classes of phospholipids located in the outer and inner monolayers the erythrocyte membrane, respectively. X-ray diffraction indicated that Cd 2+ ions induced structural perturbation of the polar headgroup and of the hydrophobic acyl regions of DMPC, while the effects of cadmium on DMPE bilayers were much milder. This conclusion is supported by fluorescence spectroscopy measurements on DMPC large unilamellar vesicles (LUV). All these findings point to the important role of phospholipid bilayers in the interaction of cadmium on cell membranes.

Cadmium-Induced Changes in Chloroplast Lipids and Photosystem Activities in Barley Plants

Fatty acid content and composition of chloroplast membranes, ethylene production associated with thylakoid lipids degradation as well as photosynthetic electron transport involving photosystems 1 and 2 were used to determine the effects of increasing Cd concentrations in the growth medium [0, 14, 28, and 42 mg (Cd) kg-1(sand)] on the photosynthetic performance of barley plants (H. vulgare L., cv. CE9704). High concentrations of Cd triggered serious disturbances of the chloroplast membranes. Ethylene production increased whereas a drop of 18:3 fatty acid content occurred, indicating that Cd mediates lipid peroxidation in the thylakoids. The enhanced ethylene production could be used as an early indicator of Cd-induced membrane degradation, yet at very high concentration (42 mg kg-1) Cd decreased ethylene production.

Cadmium-induced changes in apoptotic gene expression levels and DNA damage in mouse embryos are blocked by zinc.

Cadmium is a potent teratogen in laboratory animals, causing exencephaly when administered at early stages of development. Due to its heterogenicity with respect to molecular targets, the mechanisms behind cadmium toxicity are not well understood. In the present study, C57BL/6 pregnant mice were treated with saline, cadmium, or zinc plus cadmium at 8 days post-coitus and studied 24 h after exposure. Cadmium induced significant DNA damage in the embryonic cells. Cadmium also induced embryonic growth retardation, as well as a significant upregulation of p53, p21, and Bax transcription levels. At the same time, there was a downregulation of Bcl-2, shifting the equilibrium Bcl-2/Bax toward the apoptotic pathway. There was an increase in apoptotically stained cells in the cadmium-treated embryos, and pro-caspase-3 was significantly activated. Zinc pretreatment maintained DNA damage at the control levels. It also prevented cadmium-induced effects on the expression levels of p53 and p21. The cadmium-induced decrease in Bcl-2 was inhibited, whereas the Bax levels were maintained closer to the control values. The Bad transcripts did not change at any experimental condition. Morphologically, zinc could maintain the embryological development, where apoptotic areas were as in the controls, and decrease por-caspase-3 activation. In summary, cadmium administered to pregnant mice increased primary DNA damage and activated the apoptotic pathway. These effects could be ameliorated by zinc pretreatment, and, because of that, it is possible that the mechanisms of cadmium-induced teratogenicity are related to zinc metabolism.