Mode of Action of Cadmium Poisoning – Explained!

Because of its known toxicity to animals, a large amount of research has been carried out to find out how and why this metal is poisonous. For this reason, this will be largely devoted to cadmium.

For comparative purposes, reference will also be made to other toxic metals. It is hoped, however, that by presenting the information discovered about cadmium, the reader will be able to see ways in which similar approaches could be used to examine the effects of other metals.

Cadmium enters the body through diet and by breathing air containing dust particles which themselves contain cadmium. It is a surprising finding that less than 3 percent of the cadmium in the diet is taken up by the body.

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This is due to a remarkable ability of the intestine to avoid absorbing this metal. The situation in the lungs, however, is quite different-here about 30 percent of the inhaled cadmium is taken up by the body. This, at once, suggests that in the case of this metal, air pollution is far more dangerous than water pollution.

Once taken up by the body, the cadmium at first circulates in the blood. The blood, however, soon interacts with two important organs, the liver and the kidneys. The cells of these organs respond to the presence of cadmium by producing a protein which binds the metal.

After this, the metal is not free in solution but trapped inside the cells. This is because the protein cannot diffuse out of the cells. The protein, called thiamine, is unusual, in that it contains much more sulphur than ordinary cell proteins.

When combined with a metal, it is called metallothionine. It seems that the same protein can combine with metals other than cadmium too. Zinc, for example, combines with a protein which can also bind cadmium.

The presence of these protein molecules in the liver and kidney means that the cadmium inside the body is not easily excreted. In humans, this amounts to a very serious condition-accumulation.

It is believed that over 20 or 30 years, very small traces of cad­mium in the environment can gradually build up in the liver and the kidney tissue until finally the protein binding mechanism can no longer provide any protection.

At this point, the first signs of illness begin to show up as other parts of the body become affected. The arterial portion of the blood circulation undergoes certain changes, which results in an increase in blood pressure.

This is called hypertension. The chemistry of the blood itself gets altered. The concentration of glucose becomes higher. This has been proved in the experiments with mammals in the laboratory.

It has even been reported in marine organisms which live in a cadmium contaminated environment. Returning to humans, it has been found that cadmium poisoning is also associated with abnormalities in bone structure due to some interference with the proper deposition of calcium in the bones.

It is important at this point to mention that in Japan (where cadmium poisoning was studied in great detail) it was mainly women who showed the symptoms. Most of these women were over 40 years old and had several children.

The reason for this is that pregnancy places an additional strain on the calcium metabolism of the body. Thus, as a woman becomes older, she accumulates more and more cadmium and pregnancy results in symptoms which otherwise might be absent or much less serious.

The presence of cadmium in organs and tissues is usually detected by atomic absorp­tion spectroscopy. This is a time-consuming method and usually involves careful digestion of the tissue samples in strong acid.

In competent hands, this method can reliably measure cadmium at concentrations as low as 0.05 ppm. The equipment for the atomic absorption technique is very expensive and requires a skilled operator.

It is, therefore, important to find out that cadmium can also be measured by a colorimetric method, needing only a spectro­photometer to take the final measurements. Such a method is the Dithizone method which has been used successfully for cadmium measurements on marine organisms. It remains a useful technique where atomic-absorption equipment is not available.

Much research has been carried out on the effects of cadmium within living cells. It has been found that it is potentially capable of affecting many processes in cells, simply by inactivating enzymes. The disturbance to the glucose level in the blood is possibly due to the reverse effect, the stimulation of certain enzymes.

For example, some evidence has been obtained, which suggests that four enzymes which control the synthesis of glucose (by gluconeogenesis) increase their activity in the presence of cadmium.

The cells obtain their energy by the combined effects of glycolysis (glucose break­down) and aerobic respiration in the particles, called mitochondria.

Both of these processes could be inhibited by cadmium. Research in this field is hampered by the fact that in order to study the processes, the cells must first be broken up.

When cadmium is added to such a system, we are dealing with artificial situation, which might not apply to the whole cell condition. For example, the protein binding mechanism may operate effectively when whole cells are exposed to cadmium.

In spite of these difficulties, evidence is being gathered which shows that respiring mitochondria are less efficient in making ATP when cadmium is added to the preparation whether this accurately reflects the situation in the cadmium-poisoned animal remains to be seen.

Perhaps, the more promising approach is to measure the important biochemical pro­cesses in tissues of known cadmium content, which have been taken from animals which have been feeding on a low cadmium diet.

These would contain enough cadmium to produce poisoning symptoms after several weeks. Results obtained, using this approach, are more likely to provide information which applies in a real life situation.

Much has been learned about the cadmium-binding protein itself. The procedure here is to homogenize the tissue and, then, subject them to differential centrifugation, the tissue fragments being dispersed in a suitable solution such as isotonic saline.

The various frac­tions are separated and the final supernatant, after the high speed centrifugation, is usually found to contain the most cadmium. This technique is best used with radioactive cadmium (¹⁰⁹Cd). When the final supernatant is treated with a protein precipitant, such as trichloracetic acid, then centrifuged, it is usually found that most of the radioactivity is in the precipitant.

If instead of precipitating the protein, we subject it to gel filtration, much more informa­tion can be obtained. In this method, the protein solution is allowed to slowly pass down a column of a substance like sephadex G-75.

The mixture of protein is, thus, separated on the basis of molecular weight. The results of this type of research show that the cadmium is bound by one or two protein with a molecular weight near 10,000.

The radioactive tracer technique has shown that marine animals, which have previously encountered cadmium in their environment, have a different cadmium binding capacity when
compared with similar animals from a cadmium-free environment.

Another advantage of this method is that it lends itself well to autoradiography, a procedure by which a thin slice of tissue is placed in contact with a photographic in the dark.

After a period of, exposure the film is developed and the site of location of cadmium, within the tissue, is revealed by dark areas in the film.

This technique requires practice and can be applied at the microscope level for proteins of tissue. For small organisms, the whole animal can be sectioned.

Most of the approaches and techniques described here can be equally applied to other heavy metals or even pesticides. In the latter case, a protective device is needed before using radioisotopes.

Plants differ in one important respect from animals, in that their heavy metal burden may be in the form of external contamination such as in dust on leaves. This may have very little effect on the plants.

Damage to foliage doses, of course, take place and, here, we have a situation which is complicated by the coexistence of photosynthesis, respiration and active transport processes, all of which are interdependent to some extent. Plants have a remarkable ability to avoid taking up many toxic heavy metals from the soil. On the other hand, many multi-cellular and unicellular aquatic plants actually concentrate these substances.

In the case of unicellular plants, laboratory experiments are carried out to find out their tolerance levels. Their ability to take up metals is best studied by the radioactive method because, unlike the case with animals, experiments have to be conducted in a short time.

Again, with unicellular plants, the rate of photosynthesis and respiration can be measured, using an oxygen electrode method as described for B.O.D.

The effect of adding controlled amounts of the heavy metal in solution can be observed and the amount required to inhibit or stop respiration for photosynthesis can be determined. This type of approach, using unicellular plants, bypasses the transport mechanisms which would complicate the interpretation of experiments using multi-cellular higher plants.

Research with multi-cellular land plants is still possible but is made more difficult be­cause of the many interacting systems. The metabolism of plants is very much dependent on photosynthesis. To study this process in land plants requires equipment which can reliably monitor the gas exchange with the atmosphere.

The special knowledge and equipment re­quired to do this result in fewer experiments being carried out at any one time. If the metabolic effects of heavy metals on plants are disregarded, then much useful research remains to be carried out for finding the binding sites for these metals in those plants which actively take them up. This is the topic of increasing importance because plants of this type may be used to remove toxic metals from effluents.

The relevant pollutant for important industries, which indicate average values of different parameters. Some of the parameters indicated do not have any direct effect on living system, for example, BOD, which is so frequently mentioned.

Biochemical Oxygen Demand (BOD) quantitatively measures the organic load on the receiv­ing stream and very often, when an effluent with high BOD content is discharged into a river system, fishes in large numbers are found dead, due to lack of dissolved oxygen which is utilized in bio-degradation of organic matter.

Similarly, suspended solids do not have any direct effect but these are considered as carriers for microbes and consequently help in spreading of water borne diseases.