Encyclopedia of Environmental Science and Engineering, Volume I and II

1012 POLLUTION EFFECTS ON FISH

they have much less plasma protein. Compounds that have

a high tendency to bind to plasma proteins may compete

or displace one another from binding sites when they exist

together in the blood. This may be the mechanism of danger-

ous toxic interactions because plasma protein binding sites

become so saturated that a greater percentage of unbound

toxicant exists in the blood than would normally be present

with only one toxicant. When the degree of plasma binding

is high and the rate of release is low, plasma proteins can act

as a storage depot for the bound substances. Storage depots

also frequently result from a particular affinity a toxicant

may possess for certain organs or tissues. Examples of this

are the chlorinated hydrocarbon pesticides which are stores

in body fat and heavy metals such as copper and mercury

which are stored in the liver and kidney of fish (Life, 1969).

Many foreign compounds are capable of producing a

specific effect, that is, are selectivity toxic, on a specific bio-

logical system or systems. These systems are said to be the

site of locus of action of the chemical. The site may be con-

fined to one anatomic location within the animal, or may be

diffusely located throughout the animal. Two fundamental

types of mechanisms are responsible for the selective action

of chemicals on cells or cellular mechanisms.

The first type is a result of factors that increase the con-

centration of the toxicant at specific cell or tissue sites. This

is accomplished in the organisms by mechanisms of selec-

tive translocation and biotransformation. One good example

is the renal tubular (kidney cell) injury produced in fish

exposed to copper. Because copper is excreted by the kidney

it accumulates at tubular cells. As the concentration rises

injurious levels are reached and these cells are damaged or

destroyed (Life, 1969).

A second mechanism in the selective toxicity of chemicals

on cells involves the presence of specific targets or receptor

systems in exposed cells. In this case, the concentration of

the toxicant is the same for all cells, but only certain cells are

affected. This is due to the specificity of action of the toxi-

cant on receptors that are normally occupied by endogenous

hormonal or neurohormonal substances. Organophosphorus

compounds such as parathion and malathion are good exam-

ples of selectively toxic agents that act in this way. These

cholinesterase inhibitors act to inhibit the enzyme respon-

sible for hydrolysis of the neurotransmitter, acetylcholine. In

this example cholinesterase is considered to be the receptor.

Prevention of the hydrolysis of acetylcholine results in the

continuous stimulation of post-synaptic sites throughout the

central and peripheral nervous systems and rapid death due

to respiratory paralysis is the usual outcome.

Biotransformation and Excretion of the Toxicant

The duration and intensity of injurious action of many for-

eign compounds are largely determined by the degree and

speed at which an organism can eliminate these compounds

(Conney, 1967). The kidneys of both marine and fresh water

fishes have been shown to share with mammalian kidneys

the primary role of ridding an animal of potentially toxic

compounds (Forster, 1961, 1967).

The excretion of substances by the kidney is largely

determined by lipid solubility characteristics of the com-

pounds as they enter renal tubules. Molecules with a high

degree of lipid solubility are readily re-absorbed from the

renal tubule through lipoidal membranes back into the cir-

culating blood and consequently are not excreted. It is only

through certain specific biochemical transformations of these

foreign compounds by the organism itself that lipid solubili-

ties are altered and tubular excretion is successful (Brodie

and Erdos, 1962). These reactions or transformations can be

classified as oxidations, reductions, hydrolyses and synthe-

ses (conjugation).

Most animals, including fish, transform (metabolize)

foreign compounds in two successive phases, the first phase

consisting of a variety of oxidations, reductions, and hydro-

lyses and the second phase of a limited number of synthe-

ses or conjugations (Williams, 1967). Phase I reactions can

result in:

1) The inactivation of a toxic compound;

2) The conversion of an initially inactive compound

into a toxic compound; and

3) The conversion of a toxic compound into another

toxic compound.

The second phase of biotransformation, consisting of

synthetic reactions, most often results in the conversion of

toxic compounds into inactive excretory products. This con-

cept of the metabolism of foreign compounds can be repre-

sented as in Figure 2 (Williams, 1967).

Biochemical reactions of both phases of metabolism

are catalyzed by enzymes located in various organ systems,

and it is from the study of the qualitative and quantitative

variations in these enzymes that an evaluation of detoxifying

capacities can be made for an organism (Williams, 1967).

Phase I reactions are carried out by enzymes of normal

metabolic routes and by enzymes which occur in the smooth

endoplasmic reticulum of liver cells. When these cells are

ruptured in the laboratory by homogenization the endoplas-

mic reticulum undergoes fragmentation. High-speed cen-

trifugation separates these fragments from the remaining

cell constituents. These fragments are referred to as micro-

somes and it is the microsomal enzymes that are involved

in the metabolism of many drugs and foreign compounds.

Microsomal enzymes do not generally act on lipid-insoluble

compounds but rather convert lipid-soluble materials by oxi-

dative and reductive processes to less lipid-soluble metabo-

lites, which are more polar substances and, therefore, readily

Phase I

Drug

Activation or

inactivation

Oxidation

reduction

and/or

Hydrolysis

products

Phase II

Inactivation

Synthetic or

conjugation

products

FIGURE 2

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