Reasearch Topics > Toxicity studies > Biochemical biomarkers and cytotoxicity

Biochemical responses are the first line of defense in the cell following exposure to chemicals. Since biochemical responses occur at one of the lowest level of biological organization, the responses are extremely sensitive to toxicant exposure and also are extremely variable among individuals in a given population.

We selected some well established biochemical biomarkers capable of giving a general indication of biological stress due to pollution. These are: acetylcholinesteraseis (AChE), glutathione S-transferases (GST), superoxide dismutases (SOD), glutathione peroxidases (GPx) and glutathione reductase (GPx).

Acetylcholinesteraseis (AChE), a target of organophosphorous (OP) and carbamate insecticides and is a well-stablished specific biomarker of exposure to these agrochemicals. When cholinesterases are inactivated by binding of OPs, an accumulation of ACh occurs at the nerve synapse, interfering with the normal nervous system function.

Glutathione S-transferases (GSTs ) are a family of essential proteins having biosynthetic and detoxication functions in phase II detoxification. Phase II enzymes catalyze the conjugation of various endogenous (sex steroids) and exogenous (many pollutants) substrates with several highly hydrophilic compounds that occur at high levels in cells. The purpose of these reactions is to increase the water solubility of the substrate and thereby facilitate its excretion. In environmental studies the GST is used as a biomarker of exposure to xsenobiotics, which are detoxified by phase II enzymes (azo dyes, PAHs, some organohalogen compounds, many organic epoxids).

Superoxide dismutases (SOD), glutathione peroxidases (GRx) and glutathione reductase (GPx) are enzymatic antioxidants. Antioxidant defense system occur in all aerobic organisms in order to defend cells from the deleterious effects of reactive oxygen species (ROS) that arise naturally or antropogenicaly. Oxidative stress refers broadly to the deleterious effects of ROS that occur when the production of ROS overhelms endogenous antioxidant defense systems of cells. There been considerable interest in the use of responses associated with oxidative stress as a biomarker of environmental contamination. In contrast to other biomarkers (AChE) there is no single measure that by itself confirms the occurrence of oxidative stress or prestress adaptation. However, many potential measures of adaptive responses (increases of antioxidant defense system components) and deleterious responses (oxidations of DNA, lipids and proteins) exist.

All AChE, GTS and antioxidant enzymes indicate exposure of the organism to chemicals, but do not give information of the degree of adverse effect that these changes cause. One of earliest toxic effects of pollutants involve alteration of plasma membrane and the activity of the different intracellular compartments.

 

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Last updated: 10.08.2003