Xenobiotic toxins

Clearance tests of liver function assess a number of physiologic activities including hepatic uptake, hepatic metabolism, and hepatic excretion. Typical clearance tests of liver function include indocyanine green (ICG), antipyrine clearance test and C aminopyrine breath test. These tests give an estimation of the ability of the liver to extract and detoxify exogenous toxins (xenobiotics). Measuring the excretion of endogenously produced serum bile acids is an additional measure of hepatic clearance and has been used as a sensitive measure of early solvent hepatotoxicity." "... 

Cellular defense mechanisms against toxins (A multistep mechanism for elimination of toxic metabolites and xenobiotics. It involves various transport, oxidation, and conjugation steps.) are usually divided into several steps as it is visualized on Fig. 3. Organic anion transporting proteins (OATPs) are responsible for the cellular uptake of endogenous compounds and... 

As explained in Chapter 1, the toxicity of natural xenobiotics has exerted a selection pressure upon living organisms since very early in evolutionary history. There is abundant evidence of compounds produced by plants and animals that are toxic to species other than their own and which are nsed as chemical warfare agents (Chapter 1). Also, as we have seen, wild animals can develop resistance mechanisms to the toxic componnds prodnced by plants. In Anstralia, for example, some marsupials have developed resistance to natnrally occnrring toxins produced by the plants upon which they feed (see Chapter 1, Section 1.2.2). 

To date, there is very little known about if and how phytochemicals modulate the metabolism of GIT tissues other than the liver. Of particular interest are the xenobiotic metabolizing enzymes of the GIT, which are involved with transformation of drugs and toxins. Whereas the metabolic activities of the resident microflora dominate in the large intestine, mucosal enzyme activities are more important in the small intestine where bacterial densities are lower and the villi and microvilli increase the area of exposure. 

Although the emphasis is on drugs, the same principles apply to any xenobiotic agent. The major difference between drugs and other xenobiotics such as environmental toxins is the dose. The dose of common drugs is usually on the order of 100 mg/day and can be more than a gram a day in contrast, exposure to most other xenobiotics is typically much lower. 

Xenobiotic type - drugs, toxins, carcinogens, mutagens. 

To arrive at the receptor site in the target cell, the blood must transport the absorbed xenobiotic. The time to the onset of toxicity depends on how quickly plasma levels of the toxic compound may be achieved. In contrast, the time to reach peak plasma concentration of the toxin is significantly longer after oral administration. 

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