Cellular responses, to toxic compounds

Moller A et al. Two-dimensional gel electrophoresis a powerful method to elucidate cellular responses to toxic compounds. Toxicology 2001 160 129-138. 

The accumulation of fat is a common cellular response to toxic compounds, which is normally reversible. Usually triglycerides accumulate, although sometimes phospholipids accumulate, as occurs after exposure to the drug chlorphentermine (see chap. 2). Steatosis is particularly common in the liver as this organ has a major role in lipid metabolism (Fig. 6.15). The lipid may appear in the cell as many small droplets or as one large droplet. Interference with lipid metabolism can occur at several points ... 

Metabolism studies to assess the organ and cellular response to the presence of the ingredient. A relatively inert ingredient can be metabolized to a biologically potent compound that has extreme toxicity. 

It is necessary to appreciate both for a mechanistic view of toxicology. The first of these includes the absorption, distribution, metabolism, and excretion of xenobiotics, which are all factors of importance in the toxic process and which have a biochemical basis in many instances. The mode of action of toxic compounds in the interaction with cellular components, and at the molecular level with structural proteins and other macromolecules, enzymes, and receptors, and the types of toxic response produced are included in the second category of interaction. However, a biological system is a dynamic one, and therefore a series of events may follow the initial response. For instance, a toxic compound may cause liver or kidney damage and thereby limit its own metabolism or excretion. 

For many years, the cytoprotective effects of plant phenolic compounds were attributed to their ability to direct scavenge oxidants and free radicals. However, as discussed in the last section, this concept is oversimplified and misleading. More and more evidence suggess that plant phenolic compounds could interact with cellular components and trigger a series of cellular responses, which are able to modulate the redox status of the cells and protect the cells from potentially toxic electrophiles/oxidants. 

C. acuminata aqueous extract modified 12 proteins in tomato roots, decreasing the majority of them. The 23 amino acids of the N-terminal of protein 5 of tomato (37.5 kDa, 100% increase) showed 95% similarity to the glutathione S-transferases of other Solanaceae. In plants, GSTs play roles in normal cellular metabolism, as well as in the detoxification of a wide variety of toxic compounds. GSTs have been involved in numerous stress responses, including pathogen... 

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