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The biotransformation of a toxic compound usually, but not always, results in detoxification. It can, however, lead to the metabolic activation of foreign compounds. More than two decades ago, the term toxicodietetics was coined for the study of dietary factors in the alterations of toxicity — a term that was perhaps ahead of its time.
There are a multitude of dietary factors that can affect toxicity. Dietary factors can be associated with the exposure situation, ranging from factors such as palatability of the food to the physical volume or rate of food ingestion. Dietary factors can be responsible for producing changes in the body composition, physiological and biochemical functions, and nutritional status of subjects. These factors, and others, can have marked influences on the toxicity of substances.
It is customary to fast laboratory animals for toxicity studies, usually 2 h before killing them at the end of the study. Fasting the animals has been shown to increase catabolic effects and decrease liver glycogen stores. Laboratory animals are therefore fasted to decrease their liver glycogen, which interferes with the preparation of microsomal enzyme fractions. Also, fasting is done because the presence of food in the stomach impedes gastric absorption. Fasting is also a traditional procedure which was practiced by physicians on surgical patients to prevent regurgitation of fluids into the airways. However, evidence has shown that fasting affects mechanisms of drug metabolism, toxicokinetics, and toxicity. Fasting for as long as 8 h has been shown to reduce blood glucose and produce changes in the activity of several toxicant-metabolizing enzymes. In addition, fasting induces the activity of cytochrome P450 in the liver and kidneys of rats, and results in glutathione depletion and generation of reactive oxygen species (ROS), oxidative stress, lipid peroxidation and overall decreased detoxification.
Reduced caloric intakes increases the toxicity of caffeine and dichloro diphenyl trichlorotethane (DDT) in rats, and low-protein diets have been shown to increase the toxicity of several pesticides and other toxic agents. Contrarily, low-protein diets have been found to protect rats against the hepatotoxicity of carbon tetrachloride and dimethylnitrosamine exposure.
This is because the protective effects of low-protein diets are likely due to a decrease in microsomal enzyme systems, i.e., depressed protein availability for enzyme synthesis in protein-deficient animals. Diet can affect enzymatic mechanisms of detoxification in several ways. Dietary deficiencies of essential macro- or micronutrients that are required by metabolizing systems can lead to decreased activities of such enzyme systems.
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