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Biochemical effects of dithiolthiones
Abstract:
Administration of dithiolthiones to mice in single intragastric doses (2-4 mmol/kg body weight) or in the diet (0.5% for 14 days), and to rats in the diet (0.1% for 14 days) was found to increase glutathione levels and the activities of a number of enzymes in various tissues including the liver and lung. The enzymes affected were glutathione transferases (with chlorodinitrobenzene or dichloronitrobenzene), quinone and glutathione reductase, and glucose-6-phosphate and 6-phosphogluconate dehydrogenase, all of which are involved directly or indirectly in the detoxication of xenobiotics, including carcinogens. The dithiolthiones tested in mice were oltipraz, ADT, 116L and 129L, and in rats, oltipraz. Intragastric administration of dithiolthiones (oltipraz, ADT or 116L; two doses each of 1 g/kg body weight) did not increase glutathione levels or enzyme activities in murine mammary adenocarcinoma transplants. Increases in glutathione levels and enzyme activities similar to those found with dithiolthiones were observed when a semi-synthetic diet containing 10-40% lyophilized cabbage was fed to mice for 30 days. Dithiolthiones that are present in cabbage may play a role in the protective actions of diets high in vegetables against the toxic actions of xenobiotics. The biochemical effects of dithiolthiones reported here may account for the protective actions of these compounds.
Insights
Dithiolthiones, found in cabbage, boost detoxifying enzymes and glutathione levels in mice and rats. These compounds may explain how vegetable-rich diets protect against harmful xenobiotics.
Area of Science:
- Biochemistry
- Toxicology
- Nutritional Science
Background:
- Dithiolthiones are compounds found in cruciferous vegetables.
- These compounds are known to influence metabolic pathways.
- Their role in xenobiotic detoxification and cancer prevention is of interest.
Purpose of the Study:
- To investigate the biochemical effects of dithiolthiones in vivo.
- To determine if dithiolthiones enhance detoxification enzymes and glutathione levels.
- To explore the potential role of dietary dithiolthiones in chemoprotection.
Main Methods:
- Administration of dithiolthiones (oltipraz, ADT, 116L, 129L) to mice and rats via single doses or dietary inclusion.
- Measurement of glutathione levels and activities of key detoxification enzymes (glutathione transferases, reductases, dehydrogenases).
- Assessment of effects on murine mammary adenocarcinoma transplants and on mice fed lyophilized cabbage.
Main Results:
- Dithiolthiones significantly increased glutathione levels and activities of detoxification enzymes in the liver and lungs of mice and rats.
- Enzymes affected include glutathione transferases, glutathione reductase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase.
- No significant increase in these markers was observed in murine mammary adenocarcinoma transplants.
- Feeding mice a diet with lyophilized cabbage also increased glutathione and enzyme activities, suggesting a role for dietary dithiolthiones.
Conclusions:
- Dithiolthiones enhance the body's natural detoxification systems by increasing glutathione and key enzyme activities.
- These biochemical effects provide a potential mechanism for the protective actions of dithiolthiones and vegetable-rich diets against xenobiotics.
- Dietary dithiolthiones, present in vegetables like cabbage, may contribute to cancer chemoprevention.
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