Route, dose and duration of exposure to cadmium-relevance to oxidative stress induction
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Cadmium (Cd) is a toxic metal currently ranked as seventh (out of 275) on ATSDR priority list of hazardous substances and it is considered as one of the most important occupational and environmental pollutants. This carcinogenic metal causes adverse effects in various tissues, particularly kidneys after prolonged exposure. However, the mechanisms of these toxic effects are still not completely understood. Literature data indicate different mechanisms of cadmium toxicity, oxidative stress being one of the most important. Experiments confirm that Cd, metal with no redox potential, can indirectly induce the production of reactive oxygen species (ROS) by affecting antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase), nonenzymatic antioxidants (glutathione, totalsulfhydryl groups, antioxidative vitamines), and Fenton metals, iron and copper. This chapter summarizes our investigations on cadmium-induced oxidative stres...s conducted on three different animal species: rabbits, mice and rats. Application of a single oral dose of 50 mg Cd/kg b.w. in rabbits showed increased levels of lipid peroxidation in blood 4-6 hours after Cd intoxication indicating early development of oxidative stress in conditions of acute Cd poisoning. Experiments carried out on mice showed that single oral exposure to 20 mg Cd/kg b.w. resulted in intensive ROS production in liver while subacute oral dose of 10 mg Cd/kg b.w. induced more pronounced effect in kidneys, thus indicating different effect of Cd intoxication depending on duration of Cd exposure. Further experiments performed on rats provided strong evidence that Cd can induce oxidative stress in both blood and liver after oral (30 mg Cd/kg b.w.) and intraperitoneal (1.5 mg Cd/kg b.w.) acute intoxication, althoughintraperitoneal administration showed more pronounced negative effects. Results of these studies demonstrate that oxidative stress is an important mechanism of Cd toxicity and that Cd ability to induce oxidative stress in different tissues depends on the route, dose and duration of exposure to this toxic metal.
Извор:Peroxidases: Biochemical Characteristics, Functions and Potential Applications, 2013, 159-175
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