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Bioactivation and Tissue Toxicity Lec 11
Bioactivation and Tissue Toxicity Lec 11
Free radicals are species containing an odd number of electron. They may
be positively charged (cation radical), negatively charged (anion radical) or
neutral radical.
R+ R- R
Cation radical Anion radical neutral radical
•An important class of free radicals is inorganic free radicals such as hydrogen
peroxide and superoxide anion.
•These oxidative moieties can cause tremendous tissue damage leading to
mutations or cancer.
•The potential toxicity of free radicals is far greater than that of the
electrophiles.
•Cellular defence mechanisms against free radicals include control imposed by
membrane structure, neutralization by glutathione, control exerted by non-
enzymatic antioxidant scavengers such as vitamin A, E and C and enzymatic
inactivation of oxygen derived free radicals.
• Generation of reactive metabolites is indicated by modification in enzyme activities,
formation of glutathione conjugates and depletion in tissue levels of glutathione.
Since the availability of glutathione in the body determines the threshold for toxic
response, thiols(e.g., N-acetyl cysteine) can be used to treat poisoning by drugs
such as paracetamol that yield reactive metabolites.