Acetaminophen hepatotoxicity is characterized by glutathione depletion, cellular necrosis, and, in some instances, by the induction of lipid peroxidation. Silybin dihemisuccinate, a soluble form of the flavonoid silymarin, protects rats against liver glutathione depletion and lipid peroxidation induced by acute acetaminophen intoxication. Other biochemical parameters such as serum transaminases did not show the drastic increase observed under acetaminophen intoxication when animals were treated with the flavonoid. Preliminary results suggest that silybin dihemisuccinate may be another antidote against acetaminophen hepatotoxicity.
Acetaminophen hepatotoxicity is characterized by glutathione depletion and the formation of the reactive electrophilic metabolite N-acetyl-p-benzoquinone imine. The induction of oxidative stress, expressed as lipid peroxidation, is controversial in acute acetaminophen intoxication. Isolated rat hepatocytes develop spontaneously or when incubated with buthionine sulfoximide, a progressive lipid peroxidation which may be inhibited by the antioxidant flavonoid silybin. When cells are incubated with acetaminophen, lipid peroxidation is not observed, this antilipoperoxidative effect being potentiated by silybin. It is proposed that when hepatocytes are incubated with a high concentration of acetaminophen, the drug may accumulate in the cells due to saturation and/or inhibition of detoxification pathways (as in the case of silybin). Under these conditions the development of hepatocyte oxidative stress may be inhibited due to the antioxidant behaviour of acetaminophen.
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