Protection from N-Nitrosodimethylamine Mediated Liver Damage by Indole-3-Carbinol, and Correlation with Nucleophilic Index Value

Indole-3-carbinol (I-3-C), a normal constituent of the human diet via cruciferous vegetables, was examined for its ability to protect mice against 24-hour N-nitrosodimethylamine (NDMA)-mediated hepatotoxicity. NDMA (20 mg/kg body weight) alone produced extensive hemorrhagic and centrolobular necrotic lesions, with a necrotic severity index of 3.0 ± 0.4 (scale of 0-5). Treatment with 50 mg/kg body weight of I-3-C by gavage, 1 hour prior to NDMA, substantially protected against hemorrhagic lesions. Furthermore, I-3-C lowered the NDMA-mediated tissue necrotic index to 1.5 ± 0.3, by reducing the extent of tissue necrosis rather than the severity in the necrotic region. Release of liver enzymes into the blood correlated with the histopathology; I-3-C reduced NDMA-mediated elevated activities of plasma alanine transaminase and ornithine transcarbamylase by 84% and 51.3%, repectively (Table 1). Plasma activities of these enzymes were used as indicators of hepatotoxicity. Although no changes in liver non-protein sulfhydryls were evident at 24 hours after NDMA, ascorbate levels were reduced to 40% of controls values. Treatment with I-3-C prior to NDMA prevented this decline in tissue ascorbate concentrations.