Effect of riboflavin status on acetaminophen toxicity in the rat.

The effect of riboflavin status on acetaminophen hepatotoxicity was determined in the rat. Groups of rats were fed one of the following diets: "riboflavin-free" (RFF), low riboflavin (LRF), high riboflavin (HRF), or high riboflavin pair-fed (HRF pair-fed) with RFF group. After riboflavin deficiency was established by determining erythrocyte glutathione reductase activity coefficient, rats in all groups were administered a toxic dose of acetaminophen (1 g/kg body weight) orally. Their controls were given the vehicle alone. All animals were killed 24 h later and hepatotoxicity was assessed by the elevation of serum transaminases and by a necrotic score based on histological examination. The RFF diet induced biochemical riboflavin deficiency, decreased food intake and body weight gain, and was associated with almost complete protection against acetaminophen toxicity. Rats on the LRF diet, with less severe riboflavin deficiency and no significant change in weight gain, showed some necrosis, but it was much less than in the HRF ad libitum-fed rats. The HRF pair-fed rats with no biochemical riboflavin deficiency but with considerable growth retardation also showed very little hepatic necrosis. Our results suggest that riboflavin deficiency protects rats against acetaminophen toxicity but it is confounded by decreased food consumption and body weight.