Effects of Methionine and Inorganic Sulfate on Indole Toxicity and Indican Excretion in Rats

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Abstract
Indole toxicity and its prevention by dietary methionine supplements were studied in rats fed a low protein diet. Male weanling animals fed an 8% casein diet supplemented with 0.5% indole showed significant growth retardation as compared with controls fed an 8% casein diet alone. Larger indole supplements to the diet (1.0 and 2.0%) not only suppressed growth, but also produced hemolytic anemia and neurotoxicity, resulting in premature death, whereas smaller indole supplements were nontoxic. Addition of 0.125% methionine to 8% casein rat diets, supplemented with 0.5% indole, prevented growth retardation. Indican excretion varied with indole intake only with dietary concentrations below 0.5%. The effect of methionine administration on indican excretion, in animals on the 0.5% indole-supplemented diet, was dosage dependent, i.e., 0.125% of the amino acid did not significantly increase indican output, but above this level indican excretion increased with intake until a maximal indican output was achieved when the methionine supplement exceeded 0.5% of the diet. In further experiments, it was shown that in indole-fed rats, the level of indican excretion is a function of sulfur intake whether the sulfur is derived from sulfur-containing amino acids or inorganic sulfate. Inorganic sulfate cannot replace methionine to prevent growth retardation due to indole. It has been concluded that in rats there is a methionine requirement to prevent indole toxicity.