Biochemical studies on the mechanism of difference in the renal toxicity of 5-hydroxy-L-tryptophan between Sprague Dawley and Wistar rats.
The biochemical mechanisms of the renal toxicity of 5-hydroxy-L-tryptophan to rats were studied using Wistar and Sprague Dawley rats, which had different LD50 values. When the amino acid was injected intraperitoneally, Wistar rats, which had a low LD50 value of 5-hydroxy-L-tryptophan, excreted larger amonts of serotonin and smaller amounts of 5-hydroxyindole acetic acid into the urine than Spraque Dawley rats, which had a high LD50 value. The activity of renal aromatic L-amino acid decarboxylase was higher in Wistar rats than in Sprague Dawley rats, while the activity of renal aromatic amino acid transaminase was in an opposite relationship. The activity of renal monoamine oxidase was almost the same in both strains and the activity of renal UDP glucuronyltransferase in Wistar rats was higher than in Sprague Dawley rats. Since the renal damage caused in rats by 5-hydroxy-L-tryptophan was very similar to that caused by serotonin, the amine formed from the administered amino acid was thought to be an important factor for the renal necroses, and difference in serotonin formation from the administered precursor amino acid may be one of the important factors leading to the difference in LD50 values in the two strains of rats.
D006916:5-Hydroxytryptophan / Q000633:toxicity* / Q000652:urine; D000596:Amino Acids; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D000637:Transaminases / Q000378:metabolism
D000596:Amino Acids; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D008995:Monoamine Oxidase; D014453:Glucuronosyltransferase; D000637:Transaminases; D002262:Carboxy-Lyases