Creatine and pyruvate prevent behavioral and oxidative stress alterations caused by hypertryptophanemia in rats

Abstract

It is known that the accumulation of tryptophan and its metabolites is related to brain damage associated with both hypertryptophanemia and neurodegenerative diseases. In this study, we investigated the effect of tryptophan administration on various parameters of behavior in the open-field task and oxidative stress, and the effects of creatine and pyruvate, on the effect of tryptophan. Forty, 60-day-old male Wistar rats, were randomly divided into four groups: saline, tryptophan, pyruvate + creatine, tryptophan + pyruvate + creatine. Animals received three subcutaneous injections of tryptophan (2 μmol/g body weight each one at 3 h of intervals) and/or pyruvate (200 μg/g body weight 1 h before tryptophan), and/or creatine (400 μg/g body weight twice a day for 5 days before tryptophan twice a day for 5 days before training); controls received saline solution (NaCl 0.85%) at the same volumes (30 μl/g body weight) than the other substances. Results showed that tryptophan increased the activity of the animals, suggesting a reduction in the ability of habituation to the environment. Tryptophan induced increase of TBA-RS and total sulfhydryls. The effects of tryptophan in the open field, and in oxidative stress were fully prevented by the combination of creatine plus pyruvate. In case these findings also occur in humans affected by hypertryptophanemia or other neurodegenerative disease in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanisms leading to the brain injury, suggesting that creatine and pyruvate supplementation could benefit patients affected by these disorders.

Automated Behavioral Phenotyping Reveals Presymptomatic Alterations in a SCA3 Genetrap Mouse Model

“…In the atxn3 gt/gt mutant mice, we also found an involvement of the tryptophan pathway, observing an increased expression of tryptophan in the striatum of mice. Hypertryptophanemia is linked to oxidative stress in rats (Andrade et al, 2012); both can be involved in brain dysfunction of various common neurodegenerative disorders (Reznick et al, 1993;Karelson et al, 2001;Mendez-Alvarez et al, 2001). In summary, we demonstrate that the automated homecage based system LabMaster detects behavioral alterations, which were previously unreported in presymptomatic atxn3 gt/gt mutant mice.…”

“…10A). The accumulation of tryptophan and its metabolites is related to brain damage associated with neurodegenerative diseases (Andrade et al, 2012). Analysis of tryptophan and xanthurenic acid in the striatum of atxn3 gt/gt mutant mice in comparison to wild type littermates showed a significant increase of tryptophan levels at the age of 3 months (P ¼ 0.003) and in phenotypic mutant mice (P ¼ 0.018).…”

Tryptophan-Derived 3-Hydroxyanthranilic Acid Contributes to Angiotensin II–Induced Abdominal Aortic Aneurysm Formation in Mice In Vivo

“…Hypertryptophanemia 33–35 is a rare autosomal recessive metabolic disorder that results in a massive buildup of Trp in the blood. 36, 37 The addition of 500 µMTrp to HASMCs did not affect MMP2 expression (Supplementary Fig.…”

Antioxidant Effect of Chrysanthemum morifolium (Chuju) Extract on H2O2-Treated L-O2 Cells as Revealed by LC/MS-Based Metabolic Profiling

“…Moreover, antioxidants contribute to decreased levels of creatine kinase activity in serum; creatine and its metabolite creatine phosphate can also act as antioxidants and prevent behavioral and oxidative stress alterations. Their metabolism is disrupted by redox disorders [ 15 , 16 ]. It follows that the profile of metabolites can accurately reflect the body’s redox levels and help reveal the involved molecular mechanisms.…”