Neuroprotective Effect of Creatine and Pyruvate on Enzyme Activities of Phosphoryl Transfer Network and Oxidative Stress Alterations Caused by Leucine Administration in Wistar Rats

Abstract

Maple syrup urine disease is an autosomal metabolic disease caused by a deficiency of branched-chain α-keto acid dehydrogenase complex activity. In this disease occur the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and their corresponding branched-chain α-keto acids in the tissues and body fluids. The affected patients may present psychomotor development delay and mental retardation. The pathophysiology of maple syrup urine disease is not entirely understood, but leucine seems to be the primary neurotoxic metabolite. Creatine and pyruvate are energetics and antioxidants substances. In this study, we investigated the effects of leucine administration and co-administration of creatine plus pyruvate on several parameters of oxidative stress and phosphoryl transfer network in cerebral cortex and hippocampus of Wistar rats treated from the 8th to the 21st postpartum day. Leucine induced oxidative stress and diminished the activities of pyruvate kinase, adenylate kinase, cytosolic and mitochondrial creatine kinase. Co-administration of creatine plus pyruvate prevented the alterations provoked by leucine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that chronic administration of leucine may stimulate oxidative stress and alters the enzymes of phosphoryltransfer network in the cerebral cortex and hippocampus of the rats. It is possible that these effects may contribute, along with other mechanisms, to the neurological dysfunction found in patients affected by maple syrup urine disease. In this case, it is possible that creatine plus pyruvate supplementation could benefit to the patients.

Dietary Supplementation With Creatine Pyruvate Alters Rumen Microbiota Protein Function in Heat-Stressed Beef Cattle

“…Thus, we hypothesized that CrPyr may enhance the synchronization of energy and nitrogen supply and be beneficial for ruminal characteristics and microbial growth, and our previous study has shown that dietary supplementation with CrPyr improved rumen microbial protein synthesis. Creatine and pyruvate are not only essential substrates for energetics but also critical antioxidants (Navrátil et al, 2009;Nagaraja, 2016;Rieger et al, 2017). The results in our previous study showed that dietary supplementation with CrPyr improved stress resistance and increased the antioxidant status and rumen fermentation of heat-stressed beef cattle (Liu et al, 2020).…”

Effects of rumen-protected creatine pyruvate on blood biochemical parameters and rumen fluid characteristics in transported beef cattle

“…While dietary supplementation with RP-CrPyr tended to decrease the amount of serum MDA, the result indicates that RP-CrPyr could reduce oxidative stress to some extent. This may be because creatine and pyruvate are both energetic and antioxidant substances [ 21 ], and RP-CrPyr can be absorbed in the small intestine in the form of creatine and pyruvate in beef cattle.…”

Improved antioxidant activity and rumen fermentation in beef cattle under heat stress by dietary supplementation with creatine pyruvate

“…In the current study, the serum MDA concentration was decreased, the activity of SOD in the serum was elevated, and the activity of LDH in the serum was reduced in the CrPyr groups compared with the control group. These differences may be attributed to the creatine and pyruvate, which are energetics and antioxidant substances (Rieger et al., 2017).…”

“…Creatine has antioxidant properties protecting cells against superoxide anion and peroxynitrite. Pyruvate is an antioxidant, anti‐inflammatory, and neuroprotective agent, and it readily scavenges hydrogen peroxide in cultured cells and prevents energy declines (Rieger et al., 2017). Therefore, it is speculated that the combination of creatine and pyruvate could prevent oxidative damage in ruminants suffering from heat stress.…”