Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Holeček, Milan; Vodeničarovová, Melita; Šiman, Pavel

doi:10.1111/iep.12231

Cited by 14 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 ). Unfortunately, it has been shown that phenylbutyrate activates the BCKD, resulting in decreases in BCAA and BCKA levels in blood plasma [ 55 , 56 ]. Marked decrease of BCAAs in UCD after phenylbutyrate treatment has been reported by Scaglia et al [ 57 ].…”

Section: Disorders With Decreased Bcaa Levelsmentioning

confidence: 99%

See 1 more Smart Citation

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

2018

Self Cite

View full text Add to dashboard Cite

Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness.In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles.The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes.It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.

show abstract

Section: Disorders With Decreased Bcaa Levelsmentioning

confidence: 99%

“…Current treatment of MSUD is based on protein restriction and synthetic formulas with reduced BCAA content. Perspective may be phenylbutyrate, which activates BCKD and decreases BCAA and BCKA levels [ 55 , 56 ]. Unfortunately, studies examining phenylbutyrate in MSUD patients are unique.…”

Section: Disorders With Enhanced Bcaa Levelsmentioning

confidence: 99%

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent random control trials using glycerol phenylbutyrate and sodium phenylbutyrate on patients who had two or more episodes of HE in the last 6 months indicated fewer recurrent episodes. Even though phenylbutyrate is well tolerated in adults with cirrhosis, it has been shown to decrease BCAA levels in blood plasma . This is probably due to enhanced glutamine depletion and removal from the body, which in turn activates BCAA catabolism.…”

Section: Treatment Of Hepatic Encephalopathymentioning

confidence: 99%

Mechanistic insight, diagnosis, and treatment of ammonia‐induced hepatic encephalopathy

Kenston

Song

Zhou

et al. 2018

J of Gastro and Hepatol

View full text Add to dashboard Cite

Hepatic encephalopathy is a neuropsychological syndrome due to biochemical disturbance of brain function in advanced liver disease patients. Diagnosis and treatment of the condition is very demanding and has negative toll on finances with increased healthcare utilization. The pathophysiology is not completely understood; however, there is evidence that ammonia plays an important role in the etiology. Conventional methods of solely relying on blood ammonia level to diagnose hepatic encephalopathy did not help much; likewise, the use of lactulose alone in treating hepatic encephalopathy has also been discouraged. This paper analyzed the current knowledge regarding the mechanism of how ammonia disrupts the normal brain function as well as the use of latest diagnosing tools including those under development to evaluate the neuropsychiatric state of patients and their quality of life. The efficacies of lactulose and rifaximin combination for short-term and long-term treatment in addition to nutritional interventions and other drugs undergoing clinical trials were also reviewed.

show abstract

“…The more pronounced atrophy of white muscles is observed in muscle wasting disorders, and the responses of red muscles to STZ and/or MSC therapy may differ. 37 The infusion of MSCs in diabetic animals promoted a significant improvement in motor function and increased the number of muscle fibres in spite of the absence of significant changes in CSA. However, the observed strong positive correlation between CSA and motor activity is noteworthy.…”

Section: Discussionmentioning

confidence: 99%

“…The reduction of myofibres and muscle mass was associated with both increased protein degradation and decreased protein synthesis in skeletal muscles causing the muscle weakness in T1D. The more pronounced atrophy of white muscles is observed in muscle wasting disorders, and the responses of red muscles to STZ and/or MSC therapy may differ . The infusion of MSCs in diabetic animals promoted a significant improvement in motor function and increased the number of muscle fibres in spite of the absence of significant changes in CSA.…”

Section: Discussionmentioning

confidence: 99%

Effects of mesenchymal stromal cells on motor function and collagen in the skeletal muscles of rats with type I diabetes

Luna

Russo

Sabadine

et al. 2019

Int J Experimental Path

View full text Add to dashboard Cite

Summary The present study aimed to evaluate the effects of mesenchymal stromal cell (MSC) transplantation on motor function and collagen organization in the muscles of rats with type 1 diabetes mellitus. Male Wistar rats were randomly assigned to three groups: control (C), diabetic (DM) and diabetic treated with MSCs (DM‐MSCs). Diabetes was induced by streptozotocin (50 µg/kg). Bone marrow cells were isolated from the tibia and femur. After 10 weeks of DM induction, the DM‐MSC rats received four i.p. injections of MSCs (1 × 106). Ten weeks after MSC transplantation, motor performance was evaluated by the rotarod test and the anterior tibial (TA) muscles were collected for morphometric and quantification of collagen birefringence by polarizing microscopy analysis. Motor performance of the DM group was significantly reduced when compared to the C group and increased significantly in the DM + MSC group. The TA muscle mass was significantly reduced in the DM and DM + MSC groups compared to the C group. The connective tissue increased in the DM group compared to the C group and decreased in the DM + MSC group. The percentage collagen birefringence decreased significantly in the DM group when compared to the C group and increased in the DM + MSC group. Motor performance was positively correlated with collagen birefringence and negatively correlated with percentage of connective tissue. The results indicate that MSC transplantation improves both motor function and the collagen macromolecular organization in type 1 DM.

show abstract

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Cited by 14 publications

References 29 publications

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

Mechanistic insight, diagnosis, and treatment of ammonia‐induced hepatic encephalopathy

Effects of mesenchymal stromal cells on motor function and collagen in the skeletal muscles of rats with type I diabetes

Contact Info

Product

Resources

About