Evaluation of oxidative damage to biomolecules and inflammation in patients with urea cycle disorders

Lopes, Franciele Fátima; Faverzani, Jéssica Lamberty; Hammerschmidt, Tatiane Grazieli; Delgado, Camila Aguilar; Oliveira, Julia Ferreira de; Wajner, Moaçir; Vargas, Carmen Regla

doi:10.1016/j.abb.2023.109526

Cited by 3 publications

(4 citation statements)

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“…The levels of Orn and Orn/Cit ratio were up-regulated in AHU and gout compared with control group, and Arg levels were only increased in gout compared with AHU. Orn, Arg, and Cit take part in the urea metabolism, and urea cycle disorders could influence oxidative stress [ 41 ]. A previous study showed distinct serum metabolomic signatures between AHU and gout, and arginine metabolism seems to play a crucial role [ 18 ], which were consistent with our finding from pathway analysis.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology

Liu,

et al. 2023

J Orthop Surg Res

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Background Gout is the most common inflammatory arthritis and closely related to metabolic syndrome, leading to excruciating pain and the decline in quality of patients’ life. However, the pathogenesis of gout is still unclear, and novel biomarkers are demanded for the early prediction and diagnosis of gout. Objective This study aimed at profiling the dysregulated metabolic pathways in asymptomatic hyperuricemia (AHU) and gout and elucidating the associations between AHU, gout and metabolomics, which may aid in performing gout screening. Methods A total of 300 participants, including 114 healthy controls, 92 patients with AHU, and 94 patients with gout, were analyzed by using a combination of dried blood spot (DBS) sampling and mass spectrometry (MS) technology. Multiple algorithms were applied to characterize altered metabolic profiles in AHU and gout. The mainly altered metabolites were identified by random forest analysis. Results There were significant differences in AHU and gout compared with control group. The altered metabolites were involved in oxidation of fatty acids, carnitine synthesis, urea cycle, and amino acid metabolism in AHU and gout. Random forest classification of 16 metabolites yielded 3 important features to distinguish gout from AHU. Conclusions Distinct metabolomic signatures were observed in AHU and gout. The selected metabolites may have the potential to improve the early detection of gout.

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Section: Discussionmentioning

confidence: 99%

Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology

Liu,

et al. 2023

J Orthop Surg Res

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“…Hyperammonemia and hyperglutaminemia also impact neuronal energy production and utilization, autophagy, signaling pathways, and oxidative & nitrosative stress [7,9]. In the setting of NMDA-activation and intracranial hypertension, a positive feedback loop of neuronal irritability, poor perfusion, cellular signaling abnormalities, and stress results in astrocyte apoptosis, which results in poor energy delivery to neurons as well as decreased glutamate uptake.…”

Section: Hyperammonemic Injurymentioning

confidence: 99%

“…Deficiencies in the urea cycle all yield hyperammonemia, which results in broad oxidative injury and inflammation, with the most harmful effects seen in the brain [7]. In the brain, ammonia is converted to glutamine in astrocytes, by glutamine synthetase.…”

Section: Introductionmentioning

confidence: 99%

“…In the setting of NMDA-activation and intracranial hypertension, a positive feedback loop of neuronal irritability, poor perfusion, cellular signaling abnormalities, and stress results in astrocyte apoptosis, which results in poor energy delivery to neurons as well as decreased glutamate uptake. Other cell types are also injured and contribute to inflammatory activation and alterations in the blood brain barrier [7,9,10]. Rapid cellular injury results, resulting in seizures, cerebral edema with intracranial hypertension, coma and death [2 ▪ ,9] (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Urea cycle disorders in critically Ill adults

Long,

Kruser,

Quinonez

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Urea cycle disorders (UCDs) cause elevations in ammonia which, when severe, cause irreversible neurologic injury. Most patients with UCDs are diagnosed as neonates, though mild UCDs can present later - even into adulthood - during windows of high physiologic stress, like critical illness. It is crucial for clinicians to understand when to screen for UCDs and appreciate how to manage these disorders in order to prevent devastating neurologic injury or death. Recent findings Hyperammonemia, particularly if severe, causes time- and concentration-dependent neurologic injury. Mild UCDs presenting in adulthood are increasingly recognized, so broader screening in adults is recommended. For patients with UCDs, a comprehensive, multitiered approach to management is needed to prevent progression and irreversible injury. Earlier exogenous clearance is increasingly recognized as an important complement to other therapies. Summary UCDs alter the core pathway for ammonia metabolism. Screening for mild UCDs in adults with unexplained neurologic symptoms can direct care and prevent deterioration. Management of UCDs emphasizes decreasing ongoing ammonia production, avoiding catabolism, and supporting endogenous and exogenous ammonia clearance. Core neuroprotective and supportive critical care supplements this focused therapy.

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Metabolomics analysis of splenectomy of Nile tilapia (Oreochromis niloticus) reveals the spleen involved in regulating liver lipids and amino acids metabolism

Tao,

Du,

Jiang

et al. 2024

Front. Mar. Sci.

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The liver is essential for nutritional balance in fish, and liver damage in farmed fish often arises from factors like overfeeding, causing various health issues. Clinical observations indicate that liver diseases frequently involve spleen dysfunction, and there is evidence to suggest that the spleen has a significant impact on liver function. However, there has been no discussion on the role of the spleen in maintaining liver health in fish. To understand the role of fish spleen in liver metabolism, this study selected Nile tilapia (Oreochromis niloticus) as the experimental material and first established a tilapia splenectomy model. Various biochemical parameters of the liver and serum were measured, and the liver metabolism characteristics of the splenectomy group (SP group) and the sham operation group (SO group) were analyzed using metabolomics. After splenectomy, biochemical parameters of the liver and serum showed abnormalities, including significant increases in total cholesterol (T-CHO) and serum total bile acid (TBA) levels, alongside a significant decrease in liver TBA levels, suggesting impaired metabolic function and cholesterol deposition in the liver. Metabolomics analysis showed that metabolites such as lipids, lipid-like molecules, and organic acids and derivatives were differentially regulated between the SO and SP group. KEGG analysis showed that differential metabolites were enriched in lipid metabolism and amino acid metabolism. The metabolic pathway analysis of differential metabolites showed that after splenectomy, the low-activity urea cycle in the liver may accelerate lipid synthesis, while low concentrations of aromatic amino acids and taurine may inhibit lipid catabolism. These results indicate that after splenectomy, the liver metabolic capacity is impaired, which causes abnormal lipid metabolism by interfering with amino acid metabolism, making splenectomy tilapia liver at risk of liver disease, including cholesterol deposition, hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our results show that the spleen is involved in regulating liver lipid and amino acid metabolism, and the spleen may interfere with lipid metabolism by regulating liver amino acid metabolism. Our data can provide support for further research on liver and spleen functions and the immune-nutrient metabolism mechanisms in fish, as well as new ideas for healthy fish farming.

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Evaluation of oxidative damage to biomolecules and inflammation in patients with urea cycle disorders

Cited by 3 publications

References 64 publications

Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology

Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology

Urea cycle disorders in critically Ill adults

Metabolomics analysis of splenectomy of Nile tilapia (Oreochromis niloticus) reveals the spleen involved in regulating liver lipids and amino acids metabolism

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