Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

Ceyhan, Güralp O.; Timm, Annette; Bergmann, Frank; Günther, A.; Aghdassi, Ali; Demir, Ihsan Ekin; Mayerle, Julia; Kern, Michael; Lerch, Markus M.; Büchler, Markus W.; Frieß, Helmut; Schemmer, Peter

doi:10.1159/000325972

Cited by 11 publications

(7 citation statements)

References 48 publications

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“…Glycine can be synthesized from hydroxyproline 20 and was inversely associated with the severity of CRS. An anti-inflammatory role for glycine has been previously reported in various proinflammatory diseases, including arthritis 23 and acute pancreatitis, 46 suggesting that these amino acids may form an anti-inflammatory biomarker axis in patients with r/r LBCL. Previous reports have shown a positive correlation between ICANS and post–CAR T-cell cerebrospinal fluid metabolites such as glutamate and quinolinic acid.…”

Section: Discussionmentioning

confidence: 93%

Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy

et al. 2023

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Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B cell lymphoma (r/r LBCL). However, widespread use is deterred by development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pre-treatment host metabolites that are associated with CRS and ICANS induced by Axicabtagene Ciloleucel or Tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed significant association between the abundance of specific pre-treatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q<.1) and ICANS (q<.25). Higher pre-treatment levels of plasma glucose, and lower levels of cholesterol and glutamate were associated with faster onset of CRS. On the other hand, low baseline levels of amino acids proline and glycine and secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pre-treatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients prior to anti-CD19 CAR T-cell therapy.

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Section: Discussionmentioning

confidence: 93%

Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy

et al. 2023

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“…The result is consistent with Cui et al (). The important finding that glycine may act as an anti‐inflammatory agent is based on the expression of GlyR on leukocytes including neutrophils, Kupffer cells and splenic and alveolar macrophages (El Hafidi et al, ; Ceyhan et al, ). Activation of GlyR on these cells can, as for neurons, result in hyperpolarization of the plasma membrane and thereby blunted increased intracellular calcium concentrations.…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolomics analysis reveals the effect of volatile oil from Angelica sinensis on LPS‐induced inflammation rats

Hua

Zhang

et al. 2018

Biomedical Chromatography

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Lipopolysaccharide (LPS)-induced inflammation occurs commonly and volatile oil fromAngelica sinensis (VOAS) can be used as an anti-inflammatory agent. The molecular mechanisms that allow the anti-inflammatory factors to be expressed are still unknown. In this paper, we applied gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-time-of-flight mass spectrometry (LC-Q/TOF-MS) based on a metabolomics platform coupled with a network approach to analyze urine samples in three groups of rats: one with LPS-induced inflammation (MI); one with intervention with VOAS; and normal controls (NC). Our study found definite metabolic footprints of inflammation and showed that all three groups of rats, MI, intervention with VOAS and NC have distinct metabolic profiles in urine. The concentrations of 48 metabolites differed significantly among the three groups. The metabolites in urine were screened by the GC-MS and LC-Q/TOF-MS methods.The significantly changed metabolites (p < 0.05, variable importance in projection > 1.5) between MI, NC and VOAS were included in the metabolic networks.Finally, hub metabolites were screened, including glycine, arachidonic acid, L-glutamate, pyruvate and succinate, which have high values of degree (k). the Results suggest that disorders of glycine, arachidonic acid, L-glutamate, pyruvate and succinate metabolism might play an important part in the predisposition and development of LPS-induced inflammation. By applying metabolomics with network methods, the mechanisms of diseases are clearly elucidated.

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“…83 Prior to induction of pancreatitis, rats were given intravenous doses of glycine. After treatment, it was noted that rats with mild cerulein-induced pancreatitis pretreated with glycine had less pancreatic necrosis and inflammation.…”

Section: Other Components and Functional Foodsmentioning

confidence: 99%

Nutritional advice for prevention of acute pancreatitis: review of current opinion

Lowe¹,

Sevilla²

2012

NDS

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Pancreatitis is inflammation of the pancreas that can be acute and self-limiting or, in a small percentage of patients, recurrent. Patients with recurrent episodes of acute pancreatitis (RAP) often progress to chronic pancreatitis. Pancreatitis in all forms causes significant economic and social burdens. Prevention of RAP may decrease those burdens and halt progression to chronic disease. Unfortunately, no therapy has proven effective at altering the course of RAP. While enteral nutritional therapy plays an important role in the treatment of acute pancreatitis during episodes, nutritional advice provided to patients in an attempt to prevent recurrent episodes has not proven effective in most cases. Discontinuing alcohol consumption and treating dyslipidemia with diet and medication can help patients with these issues. In patients whose pancreatitis is associated with celiac disease or eosinophilic gastroenteritis, a gluten-free diet and avoidance of food allergens can be effective in stopping RAP. Advice to take pancreatic enzyme replacement therapy, lose weight, control diabetes, decrease dietary sucrose, decrease dietary fat or avoid monosodium glutamate has little to no evidence of efficacy. Some studies suggest that an antioxidant cocktail may decrease the frequency of RAP and the intensity of chronic pain, but the evidence is weak. Nutritional therapy may have a role in the treatment of patients with RAP. At present, there are no clear guidelines for nutritional advice to give these patients. More studies are needed to identify nutritional interventions that will benefit patients with RAP.

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Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

Cited by 11 publications

References 48 publications

Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy

Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy

Urinary metabolomics analysis reveals the effect of volatile oil from Angelica sinensis on LPS‐induced inflammation rats

Nutritional advice for prevention of acute pancreatitis: review of current opinion

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