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Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion, and sterile inflammation. The administration of oral L-glutamine has been shown to reduce the frequency of pain...

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Autores principales: Katoch, Omika, Ungalara, Ramakrishna, Kaminski, Tomasz, Li, Ziming, Dubey, Rikesh K., Burholt, Isabella, Gudapati, Shweta, Pradhan-Sundd, Tirthadipa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526062/
https://www.ncbi.nlm.nih.gov/pubmed/37760853
http://dx.doi.org/10.3390/biomedicines11092412
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author Katoch, Omika
Ungalara, Ramakrishna
Kaminski, Tomasz
Li, Ziming
Dubey, Rikesh K.
Burholt, Isabella
Gudapati, Shweta
Pradhan-Sundd, Tirthadipa
author_facet Katoch, Omika
Ungalara, Ramakrishna
Kaminski, Tomasz
Li, Ziming
Dubey, Rikesh K.
Burholt, Isabella
Gudapati, Shweta
Pradhan-Sundd, Tirthadipa
author_sort Katoch, Omika
collection PubMed
description Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion, and sterile inflammation. The administration of oral L-glutamine has been shown to reduce the frequency of pain in SCD patients; however, the long-term effect of L-glutamine in SCD remains to be determined. To understand the long-term effect of L-glutamine administration in the liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic L-glutamine administration reduces hepatic hemoglobin–heme–iron levels but fails to ameliorate ischemic liver injury. Remarkably, we found that this failure in the resolution of hepatobiliary injury and persistent liver fibrosis is associated with the reduced expression of hepatic Kupffer cells post-L-glutamine treatment. These findings establish the importance of investigating the long-term effects of L-glutamine therapy on liver pathophysiology in SCD patients.
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spelling pubmed-105260622023-09-28 Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease Katoch, Omika Ungalara, Ramakrishna Kaminski, Tomasz Li, Ziming Dubey, Rikesh K. Burholt, Isabella Gudapati, Shweta Pradhan-Sundd, Tirthadipa Biomedicines Brief Report Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion, and sterile inflammation. The administration of oral L-glutamine has been shown to reduce the frequency of pain in SCD patients; however, the long-term effect of L-glutamine in SCD remains to be determined. To understand the long-term effect of L-glutamine administration in the liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic L-glutamine administration reduces hepatic hemoglobin–heme–iron levels but fails to ameliorate ischemic liver injury. Remarkably, we found that this failure in the resolution of hepatobiliary injury and persistent liver fibrosis is associated with the reduced expression of hepatic Kupffer cells post-L-glutamine treatment. These findings establish the importance of investigating the long-term effects of L-glutamine therapy on liver pathophysiology in SCD patients. MDPI 2023-08-29 /pmc/articles/PMC10526062/ /pubmed/37760853 http://dx.doi.org/10.3390/biomedicines11092412 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Katoch, Omika
Ungalara, Ramakrishna
Kaminski, Tomasz
Li, Ziming
Dubey, Rikesh K.
Burholt, Isabella
Gudapati, Shweta
Pradhan-Sundd, Tirthadipa
Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title_full Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title_fullStr Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title_full_unstemmed Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title_short Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
title_sort long-term l-glutamine treatment reduces hemolysis without ameliorating hepatic vaso-occlusion and liver fibrosis in a mouse model of sickle cell disease
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526062/
https://www.ncbi.nlm.nih.gov/pubmed/37760853
http://dx.doi.org/10.3390/biomedicines11092412
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