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Long-Term L-Glutamine Treatment Reduces Hemolysis Without Ameliorating Hepatic Vasoocclusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease
Katoch, O.; Ungalara, R.; Kaminski, T.; Li, Z.; Dubey, R.K.; Burholt, I.; Gudapati, S.; Pradhan-Sundd, T. Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease. Biomedicines2023, 11, 2412.
Katoch, O.; Ungalara, R.; Kaminski, T.; Li, Z.; Dubey, R.K.; Burholt, I.; Gudapati, S.; Pradhan-Sundd, T. Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease. Biomedicines 2023, 11, 2412.
Katoch, O.; Ungalara, R.; Kaminski, T.; Li, Z.; Dubey, R.K.; Burholt, I.; Gudapati, S.; Pradhan-Sundd, T. Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease. Biomedicines2023, 11, 2412.
Katoch, O.; Ungalara, R.; Kaminski, T.; Li, Z.; Dubey, R.K.; Burholt, I.; Gudapati, S.; Pradhan-Sundd, T. Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease. Biomedicines 2023, 11, 2412.
Abstract
Abstract: 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. Oral l-glutamine administration has been shown to reduce the frequency of pain crisis 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 SCD 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 level, but fails to ameliorate ischemic liver injury. Remarkably, we find that this failure in resolution of hepatobiliary injury and persistent liver fibrosis is associated with reduced expression of hepatic Kupffer cells post l-glutamine treatment. These findings establish the importance to investigate the long-term effects of l-glutamine therapy on liver pathophysiology in SCD patients.
Copyright:
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