The Long-Term Effect of L-Glutamine Administration in Sickle Cell Disease Related Liver Damage

Introduction: Sickle Cell Disease (SCD) is an autosomal recessive genetic disorder in the β-globin gene resulting from a point mutation at its sixth position where hydrophilic glutamic acid substitute with hydrophobic valine that results in mutated sickled hemoglobin. This mutation, which occurs in both copies of the gene, promotes hemolysis, vaso-occlusion, and sterile inflammation. SCD patients experiences serious health complications including multi organ failure including liver failure. Currently, there are no effective treatment available for SCD related liver problems.

Methods: In the present study, we have studied the long-term effect (for up to eight weeks) of L- glutamine administration (10-12 mg/mL) via drinking water on liver pathophysiology using quantitative liver intravital microscopy, advanced imaging, and biochemical analysis in humanized SCD mice.

Results: We found that oral L-glutamine administration significantly reduced the accumulation of iron, heme, and hemoglobin in liver of SCD mice but had no effect on ameliorating liver vaso-occlusion and liver fibrosis. We also found the reduced expression of Kupffer cells after L-glutamine administration which may led to the failure of the resolution of fibrosis and hepatic cell death. Moreover, the balance between proinflammatory vs anti-inflammatory macrophages were impaired in SCD mice liver post L-glutamine treatment. We also found activation of hepatic stellate cell markers including α-SMA, collagenase 1 and 2 post L-glutamine treatment in SCD mice liver.

Conclusion: Our current study highlights the long-term effects of L-glutamine in SCD mouse liver. Interestingly, despite a considerable decrease in hepatic heme-hemoglobin-iron accumulation, chronic liver injury did not ameliorate post-L-glutamine treatment suggesting the need to investigate the long-term effects of L-glutamine therapy on vaso-occlusion, Kupffer cell expression, hepatic cell death, and liver fibrosis in SCD patients.

No relevant conflicts of interest to declare.