5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC1-α activation.

Abstract

Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported. In this study, a murine aGvHD model was developed by transferring spleen cells from donor B6/N (H-2kb) mice into recipient B6D2F1 (H-2kb/d) mice. In addition to evaluating manifestations in aGvHD mice, we analyzed the serum ALT/AST levels, liver pathological changes, infiltrating cells and mRNA expression of inflammation-related cytokines and chemokines. 5-ALA/SFC treatment significantly ameliorated liver injury due to aGvHD and decreased the population of liver-infiltrating T cells, resulting in a reduced expression of pro-inflammatory cytokines and chemokines. Furthermore, the mRNA expression proliferator-activated receptor-γcoactivator (PGC-1α) was enhanced, which might explain why 5-ALA/SFC treatment downregulates inflammatory signaling pathways. Our results indicated that 5-ALA/SFC can ameliorate liver injury induced by aGvHD through the activation of PGC-1α and modulation of the liver mRNA expression of inflammatory-related cytokines and chemokines. This may be a novel strategy for treating this disease.

• Authors: Zhidan Wang, Kuai Ma, Chi Liu, Xin Hu, Weitao Que, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima, Tohru Tanaka, Ke Ren, Wen-Zhi Guo, Shuang-Qin Yi, Xiao-Kang Li
• Journal: Drug discoveries & therapeutics (Drug Discov Ther) Vol. 14 Issue 6 Pg. 304-312 (Jan 23 2021) ISSN: 1881-784X [Electronic] Japan
• PMID: 33390570 (Publication Type: Journal Article)

Chemical References

• 5-amino levulinic acid
• Cytokines
• Ferrous Compounds
• Levulinic Acids
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Sodium Citrate
• Citric Acid
• ferrous citrate
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Citric Acid
• Cytokines (genetics)
• Disease Models, Animal
• Drug Therapy, Combination
• Ferrous Compounds (administration & dosage, chemistry, pharmacology)
• Gene Expression Regulation (drug effects)
• Graft vs Host Disease (drug therapy, etiology, genetics)
• Levulinic Acids (administration & dosage, pharmacology)
• Liver (drug effects, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (genetics)
• Sodium Citrate (chemistry)
• T-Lymphocytes (metabolism)
• Treatment Outcome
• Up-Regulation