Drug Discov Ther. 2020;14(6):304-312. (DOI: 10.5582/ddt.2020.03112)

5-Aminolevulinic acid combined with sodium ferrous ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC-1α activation

Wang ZD, Ma K, Liu C, Hu X, Que WT, Ito H, Takahashi K, Nakajima M, Tanaka T, Ren K, Guo WZ, Yi SQ, Li XK


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-γ coactivator (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.

KEYWORDS: 5-aminolevulinic acid, acute graft-versus-host disease, liver injury, inflammatory cytokines, PGC-1α.

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