International immunopharmacology · 2025
5-aminolaevulinic acid with sodium ferrous citrate alleviated kidney injury and fibrosis in a unilateral ureteral obstruction model.
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Ma Kuai, Fujino Masayuki, Yang Yang, Ding Zhaolun, Hu Xin, Ito Hidenori, Takahashi Kiwamu, Nakajima Motowo, Isaka Yoshitaka, Li Xiao-Kang
Аннотация
PURPOSE: This study aimed to investigate the potential therapeutic effects of 5-aminolaevulinic acid (5-ALA) combined with sodium ferrous citrate (SFC) on kidney injury and fibrosis in a mouse model of unilateral ureteral obstruction (UUO)-induced chronic kidney disease (CKD).
METHODS: A murine UUO model was used to mimic human CKD. The mice received daily intragastric administration of 5-ALA/SFC for 7 and 14 consecutive days. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels and histological evaluations were performed to assess the renal function parameters underlying 5-ALA/SFC treatment in the UUO model. Differentially expressed genes (DEGs) were analyzed by RNA sequencing (RNA-Seq), and the results were validated by quantitative real-time PCR (qRT-PCR). The severity of renal fibrosis was evaluated using Sirius red and Masson's trichrome (MT) staining techniques, while the expression of fibrosis-related genes was examined using western blotting and immunohistochemistry.
RESULTS: Our findings demonstrated that 5-ALA/SFC treatment improved UUO-induced renal dysfunction, attenuated tubular damage, and significantly reduced serum Cr and BUN levels as well as the mRNA expression and secretion of pro-inflammatory and programmed cell death-related cytokines in kidney tissues. Furthermore, 5-ALA/SFC suppressed renal tissue fibrosis and downregulated the mRNA and protein expression of fibrosis-related genes. Notably, treatment with 5-ALA/SFC led to the significant upregulation of protein expression levels of PPAR gamma-coactivator-1α (PGC-1α), indicating its role in inhibiting inflammation and fibrosis through the activation of the PGC-1α signaling pathway.
CONCLUSION: 5-ALA/SFC exhibits renoprotective effects in UUO-induced CKD by attenuating inflammation, cell death, and suppressing renal fibrosis. These findings suggest a specific renal protective mechanism for 5-ALA/SFC, highlighting its potential as a novel therapeutic agent for human CKD treatment.
METHODS: A murine UUO model was used to mimic human CKD. The mice received daily intragastric administration of 5-ALA/SFC for 7 and 14 consecutive days. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels and histological evaluations were performed to assess the renal function parameters underlying 5-ALA/SFC treatment in the UUO model. Differentially expressed genes (DEGs) were analyzed by RNA sequencing (RNA-Seq), and the results were validated by quantitative real-time PCR (qRT-PCR). The severity of renal fibrosis was evaluated using Sirius red and Masson's trichrome (MT) staining techniques, while the expression of fibrosis-related genes was examined using western blotting and immunohistochemistry.
RESULTS: Our findings demonstrated that 5-ALA/SFC treatment improved UUO-induced renal dysfunction, attenuated tubular damage, and significantly reduced serum Cr and BUN levels as well as the mRNA expression and secretion of pro-inflammatory and programmed cell death-related cytokines in kidney tissues. Furthermore, 5-ALA/SFC suppressed renal tissue fibrosis and downregulated the mRNA and protein expression of fibrosis-related genes. Notably, treatment with 5-ALA/SFC led to the significant upregulation of protein expression levels of PPAR gamma-coactivator-1α (PGC-1α), indicating its role in inhibiting inflammation and fibrosis through the activation of the PGC-1α signaling pathway.
CONCLUSION: 5-ALA/SFC exhibits renoprotective effects in UUO-induced CKD by attenuating inflammation, cell death, and suppressing renal fibrosis. These findings suggest a specific renal protective mechanism for 5-ALA/SFC, highlighting its potential as a novel therapeutic agent for human CKD treatment.