4. Metabolomic unveiled shared and unique metabolic pathway impacted by PFD or BIBF in silicosis development.
Coupled with prior transcriptomic evidence, it becomes imperative to comprehensively elucidate the mechanism underlying PFD and BIBF treatments for silicosis from a metabolic standpoint. Metabolomics-based insights indicate that the occurrence of fibrosis is associated with significant alterations in metabolites (Fig 5A) belonging to amino acid, nucleotide, lipid, and carbohydrate metabolic pathways (Fig 5B). Specifically, PFD has been identified to impact the metabolism of ether lipid, pentose phosphate pathway, steroid hormone et al. (Fig 5C, D), while BIBF influences the metabolism of neomycin, kanamycin and gentamicin, D-glutamine and D-glutamate and so on (Fig 5E, F). Through an integrated analysis, a holistic understanding of the intricate interplay between metabolism and the therapeutic interventions of PFD and BIBF in the context of treating silicosis can be obtained. Both two drugs primarily target 4 specific metabolic pathways involved in the development of silicosis, including purine metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and glutathione metabolism. However, there are differences in their metabolic mechanism of action. PFD specifically affects a pathway called pentose phosphate pathway that is associated with lung fibrosis (Aboushousha et al., 2021; Qiu et al., 2022), while BIBF primarily affects metabolic processes related to amino acids and carbohydrates (Fig 5G, H). Overall, PFD and BIBF aim to address the underlying metabolic dysregulation associated with the pathogenesis of silicosis. Furthermore, the unique impacts exhibited by these two drugs may suggest that their combined administration could potentially yield synergistic or additive effects, thereby maximizing therapeutic outcomes.