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.