Safety analysis of eperisone administration
In clinical practice, existing IPF treatments, such as pirfenidone and
nintedanib, have been reported to induce adverse effects such as
increasing markers of liver damage in the plasma and gastrointestinal
disorders (Noble et al., 2011; Richeldi et al., 2014). Therefore, we
conducted a comprehensive analysis of markers for pancreatic, hepatic,
and renal damage in plasma. The dose of eperisone was five times higher
than the dose that showed efficacy for BLM-dependent pulmonary fibrosis.
As shown in Table 1, administration of BLM or BLM plus eperisone (250
mg/kg) did not significantly alter 12 plasma markers for pancreatic,
hepatic, and renal damage. In addition, no mouse exhibited diarrhea or
hemorrhagic stool in either group (Table 2). Furthermore, we also
examined gastric and colonic mucosal injury using hematoxylin and eosin
staining. As shown in Figure 5 and Table 2, the condition of the gastric
and colonic mucosa in mice treated with BLM or BLM plus eperisone (250
mg/kg) was unchanged compared with that in vehicle-treated mice, and no
gastric and colonic mucosal injury was observed. These results suggest
that eperisone may be able to suppress pulmonary fibrosis without
inducing adverse effects.