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.