Abstract
Despite new drug alternatives, no curative treatment for idiopathic pulmonary fibrosis (IPF) currently exists. This study aimed to evaluate the effects of artesunate on fibrosis, pulmonary hypertension, and inflammation-related changes in IPF. We divided a total of 32 male Wistar albino rats into four groups: a control group (group A, n=7), a group receiving artesunate (group B, n=7), a group receiving bleomycin (group C, n=9), and a group receiving both bleomycin and artesunate (group D, n=9). Groups A and B received intratracheal saline (0.1 mL), and groups C and D received intratracheal bleomycin (2.5 mg/kg). Groups A and C received intraperitoneal (i.p.) saline (0.1 mL/day), and groups B and D received i.p. artesunate (30 mg/kg/day) for 21 days. We measured the rats' exercise capacity by using a treadmill. We also examined heart and pulmonary tissues for right ventricular hypertrophy (RVH) and pulmonary arteriolar wall thickness for fibrosis, respectively. Finally, for immunohistochemistry, we performed Masson's trichrome stain and a macrophage marker antibody. The rats' measured exercise capacity was 1665 ± 145 m in the control group, 1142 ± 280 m in the group receiving bleomycin, 1490 ± 185 m in the group receiving artesunate, and 1207 ± 231 m in the group receiving both bleomycin and artesunate. The intergroup difference was statistically significant (p=0.001), but the difference between the bleomycin + artesunate and bleomycin-only groups was not statistically significant (p=0.95). RVH was common in the bleomycin group (0.44 ± 0.02). The difference between the bleomycin + a rtesunate and bleomycin groups was significant (0.37 ± 0.03). The medial wall of the pulmonary arterioles was thicker in bleomycin recipients than in artesunate recipients and controls, whereas it was thinner in bleomycin + artesunate recipients (p<0.001, p=0.026, respectively). Fibrosis and inflammatory changes improved in the bleomycin + artesunate group (p<0.001). The authors conclude that artesunate improved fibrosis, inflammatory changes, medial layer thickness of the pulmonary arterioles, and RVH in rats with bleomycin-induced pulmonary fibrosis.