THE EFFECT OF ARTESUNATE ON BLEOMYCIN-INDUCED PULMONARY FIBROSIS

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.