The role of oxidant/antioxidant system on bleomycin induced lung fibrosis and the effect of erdostein on fibrosis in rats

In this experimental study, bleomycine (BLM)-induced lung fibrosis was developed by single intratracheal injection of BLM. The levels of lipid peroxidation end products and antioxidative enzyme activities were studied. The effects of vitamin E (vit E) and erdostein on the parameters studied and lung fibrosis were also examined. For these purposes, rats were divided into four unequal groups: sham operation group (control, n=8), BLM group (n=9), vit E + BLM group (n=9) and erdostein + BLM group (n=10). Rats were received BLM by intratracheally in the BLM-applied groups, vit E by intraperitoneal injection in vit E + BLM group, erdosteine by orally in erdosteine + BLM group. Hidroxyproline (OH-P) levels were taken as the indicator of lung fibrosis as stated by previous studies. OH-P levels were found to be elevated in BLM group suggesting clearly the fibrosis in lung tissue (pO.0001). Tissue OH-P levels were decreased in vit E group compared to BLM group (p<0.0001), but it was still high compared to control group (p<0.0001). On the other hand, tissue OH-P levels were decreased in erdosteine group compared to both BLM group (p<0.0001) and contol group, but the last one was not statistically significant. According to the findings about OH-P, vit E and erdosteine are both effective inhibitor agents in coping with BLM-induced lung fibrosis. Erdosteine is more effective than vit E. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were found to be decreased (pO.0001); malondialdehyde (MDA) levels as an index of endogenous lipid peroxidation increased (pO.0001); myeloperoxidase (MPO) activities as an index of neutrophil invasion to the lung tissue increased (pO.0001) in BLM group compared to control group. SOD activities in vit E group were unchanged compared to both BLM and erdosteine groups and decreased compared to control group (p<0.001). GSH-Px activity in vit E group were increased compared to BLM group (p<0.019) and decreased compared to control group. Tissue MDA levels in vit E group were decreased compared with BLM group (pO.0001) and increased in control group (p<0.002). MPO activities were unchanged compared to BLM and increased compared to control group (pO.0001). In erdosteine group; SOD activities were found to be unchanged compared to BLM and vit E groups, decreased compared to control group (p<0.003); GSH-Px 60activities were found to be increased compared to BLM (pO.OOOl) and vit E (p<0.009) groups, decreased compared to control group (pO.OOOl); tissue MDA levels and MPO activities were found to be decreased compared to both BLM (pO.OOOl) and vit E (pO.OOOl) groups, statistically unchanged compared to control group. In conclusion, erdosteine may attenuate the BLM-induced lung fibrosis via its antioxidant properties and the inhibitory effects on the neutrophil sequestration into lung tissue, so scavenge the free oxygen radicals and it is more effective agent in comparison with vit E. In the light of these results, we may suggest that erdosteine may be used for two purposes; 1) to attenuate the fibrotic process in the patients with fibrotic lung diseases, 2) as a prophylactic agent in the human neoplasms in which BLM is the main anticancer drug used.