1.Comparison of therapeutic efficacy of ferroptosis inhibitor liproxstatin-1 and antioxidant N-acetylcysteine in bleomycin-induced pulmonary fibrosis
Fang CHEN ; Liang YUAN ; Ge WANG ; Shiting GHEN ; Zeguang ZHENG
Chinese Journal of Pathophysiology 2025;41(1):28-35
AIM:To compare the therapeutic effects of liproxstatin-1(LIP-1)and N-acetylcysteine(NAC)in bleomycin(BLM)-induced pulmonary fibrosis.METHODS:The mice were randomly divided into the control,model(BLM),BLM+NAC,BLM+LIP-1,NAC and LIP-1 groups.The BLM+NAC and BLM+LIP-1 groups were treated with NAC by intratracheal drip and LIP-1 by intraperitoneal injection,respectively,1 day before BLM tracheal instillation.The other groups received intraperitoneal injection of the same volume of co-solvent and intragastric instillation of saline.Fourteen days after a BLM challenge,the degree of lung fibrosis and the expression levels of alveolar epithelial cell mark-ers and ferroptosis-related molecules were assessed in each group.RESULTS:LIP-1 treatment more significantly im-proved the BLM-induced decrease in body weight(P＜0.01)and survival rate in mice compared with NAC.LIP-1 more significantly reduced the severity of pulmonary fibrosis and improved collagen deposition compared with NAC.LIP-1 also more significantly alleviated alveolar structural disruption,and more significantly inhibited the decrease in the alveolar epi-thelial cell markers podoplanin and surfactant protein C,as well as epithelial-mesenchymal transition,compared with NAC.LIP-1 was a more potent inhibitor of the BLM-induced increase in ferroptosis and its related molecule Heme oxygen-ase-1 than NAC.CONCLUSION:LIP-1 treatment is more effective than NAC in alleviating pulmonary fibrosis.Mecha-nistically,this finding may be related to the ability of LIP-1 to inhibit ferroptosis in alveolar epithelial cells.This study pro-vides new insights into the treatment of pulmonary fibrosis and lays the foundation for the clinical application of LIP-1.
2.Comparison of therapeutic efficacy of ferroptosis inhibitor liproxstatin-1 and antioxidant N-acetylcysteine in bleomycin-induced pulmonary fibrosis
Fang CHEN ; Liang YUAN ; Ge WANG ; Shiting GHEN ; Zeguang ZHENG
Chinese Journal of Pathophysiology 2025;41(1):28-35
AIM:To compare the therapeutic effects of liproxstatin-1(LIP-1)and N-acetylcysteine(NAC)in bleomycin(BLM)-induced pulmonary fibrosis.METHODS:The mice were randomly divided into the control,model(BLM),BLM+NAC,BLM+LIP-1,NAC and LIP-1 groups.The BLM+NAC and BLM+LIP-1 groups were treated with NAC by intratracheal drip and LIP-1 by intraperitoneal injection,respectively,1 day before BLM tracheal instillation.The other groups received intraperitoneal injection of the same volume of co-solvent and intragastric instillation of saline.Fourteen days after a BLM challenge,the degree of lung fibrosis and the expression levels of alveolar epithelial cell mark-ers and ferroptosis-related molecules were assessed in each group.RESULTS:LIP-1 treatment more significantly im-proved the BLM-induced decrease in body weight(P＜0.01)and survival rate in mice compared with NAC.LIP-1 more significantly reduced the severity of pulmonary fibrosis and improved collagen deposition compared with NAC.LIP-1 also more significantly alleviated alveolar structural disruption,and more significantly inhibited the decrease in the alveolar epi-thelial cell markers podoplanin and surfactant protein C,as well as epithelial-mesenchymal transition,compared with NAC.LIP-1 was a more potent inhibitor of the BLM-induced increase in ferroptosis and its related molecule Heme oxygen-ase-1 than NAC.CONCLUSION:LIP-1 treatment is more effective than NAC in alleviating pulmonary fibrosis.Mecha-nistically,this finding may be related to the ability of LIP-1 to inhibit ferroptosis in alveolar epithelial cells.This study pro-vides new insights into the treatment of pulmonary fibrosis and lays the foundation for the clinical application of LIP-1.
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