Modulation of Ferroptosis Biomarkers by Thinned Apple Polyphenols Extract in Acute and Chronic Lung Injuries

ABSTRACT Acute and chronic lung injuries are characterized by a large amount of ROS, pro‐inflammatory leukocytes and ferroptosis, resulting in alveolar injury. Nowadays, there is great interest in the bioactive compounds obtained from the waste products deriving from agriculture and the food industry. Thinned young apples are particularly rich in polyphenols, more than 10‐fold with respect to harvested apples, and have antioxidant and anti‐inflammatory activities. Therefore, the aim of this study is to investigate whether modulation of ferroptosis biomarkers by thinned apple polyphenols (TAP) extract was able to reduce lung injuries in two experimental model: acute lung injury (ALI) and bleomycin‐induced idiopathic pulmonary fibrosis (IPF). Our results demonstrated that TAP extract was able to inhibit the ferroptosis, modulating the main biomarkers: malondialdehyde, NADPH oxidase‐4, glutathione peroxidase 4 and ferritin heavy chain 1. This modulation is probably due to Nrf2 activation, negative regulator of ferroptosis, by TAP extract and consequently activating the production of antioxidant enzymes. This induced histological alteration, cytokines release and fibrosis in the alveoli and lung parenchyma. Collectively, these results demonstrated that TAP extract was able to reduce ferroptosis in acute and chronic lung injury models, suggesting it as a potential biomarker for early diagnosis and intervention timely.