lactoferrin and Pulmonary-Fibrosis

Severe acute respiratory syndrome 2019-new coronavirus (SARS-CoV-2) is a major global challenge caused by a pandemic disease, named 'COVID-19' with no effective and selective therapy available so far. COVID-19-associated mortality is directly related to the inability to suppress the viral infection and the uncontrolled inflammatory response. So, we investigated the antiviral efficiency of the nanofabricated and well-characterized lactoferrin-coated zinc nanoparticles (Lf-Zn-NPs) on SARS-CoV-2 replication and entry into host cells. Lf-Zn-NPs showed potent inhibition of the entry of SARS-CoV-2 into the host cells by inhibition of ACE2, the SARS-CoV-2 receptor. This inhibitory activity of Lf-Zn-NPs to target the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor offers potent protection against COVID-19 outbreaks. Moreover, the administration of Lf-Zn-NPs markedly improved lung fibrosis disorders, as supported by histopathological findings and monitored by the significant reduction in the values of CRP, LDH, ferritin, and D-dimer, with a remarkable rise in CD4+, lung SOD, GPx, GSH, and CAT levels. Lf-Zn-NPs revealed therapeutic efficiency against lung fibrosis owing to their anti-inflammatory, antioxidant, and ACE2-inhibiting activities. These findings suggest a promising nanomedicine agent against COVID-19 and its complications, with improved antiviral and immunomodulatory properties as well as a safer mode of action.

Topics: Angiotensin-Converting Enzyme 2; Antiviral Agents; COVID-19; Humans; Lactoferrin; Male; Metal Nanoparticles; Pulmonary Fibrosis; Rats; SARS-CoV-2; Zinc

This study investigated the ability of aerosolized bovine lactoferrin (bLF) to protect the lungs from injury induced by chronic hyperoxia. Female CD-1 mice were exposed to hyperoxia (FiO2 = 80 %) for 7 days to induce lung injury and fibrosis. The therapeutic effects of bLF, administered via an aerosol delivery system, on the chronic lung injury induced by this period of hyperoxia were measured by bronchoalveolar lavage, lung histology, cell apoptosis, and inflammatory cytokines in the lung tissues. After exposure to hyperoxia for 7 days, the survival of the mice was significantly decreased to 20 %. The protective effects of bLF against hyperoxia were further confirmed by significant reductions in lung edema, total cell numbers in bronchoalveolar lavage fluid, inflammatory cytokines (IL-1β and IL-6), pulmonary fibrosis, and apoptotic DNA fragmentation. The aerosolized bLF protected the mice from oxygen toxicity and increased the survival fraction to 66.7 % in the hyperoxic model. The results support the use of an aerosol therapy with bLF in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure or chronic obstructive pulmonary disease.

Topics: Administration, Inhalation; Animals; Apoptosis; Cattle; Cytokines; Disease Models, Animal; Drug Delivery Systems; Female; Humans; Hyperoxia; Immunologic Factors; Inflammation; Lactoferrin; Lung Injury; Mice; Mice, Inbred ICR; Pulmonary Fibrosis