BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder
that has high mortality rates, and pharmacological therapies are so far
ineffective. The pathophysiology of ALI involves pulmonary oxidative
stress and inflammatory response. Fullerol is a carbon nanocomposite
that possesses antioxidant and anti-inflammatory properties. Here, we
evaluated the therapeutic potential of fullerol and its mechanisms in a
model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided
into ALI (paraquat alone), fullerol (paraquat plus fullerol), and
control groups. Survival curves were estimated using the Kaplan-Meier
method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin
staining were used to determine neutrophils infiltration, cytokines
production, and histopathological parameters in lung samples,
respectively. The antioxidant effect of fullerol was evaluated in
vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg)
markedly reduced the severe lung injury and high mortality rates
observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the
reactive oxygen species formation and lipid peroxidation seen in lungs
from ALI rats, and exhibited a potent concentration-dependent
(10 to 10 mg/ml) in vitro
antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited
neutrophils accumulation in bronchoalveolar lavage and lungs, and the
increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI
rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in
reducing pulmonary damage and ALI-induced mortality, highlighting its
therapeutic potential in an ALI condition. Searching for new
pharmacological therapies to treat ALI may be desirable especially in
view of the new coronavirus disease 2019 that currently plagues the
world.
Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT