This document summarizes a study investigating the potential protective role of ivermectin in acute lung injury (ALI) using lipopolysaccharide (LPS)- or bleomycin (BLM)-induced mouse models. The study found that ivermectin administration at doses of 1-2 mg/kg preserved alveolar structure and reduced inflammation, hemorrhage, and edema in the lungs of LPS- or BLM-treated mice. Ivermectin also inhibited neutrophil infiltration, myeloperoxidase activity, and phosphorylation of JNK and p38 MAPK proteins involved in inflammation. The results suggest ivermectin has strong anti-inflammatory effects and may help mitigate ALI by

1. Molecular biology seminar
III semester
UPB School of Medicine.
María Ángel Martínez Gutiérrez

2. Introduction.
Acute lung injury.
It is a relatively rare, potentially life-threatening
clinical syndrome characterized by acute
respiratory failure and noncardiogenic
pulmonary edema.
Various pathogenic factors in the pathogenesis
of ALI cause the injury of alveolar epithelial cells,
increased alveolar-capillary permeability,
extravasation of protein-rich fluid, and diffuse
interstitial edema.

3. Introduction.
Ivermectin is a commonly used broad-spectrum
antiparasitic drug, with clinical studies confirming
its safety and tolerability. Ivermectin also exhibits
antiviral effects against HIV-1, Dengue virus 1–4,
and SARS-CoV-2. More importantly, there is
evidence that ivermectin may help to control
inflammatory diseases.

4. Goal
"Here we investigated the potential
role of ivermectin in the pathogenesis
of acute lung injury (ALI) using the lipo-
polysaccharide (LPS)- or bleomycin
(BLM)-induced mice models."

5. 1 Collection of plasma and BALF 2 Immunohistochemistry of lung
Methods
Mice were euthanized with CO2 and
plasma was collected to determine the
inflammatory cytokine production. In
addition, we collected the
bronchoalveolar lavage fluid (BALF)
cells from the right lung to determine the
total inflammatory cells and the cell-free
BALF to determine the total BALF protein
concentrations
The lung tissue sections were
stained by immunohistochemistry
with Ly6G antibody to observe
the infiltration of neutrophils in
the lung.

6. 3 Detection of cytokines 4 Western blot
Methods
A laboratory technique used to detect a
specific protein in a blood or tissue sample.
The method involves the use of gel
electrophoresis to separate the proteins in
the sample. These proteins are transferred
from the gel to the surface of a membrane.
The membrane is exposed to a specific
antibody against the protein under study.
They used the ELISA kits for
TNF-α and IL-6 to determine
the plasma TNF-α and IL-6
levels following the
manufacturer’s instructions.

7. In comparison to control mice, alveolar structures were damaged. There
were hyperemia and bleeding foci, a large number of inflammatory cells
infiltrated and gathered in the interstitium, alveolar septum thickened,
alveolar cells swollen and necrotic, alveolar interstitium edema, alveolar
cavity exudation and transparent membrane formation in the LPS- or BLM-
treated mice.
Ivermectin administration at a dose of 1 mg/kg or 2 mg/kg
preserved alveolar structural integrity and reduced alveolar
hemorrhage, inflammatory cell infiltration, and alveolar cavity
exudation.
Results

8. As shown in Fig. 6, LPS or BLM challenge increased lung infiltrated
neutrophils and MPO activity in mice lungs compared to control mice,
whereas ivermectin treatment significantly reduced the neutrophils,
accompanied by decreasing the activity.
In an LPS-induced sepsis model, mice treated with ivermectin given 2 mg/kg
had a more survival rate than mice given 1 and 4 mg/kg [22]. In line with
these findings, ivermectin at a dose of 2 mg/kg had better protective
effects, including improved body weight loss and a decreased death rate in
the LPS- or BLM-induced ALI animals.
In line with these findings, ivermectin at a dose of 2 mg/kg had better
protective effects, including improved body weight loss and a decreased
death rate in the LPS- or BLM-induced ALI animals.
Results

9. As shown in Fig. 8, compared to control mice, LPS or BLM
treatment significantly promoted the degradation of IκBα, an
inhibitor of NF-κB, which could be prevented by ivermectin.
They detected the expression of MAPK and NF-κB signaling
proteins to learn more about the underlying mechanism of
ivermectin’s effect on ALI.
they found that mice treated with LPS or BLM had higher levels of
phosphorylated JNK, Erk1/2, and p38 MAPK than control mice.
However, ivermectin did not affect the Erk1/2 phosphorylation
from LPS- or BLM-treated mice, but it did inhibit p-JNK and p-p38
MAPK expression, indicating that JNK and p38 MAPK signals are
involved in ivermectin’s protective effect on ALI models.
Results

10. Discussion
1 2 3
In a previous study, ivermectin
was demonstrated to inhibit
plasma TNF-α and IL-6 in
mice treated with LPS at a
lethal dose of 32 mg/kg, and
our data further supported
these findings.
X. Zhang.
Ivermectin has also been proven to
have an inhibitory impact on
inflammatory responses in different
animal models. In allergic asthma
models, ivermectin at a dose of 2
mg/kg can attenuate allergies by
preventing inflammatory cell
infiltration and excessive mucus
secretion by airway goblet cells.
S. Yan.
In addition to natural bioactive
compounds from plants that
have anti-inflammatory
properties, many supportive
drugs, such as ivermectin, have
been demonstrated to have
anti-SARS-CoV-2 activity.
A. Biber.

11. Conclusions
In this study was discovered that ivermectin demonstrated strong
antiinflammatory effects against two animal models. It also
inhibited the MPO activity, a neutrophil marker.
In conclusion, the data reported here demonstrate that ivermectin
can mitigate the ALI caused by LPS or BLM in mice. The potential
mechanisms underlying this protective effect may be associated
with reduced inflammatory response. According to current research,
ivermectin could be a potential and promising candidate to treat
acute lung injury or acute respiratory distress syndrome

13. Thanks!!