Acetyl cysteine amide and cerium oxide nanoparticles as a drug delivery for ischemic stroke treatment: Inflammation and oxidative stress crosstalk

چکیده مقاله

Background: Inflammation and oxidative stress crosstalk is involved in the ischemic stroke(IS) pathogenesis and
the new therapeutic options should be offered based on the targets that are critical in the golden hour of IS. YKL-
40 and total antioxidant capacity(TAC), the inflammation and oxidative stress biomarkers, provide us with clues
for proper intervention targets. N-acetyl cysteine amide (NACA), a lipophilic antioxidant, with a nanoparticlebased
drug delivery system is permeable enough to penetrate blood-brain barrier (BBB) and was proposed as
a new treatment option for IS. In this study, we evaluated the YKL-40 and TAC levels in the sera of IS patients to
elucidate the best intervention target. A rat tissue model is used to assess the NACA efficiency. The microbiology
tests performed to figure out the potential NACA and antibiotics interactions.
Material and methods: The YKL-40 and TAC were measured in the serum of IS patients by ELISA and FRAP
methods, respectively. The serum samples were obtained 12 h after the patient’s admission and meantime other
laboratory findings and NIHSS-based prognosis were recorded. In the animal study, the brain cortex, liver,
kidney, adipose, and the heart of healthy rats were dissected and then incubated in DMEM cell culture media
containing 50 micrograms/milliliter of nanoparticles; the nanoparticles were titanium dioxide nanoparticles
(TiO2 NPs), copper oxide nanoparticles (CuO NPs) and cerium dioxide nanoparticles (CeO2 NPs). Olive oil and
human serum albumin solution were exposed to the nanoparticles with and without NACA. TAC was measured in
the supernatant culture media. With similar concentrations and settings, we evaluated the NACA, nanoparticle,
and antibiotics interactions on pseudomonas aeruginosa.
Results: There was a nonparametric correlation between YKL-40 levels and post stroke serum TAC levels. Nonsmokers
had higher YKL-40 and TAC levels than smokers. A new calculated variable, urea*lymphocyte/age,
predicts a poor prognosis with an acceptable AUC (0.708). Exposing to the nanoparticles, the liver, kidney, and
brain had a significantly higher TAC than adipose and cardiac tissue. The NACA had an ameliorative effect
against TiO2 NPs in the brain. This effectiveness of NACA was also observed against CuO NPs treatment.
However, the CeO2 NPs exert a strong antioxidant property by reducing the TAC in the brain tissue but not the
others. Albumin showed antioxidant properties by itself, but olive oil had an inert behavior. NACA had no
interaction with the action of routine antibiotics.
Conclusion: Oxidative stress but not inflammation is the best point for intervention in IS patients because YKL-40
has not a relationship with NIHSS score. The CeO2 NPs and NACA combination are eligible option to develop
antioxidant-based drug for the treatment of IS. As a complementary finding, the urea*lymphocyte/age is proposed
as a NIHSS-based prognosis biomarker.