Nrf2: The custodian regulating oxidative stress and immunity against acrylamide toxicity
Date:
June 21, 2021
Source:
Tokyo University of Science
Summary:
A study using genetically modified mice shows that a protein
called Nrf2 increases the expression of protective genes in the
acrylamide-induced toxic response.
FULL STORY ========================================================================== Acrylamide, which is extensively used in industries, causes peripheral neuropathy or encephalopathy. Now, scientists from Japan examined the
response against oxidative stress in acrylamide-induced neurotoxicity and
found that nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the immune system and response to oxidative stress, was at
the center of this toxicity. They found that Nrf2 plays a protective
role by increasing the expression of protective genes and decreasing
that of pro-inflammatory genes.
========================================================================== Acrylamide is a toxic chemical compound that affects the nervous
system. Not only is it widely used in industries such as paper production, plastics, and wastewater management, but it is also a byproduct of
commonly used food processing methods, which makes human exposure to
acrylamide inevitable.
Therefore, many studies have focused on understanding the toxic effects
of acrylamide and our body's response to them. Generally, in response to toxicity, the body's cells release protective factors and antioxidants
to remedy the damage. This response is activated by various cellular
machinery. One such activator is a protein called "nuclear factor
erythroid 2-related factor 2" (Nrf2), which is a master regulator of
the response to oxidative stress and the immune system.
In a recent study, a team of scientists, led by Prof. Gaku Ichihara
from Tokyo University of Science, reported the role of Nrf2 in acrylamide-induced neurotoxicity. Prof. Ichihara states, "Our study showed
that Nrf2 has a protective role against neurologic damage and suggests
it is through activation of antioxidant stress genes and suppression of proinflammatory cytokine genes." In their study published in the journal Toxicology, Prof. Gaku Ichihara, along with his colleagues Prof. Masayuki Yamamoto from Tohoku University, Prof. Ken Itoh from Hirosaki University, Associate Prof. Seiichiroh Ohsako from The University of Tokyo, and
Prof. Sahoko Ichihara from Jichi Medical University, used mice models
to study the role of Nrf2 in acrylamide-induced neurotoxicity.
They tested their hypothesis that when Nrf2 gene is removed, the
neurotoxic effects of acrylamide will be amplified. For this, they
developed "knockout" mice that could not produce Nrf2, and gave the Nrf2-knockout mice and a set of counterpart "wild-type" mice that could
produce Nrf2 different concentrations of acrylamide for 4 weeks. Then,
they compared the neurotoxicity between both groups of mice using various sensory and motor tests, immunohistochemistry, and protein and gene
expression analyses.
The scientists found that the Nrf2-knockout mice had severe neurotoxic
effects such as sensory and motor system dysfunction and axonal
damage. While these mice produced fewer antioxidants and protective
factors in response to acrylamide, they also showed enhanced release
of pro-inflammatory chemicals, called "cytokines," in the brain, which
can potentially cause additional damage. Additionally, as different
doses were given to the mice, the scientists also determined that the neurotoxicity was dose-dependent.
Previous studies have established the role of Nrf2 as a master regulator
of protective genes but this study explained the specific mechanisms of
immune response to acrylamide-induced toxicity, with Nrf2 at the center of
it all. As Prof. Ichihara states, "The results document the first known morphological and neuro-functional evidence of the regulatory role of
Nrf2 in acrylamide-induced neurotoxic effects in mice." The findings of
this study are also immensely valuable in the field of disease biology,
as recent studies have shown a link between air pollution and Alzheimer's disease. Since the air contains other acrylamide-like chemical pollutants
with similar neurotoxic effects, the study's findings could prove useful
in the prevention of Alzheimer's disease.
Prof. Ichihara and his team's study is certainly a timely one, as
reports of acrylamide intoxication are on the rise and further research
is required to better understand the specific mechanisms by which the
body protects itself from harm.
========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Frederick Adams Ekuban, Cai Zong, Madoka Takikawa, Kota Morikawa,
Toshihiro Sakurai, Sahoko Ichihara, Ken Itoh, Masayuki Yamamoto,
Seiichiroh Ohsako, Gaku Ichihara. Genetic ablation of Nrf2
exacerbates neurotoxic effects of acrylamide in mice. Toxicology,
2021; 456: 152785 DOI: 10.1016/j.tox.2021.152785 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/06/210621123727.htm
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