Sasa veitchii extracts suppress acetaminophen-induced hepatotoxicity in mice
Yoshioka et al. Environmental Health and Preventive Medicine
Sasa veitchii extracts suppress acetaminophen-induced hepatotoxicity in mice
Hiroki Yoshioka 0
Haruki Usuda 1
Hirohisa Fujii 0
Tsunemasa Nonogaki 0
0 College of Pharmacy, Kinjo Gakuin University , 2-1723 Omori, Moriyamaku, Nagoya, Aichi 463-8521 , Japan
1 Department of Pharmacology, Shimane University Faculty of Medicine , 89-1 Enya-cho, Izumo, Shimane 693-8501 , Japan
Background: The aim of this study was to investigate the therapeutic effects of a Sasa veitchii leaf extract (SE) on acetaminophen (APAP)-induced hepatotoxicity. Methods: Seven-week-old male ddY mice were orally administered SE or saline (0.2 mL) once a day for a week. Twenty-four hours after the last pretreatment, the mice were intraperitoneally injected with 550 mg/kg APAP or saline under fasting conditions. The mice from each group were euthanized and bled for plasma analysis 2, 6, 24, and 72 h after the injection. Results: We found that pretreatment with SE significantly decreased hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase), oxidative stress (malondialdehyde and glutathione level), inflammatory cytokines, histological damage, c-jun N-terminal kinase activation, and receptor-interacting protein-1 activation. Further, SE pretreatment decreased Cyp2e1 expression and increased total antioxidant capacity in the liver. Conclusion: Our findings demonstrate that prophylactic SE treatment protects mice from APAP-induced hepatotoxicity through modulation of Cyp2e1 expression and antioxidant capacity.
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Background
Bamboo leaves have been extensively used in folk
medicine as an antifebrile and antihypertensive medication
for centuries [1, 2]. In addition, in Japan, due to their
antimicrobial activity, bamboo leaves have been used to
wrap sushi sheets to protect against bacterial spoilage.
Recently, extracts of bamboo leaves were reported to
have multiple biological activities including antioxidant
activity and cancer prevention [3, 4]. Furthermore,
previous studies have demonstrated the antitumor [5],
antioxidant [1, 6], antiviral [7], anti-inflammatory [8], and
anti-allergic [9] activities of the extract.
The liver is most vulnerable to attack by chemical
toxic agents since it is one of the most internal organs
with multiple functions such as detoxification and
protein synthesis [10, 11]. Therefore, liver diseases are
among the most serious health problems worldwide.
Our previous investigation found that Sasa veitchii leaf
extract (SE) prevented carbon tetrachloride
(CCl4)-induced hepatotoxicity in mice [12], suggesting that SE
might maintain liver homeostasis. Although CCl4 is
commonly used in animal models to study chemical
toxin-induced liver injury [13, 14], exposure to CCl4
does not reflect a real-life scenario. The most common
etiologies of liver damage in real life are acute viral
hepatitis A and B, drug-related liver injury, and the
alcohol-acetaminophen syndrome (AAS). In terms of
drug-related liver injury, acetaminophen (APAP) is well
known. In addition, the main cause of acute liver failure
in industrialized countries is APAP overdose. APAP is
recognized as a popular analgesic and antipyretic drug at
therapeutic doses. However, APAP can cause severe liver
injury in animals and humans through its side effects
[15]. The main mechanism of APAP-induced
hepatotoxicity has been studied in detail [16–19] and occurs
in multiple steps. First, APAP is majority metabolized by
Cyp2e1 and minority by Cyp1a2. Cyp2e1 is the main Cyp
enzyme that bio-activates APAP at low doses [16, 20]. In
contrast, at a high dose, Cyp1a2 was shown to contribute
to the bio-activation and toxicity of APAP [21].
Cyp© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
produced N-acetyl-p-benzoquinone imine (NAPQI)
depletes glutathione (GSH) and covalently binds to proteins.
Loss of GSH then permits increased formation of reactive
oxygen and nitrogen species. As a result, oxidative stress
is increased, leading to alterations in calcium homeostasis
and initiation of signal transduction responses causing
mitochondrial permeability transition. Mitochondrial
permeability transition causes additional oxidative stress and
inhibits ATP synthesis. Insufficient ATP triggers cell
necrosis. Peripheral to these essential events, a number of
inflammatory mediators such as cytokines and chemokines
are induced that can modify toxicit (...truncated)