Sasa veitchii extracts suppress acetaminophen-induced hepatotoxicity in mice

Environmental Health and Preventive Medicine, Jun 2017

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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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. - 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)


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Hiroki Yoshioka, Haruki Usuda, Hirohisa Fujii, Tsunemasa Nonogaki. Sasa veitchii extracts suppress acetaminophen-induced hepatotoxicity in mice, Environmental Health and Preventive Medicine, 2017, pp. 54, Volume 22, Issue 1, DOI: 10.1186/s12199-017-0662-3