Journal of The Korean Society of Clinical Toxicology

The Protective Effect of Green Tea Extract on Alpha-amanitin Induced Hepatotoxicity: Su Hwan An, Kyung Hoon Sun, Ran Hong, Byoung Rai Lee, Yongjin Park; J Korean Soc Clin Toxicol. 2019;17(2):58-65. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.58

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Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

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Effects of herbal and mushroom formulations used in Traditional Chinese Medicine on in vitro human cancer cell lines at the preclinical level: An empirical review of the cell killing mechanisms
Qiulan Wu, Tingting Dai, Jie Song, Xiaorong Liu, Shaomin Song, Lili Li, Jingbing Liu, Arivalagan Pugazhendhi, Joe Antony Jacob
Process Biochemistry.2020; 94: 136. CrossRef

The Effect of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity in a Murine Model: Chang Yeon Ryu, Kyung Hoon Sun, Ran Hong, Yongjin Park; J Korean Soc Clin Toxicol. 2018;16(2):108-115. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.108

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Abstract PDF: Purpose: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on${alpha}$-amanitin-induced hepatotoxicity have been published. ${alpha}$-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that ${alpha}$-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on ${alpha}$-amanitin-induced hepatotoxicity in a murine model. Methods: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving ${alpha}$-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. Results: GLEA significantly improved the beneficial functional parameters in ${alpha}$-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with ${alpha}$-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. Conclusion: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after ${alpha}$-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.

In vitro Protective Effects of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity: Bo Hyun Kim, Kyung Hoon Sun, Sun Pyo Kim, Yongjin Park; J Korean Soc Clin Toxicol. 2017;15(2):107-115. Published online December 31, 2017; DOI: https://doi.org/10.22537/jksct.2017.15.2.107

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Abstract PDF: Purpose: Glehnia littoralis has been used to treat ischemic stroke, phlegm, cough, systemic paralysis, antipyretics and neuralgia. The pharmacological mechanisms of Glehnia littoralis include calcium channel block, coumarin derivatives, anticoagulation, anti-convulsive effect, as well as anti-oxidant and anti-inflammatory effects. Alpha-amanitin (${alpha}$-amanitin) is a major toxin from extremely poisonous Amanita fungi. Oxidative stress, which may contribute to severe hepatotoxicity was induced by ${alpha}$-amanitin. The aim of this study was to investigate whether Glehnia littoralis ethyl acetate extract (GLEA) has the protective antioxidant effects on ${alpha}$-amanitin -induced hepatotoxicity. Methods: Human hepatoma cell line HepG2 cells were pretreated in the presence or absence of GLEA (50, 100 and $200{mu}g/ml$) for 4 hours, then exposed to $60{mu}mol/L$ of${alpha}$-amanitin for an additional 4 hours. Cell viability was evaluated using the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined. Results: GLEA (50, 100 and $200{mu}g/ml$) significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. GLEA could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells. Conclusion: In the in vitro model, Glehnia littoralis was effective in limiting hepatic injury after ${alpha}$-amanitin poisoning. Its antioxidant effect is attenuated by antidotal therapy.

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