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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 10 - 19 (10page)
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초록· 키워드
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Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP induced hepatotoxicity and investigate the underlying mechanisms for the first time.
Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250mg/kgAPAP exhibited severe liver injury after 24h, and hepatotoxicity was assessed.
Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group.
Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.
Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250mg/kgAPAP exhibited severe liver injury after 24h, and hepatotoxicity was assessed.
Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group.
Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.
목차
ABSTRACT
1. Introduction
2. Materials and methods
3. Results
4. Discussion
References
참고문헌 (56)
참고문헌 신청
Zamora Nava LE / 2014 / Acute-onchronic liver failure : a review / Ther Clin Risk Manag 10:295~303
Sun H / 2011 / The protective role of hydrogen-rich saline in experimental liver injury in mice / J Hepatol 54:471~480
Dargan P / 2002 / Paracetamol : balancing risk against benefit / QJM 95:831~832
He M / 2012 / Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice / Food Chem Toxicol 50:3142~3149
Larson AM / 2007 / Acetaminophen hepatotoxicity / Clin Liver Dis 11:525~548
Sun H / 2011 / The protective role of hydrogen-rich saline in experimental liver injury in mice / J Hepatol 54:471~480
Dargan P / 2002 / Paracetamol : balancing risk against benefit / QJM 95:831~832
He M / 2012 / Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice / Food Chem Toxicol 50:3142~3149
Larson AM / 2007 / Acetaminophen hepatotoxicity / Clin Liver Dis 11:525~548
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UCI(KEPA) : I410-ECN-0101-2019-524-000425323