• Herbal Formula Science
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• v.12 no.2
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• pp.139-154
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• 2004

Acetaminophen은 세계적으로 널리 사용되는 해열 진통제이지만, 또한 과용 및 남용, 알코올 중독과 같은 여러 원인에 의해 간독성을 유발할 수 있는 약물이다. 이러한 acetaminophen의 간독성은 CYP에 의해 생성되는 대사산물인 NAPQI와 활성산소에 의해 유발되는 것으로 알려져 있다. 본 연구에서 5주된 수컷 백서에 acetaminophen (500 mg/kg)을 투여하기 전에 대시호탕 (500 mg/kg)를 일주일간 투여하였다. 이후 GOT, GPT, GST 그리고, 조직사진으로 대시호탕의 간보호작용을 측정하였다. 또한 대시호탕의 간보호작용 기전을 항산화작용과 CYP 2E1 발현조절을 통한 NAPQI 생성억제의 두 가지 면에서 측정하였다. GOT, GPT 그리고 조직사진에서 나타난 결과들은 대시호탕이 고용량의 acetaminophen에 대한 간보호작용이 있음을 증명할 수 있었다. 또한 LPO와 catalase, 그리고 GSH 실험에서 나타난 결과들을 통해 대시호탕이 항산화작용이 있음을 알 수 있었다. 그리고 GSH, GST, RT-PCR, western blot 실험에서 대시호탕이 CYP 2E1의 발현을 조절하여 NAPQI 생성을 억제한다는 것도 알 수 있었다. 이상의 결과들을 바탕으로 대시호탕은 항산화작용에 의한 활성산소 제거력과 CYP 2E1의 발현조절을 통한 NAPQI 생성억제로 고용량 acetaminophen에 의해 유도된 간손상에 대해 유의성 있는 보호작용을 한다는 것을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• v.32 no.11
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• pp.1447-1453
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• 2022

Prohibitin 1 (Phb1) is a pleiotropic protein, located mainly in the mitochondrial inner membrane and involved in the regulation of cell proliferation and the stabilization of mitochondrial protein. Acetaminophen (APAP) is one of the most commonly used over-the-counter analgesics worldwide. However, at high dose, the accumulation of N-acetyl-p-benzoquinone imine (NAPQI) can lead to APAP-induced hepatotoxicity. In this study, we sought to understand the regulation of mRNA expression in relation to APAP and GSH metabolism by Phb1 in normal mouse AML12 hepatocytes. We used two different Phb1 silencing levels: high-efficiency (HE, >90%) and low-efficiency (LE, 50-60%). In addition, the siRNA-transfected cells were further pretreated with 0.5 mM of Sadenosylmethionine (SAMe) for 24 h before treatment with APAP at different doses (1-2 mM) for 24 h. The expression of APAP metabolism-related and antioxidant genes such as Cyp2e1 and Ugt1a1 were increased during SAMe pretreatment. Moreover, SAMe increased intracellular GSH concentration and it was maintained after APAP treatment. To sum up, Phb1 silencing and APAP treatment impaired the metabolism of APAP in hepatocytes, and SAMe exerted a protective effect against hepatotoxicity by upregulating antioxidant genes.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.455-460
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• 2009

Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

• Journal of Food Hygiene and Safety
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• v.13 no.3
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• pp.258-267
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• 1998

The acetaminophen (AP AP), an antipyretic and analgesic agent, induces the hepatotoxicity by increasing influx of calcium and destabilizing the cellular membrane which can be caused by N-acetyl-p-benzoquinoneimine generated by cytochrome P-450 (CYF-450) when it is overdosed. Diltiazem (DIL), a calcium channel blocking agent, has been known to suppress the CYF-450 activities. To study the effect of DIL in APAP treated rats, the serum biotransformational enzyme analyses and the liver histopathologic examination were conducted on the rats which had been administered DIL at 3, 6, 9 and 12 hours after the 3,000 mg/kg of APAP administration. Following a single dose of DIL administered 12 hours after AP AP administration, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, malondialdehyde and calcium contents of liver and microsome were significantly reduced. Glutathione S-transferase (GST) activity was significantly increased. Histopathologic studies showed that DIL had prevented the development of centrilobular necrosis induced by AP AP in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radical and the influx of calcium and could increase GST activity. Therefore, diltiazem can be administered at the time of 12 hours after overdosed AP AP to diminish the liver damage.