@article {647, title = {Protective Effects of Natsumikan (Citrus natsudaidai) Extract on Acetaminophen-induced Lethal Hepatotoxicity in Mice}, journal = {Pharmacognosy Research}, volume = {4}, year = {2012}, month = {October ,2012}, pages = { 234-236}, type = {Short Communication}, chapter = {234}, abstract = {

Background: Like other citrus fruits, natsumikan (Citrus natsudaidai ) contains several antioxidative nutrients which occur in higher concentrations in the peel than in the pulp. A high dose of acetaminophen (APAP) generates highly reactive intermediates and causes fatal liver injury. In this study, we examined whether an extract from immature natsumikan peel prevents lethal hepatotoxicity induced by a lethal dose of APAP in mice. Materials and Methods: Male ICR mice were treated orally with natsumikan extract (300 and 1,000 mg/kg) 2, 26, and 50 hr before single oral APAP (300 mg/kg) administration. Mice were fasted for 18 hr before APAP treatment, but given tap water ad libitum. Survival was assessed for 24 hr after APAP treatment. Results: Following administration of 300 mg/kg APAP, all mice died within 6 h. However, pretreatment with natsumikan extract (300 and 1,000 mg/kg) or silymarin (300 and 1,000 mg/kg) increased the survival rate to 16.7\%, 33.3\%, 16.7\%, and 50\%, respectively, at 24 hr. Conclusion: The results suggest that natsumikan has a protective effect on APAP-induced lethal hepatotoxicity.

}, keywords = {acetaminophen (APAP), Hepatoprotective effect, lethal hepatotoxicity, Natsumikan}, doi = {10.4103/0974-8490.102274}, author = {Katsunori Yamaura and Noriyuki Nakayama and Maki Shimada and Koichi Ueno} } @article {889, title = {Protective Effects of Goldenseal (Hydrastis canadensis L.) on Acetaminophen-induced Hepatotoxicity through Inhibition of CYP2E1 in Rats}, journal = {Pharmacognosy Research}, volume = {3}, year = {2011}, month = {November,2011}, pages = {250-255}, type = {Original Article}, chapter = {250}, abstract = {

Background: Goldenseal (Hydrastis canadensis L.) inhibits various cytochrome P450 (CYP) isoforms such as CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A in vitro. High doses of acetaminophen (APAP) generate the highly reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), catalyzed mainly by CYP2E1. The aim of this study was to investigate the hepatoprotective effects of orally administrated goldenseal against APAP-induced acute liver failure (ALF) via inhibition of CYP2E1. Materials and Methods: Male Wistar rats were treated orally with goldenseal (300 and 1000 mg/ kg) 2, 18, and 26 h before and 6 hr\ after oral APAP (400 mg/kg) administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as serum APAP concentration were evaluated. Results: Goldenseal extract inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A activity, and the inhibitory effect on CYP2E1 was the strongest (IC50 4.32 μg/mL). Treatment with goldenseal (300 mg/kg) significantly attenuated the APAP-induced increase in serum AST and ALT, and the hepatoprotective effect of goldenseal was stronger than that of silymarin (200 mg/kg). Moreover, serum APAP concentration was increased by goldenseal treatment, presumably as a result of the inhibitory effect of goldenseal on the metabolism of APAP to NAPQI. Conclusion: These results suggest that goldenseal ameliorates APAP-induced ALF and that this protection can likely be attributed to the inhibition of CYP2E1 activity, which generates the highly reactive intermediate of APAP.

}, keywords = {Acetaminophen, acute liver failure, CYP2E1, Goldenseal, Hepatoprotective effect}, doi = {10.4103/0974-8490.89745}, author = {Katsunori Yamaura and Maki Shimada and Noriyuki Nakayama and Koichi Ueno} }