• 동의생리병리학회지
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• 제22권5호
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• pp.1210-1214
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• 2008

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium (WAAF) on hepatotoxicity caused by acetaminophen (AAP) and acetaldehyde which are regarded as hepatotoxin. Artemisiae Argi Folium was known to have the antibacterial, immune-enhancing, and anticoagulative properties. In Korean Medicine, Artemisiae Argi Folium is supposed to be related with 'liver meridian' according to traditional medical theory. AAP and acetaldehyde reduce the intracellular production of hydrogen peroxide ($H_2O_2$) and nitric oxide (NO) production of human hepatocyte HepG2. The intracellular production of hydrogen peroxide ($H_2O_2$) was measured by dihydrorhodamine 123 (DHR) assay. NO production was measured with Griess test. WAAF increased the production of $H_2O_2$ and NO reduced by AAP and acetaldehyde in HepG2 cells. Therefore, It could be suggested that WAAF has the hepatoprotective activity against AAP and acetaldehyde.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.172-172
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• 1993

Acetaminophen(이하 AAP)은 간의 mixed function oxidase system에 의해 toxic metabolite로 대사되어 간괴사를 일으킨다. 최근에는 지금까지 임상적으로 사용되어온 한약이나 생약의 cytochrome P450의 활성과 간의 glutathion 합성에 미치는 영향에 대한 연구가 활발하게 진행되고 있다. 본 연구에서는 AAP의 간독성을 억제하는 물질을 규명하고자 민간이나 한방에서 보간 또는 해독제로 많이 사용되고 있는 생약을 screening하였다. 그 결과 간의 약물대사 효소계에 엉힝을 미치는 것으로 보고된 강활(Angelica koreana)과 민간이나 한방에서 간질환치료의 목적이나 해독제로 쓰여온 시호(Buplerum falcatum), 토복령(Smilax china) 및 금은화(Lonicera japonica)가 AAP로 유발된 간독성에 미치는 효과를 살펴보았다. 방법: 예비실험을 통해 강활, 시호, 토복령 및 금은화의 MeOH ext.가 AAP로 유도된 간독성에 방어효과가 있음을 확인하고 이를 hexane, ether, ethyl acetate 및 butanol로 계통분획하여 랫트에 전처치한 후 고농도의 AAP를 투여하여 간 손상을 일으키고 혈청중의 효소활성과 지질ㆍcholesterolㆍbilirubin함량 등을 측정하였다.

• 대한약침학회지
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• 제21권4호
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• pp.249-257
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• 2018

Objectives: The hepatotoxicity induced by Acetaminophen (AAP) mostly mediated by effect on oxidative stress parameters. The Zataria multiflora (Z.M) is an herbal medicine with well-known antioxidant effect. The aim of this study is investigation of preventive effects of Z.M and Carvacrol (CAR) on AAP-induced hepatotoxicity in rats. Methods: Rats were randomly divided into four groups including: 1) Control, 2) Acetaminophen (AAP), 3) and 4) CAR. The saline, Z.M (200 mg/kg) and CAR (20 mg/kg) were administrated orally for 6 days, after that AAP (600 mg/kg) was administrated in the $7^{th}$ day. Blood sampling was performed on the first and last days. Also, the liver tissue was removed for evaluation of Malondyaldehide (MDA), Thiol content, Superoxide dismutase (SOD) and Catalase (CAT). Total Protein (tPro), Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP) in liver tissue were evaluated. The changes (${\Delta}$) of enzymes activities were presented. Results: The ${\Delta}GOT$, ${\Delta}GPT$ and ${\Delta}ALP$ in CAR group significantly decreased compared to AAP group (P < 0.01 to P < 0.001) and ${\Delta}GPT$ in Z.M group was significantly reduced in comparison with AAP group (P < 0.05). Also, MDA, Thiol, SOD and CAT levels in treated groups were attenuated compared to AAP group (P < 0.05 to P < 0.001). Conclusion: Z.M and CAR have a powerful hepatoprotective effect. CAR is more effective than Z.M. Based on the results. Z.M and CAR could be potent supplementary agents against hepatotoxicity of AAP in patients.

• 대한임상독성학회지
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• 제9권2호
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• pp.71-76
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• 2011

Purpose: The Rumack-Matthew nomogram cannot be applied in managing overdose by extended release (ER) preparation acetaminophen (AAP). This study analyzed the clinical characteristics of ER preparation AAP overdose in order to develop a treatment recommendation. Methods: We retrospectively reviewed the medical records of patients presented to the emergency department as a result of AAP overdose from Jan 2008 to Dec 2010. Only those patients who ingested an ER preparation of AAP were included in the study. Their blood AAP concentrations were measured at 4 and 8 hours after ingestion. Clinical variables related to AAP intoxication were analyzed. Results: Of the total 108 AAP overdose patients identified during the 3-year period, 20 suffered specifically with ER preparation AAP overdose. The mean estimated ingestion amount was 167.5 mg/kg. Treatments including gastric lavage, activated charcoal, and N-acetyl cysteine (NAC) were performed on 10, 14, and 11 patients, respectively. Hepatotoxicity was diagnosed in only one patient who was then successfully treated with NAC. In another case, blood AAP concentration continued to increase until at least 11-hours after ingestion. Conclusion: This study suggested that blood AAP concentrations associated with ingestion of ER formulations of AAP, may increase in an extended manner. Therefore, multiple sampling and longer periods between samples assessing AAP blood concentration may be required for incidences of extended release overdose.

• 대한한의학회지
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• 제23권3호
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• pp.33-42
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• 2002

Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

• 대한임상독성학회지
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• 제6권1호
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• pp.1-8
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• 2008

Acetaminophen (AAP) overdose can result in potentially serious hepatotoxicity. The ingested dose and time from ingestion to presentation are important prognostic factors. Toxic dose in adult is thought to be at least 10 g or 200 mg/kg. However, early management of acute overdose should be guided by the plasma AAP concentration. The antidote for AAP poisoning is N-acetylcysteine (NAC). It provides complete protection against hepatotoxicity if given within 8 h of acute overdose. If the concentration is above the possible toxicity line as predicted by the Rumack-Matthew nomogram, either the 72-hr oral or the 20-hr intravenous NAC regimen should be administered. NAC is also effective if started late in patients with established hepatic failure. This article summarizes the current consensus of clinical assessment and management for acute AAP overdose.

• Food Science and Biotechnology
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• 제16권6호
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• pp.988-993
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• 2007

The protective effect of the water extract of Fraxinus rhynchophylla leaves (FLE) was determined using an animal model of acetaminophen (AAP)-induced nephrotoxicity. The BALB/c male mice used in this study were divided into 3 groups; the normal, AAP-administered, and FLE-pretreated AAP groups. A single dose of AAP induced necrosis of renal tubules and congestion along with edema to a remarkable degree as observed by hematoxylin and eosin stain, and also increased the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive renal tubular epithelial cells. Blood urea nitrogen and plasma creatinine levels were determined to be significantly higher in the AAP group than in the normal group. However, FLE pretreatment resulted in an attenuation of renal tubule necrosis. Regeneration and dilatation of renal tubules were noted, and the numbers of TUNEL-positive cells were reduced in the FLE-pretreated groups. In an effort to detect the bioactive compounds exerting protective effects in FLE, the analysis of phenolic compounds via gas chromatography/mass spectrometry (GC/MS) were performed, and identified esculetin and esculin. The present study indicates that these compounds may exert a protective effect against AAP-induced nephrotoxicity.

• Archives of Pharmacal Research
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• 제15권3호
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• pp.246-250
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• 1992

Acetaminophen (AAP) and ranitidine (RT) were coadministered orally to nine rats, and the possible contribution of the gastric emptying to the plasma concentration profiles of them was examined. The drugs showed multiple plasma peaks similar to the respective ones after separated administration of each durg. IT Implies that there is no significant interaction between AAP and RT in terms of the gastric emptying or drug absorption. There were no significant linear correlations of the peak patterns (peak height and peak time) between AAP andd RT. It is contrary to the expectation from the biphasic gastric emptying (BGE) theory previously suggested for AAP and RT. The BGE theory. Therefore, seemed to have some draw-backs in explaining satisfactorily the multiple plasma peaks of AAP and RT. Two more doubts raised previously against the BGE theory were also discussed.

• 대한임상독성학회지
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• 제10권2호
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• pp.97-102
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• 2012

Purpose: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. Methods: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. Results: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. Conclusion: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.

• Journal of Pharmaceutical Investigation
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• 제20권1호
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• pp.29-33
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• 1990

Plasma and saliva concentrations of acetaminophen (AAP) were determined at various time points by HPLC after oral administration of AAP tablets (AAP 500 mg) to four healthy male Korean subjects. Saliva concentrations (S) of AAP were significantly correlated with plasma AAP concentrations (P). The S/P ratio of AAP was calculated to be 1.05 (r =0.944, $p<10^{-6}$) for all the data points from the subjects. It showed a little intersubject variation and ranged from 0.89 to 1.46 in each subject. Bioavailability parameters such as AUC, $C_{max}$ and $T_{max}$ which are usually obtained from the plasma concentration data will be predictable approximately by saliva concentration data. Saliva seems to be very convinient and useful samples for the preliminary studies of bioavailability and bioequivalence of AAP preparations, since it can be collected frequently without any painful venipuncture to the subjects, that is inevitable in plasma sampling. Evaluation of the bioavailability of a preparation by saliva samples will reduce the cost, time and safety risk greatly in developing a new drug delivery system for AAP.