• 한국식품영양과학회지
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• 제26권6호
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

• 동의생리병리학회지
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• 제20권2호
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• pp.410-413
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• 2006

This study was done to investigate the protective effects of Iljungbogan-Tang on acute hepatotoxicity of rats induced by $CCL_4$ and acetaminophen. The subject animals were divided into 3 groups : control group(administrated 0.5% carboxymethyl cellulose), sample group(30, 100, 300, 600mg/kg administrated), positive control group (administrated silymarine), Acute hepatotoxicity of rats were induced by $CCL_4$ and acetaminophen, and the serum transaminase(AST, ALT) were measured for enzyme activities. The inhibitory effects on the serum AST activities were noted in sample group(100, 300, 600mg/kg administrated) on hepatotoxicity of rats induced by $CCL_4$. The inhibitory effects on the serum AST, ALT activities were noted in sample group(30mg/kg administrated) on hepatotoxicity of rats induced by acetaminophen. The inhibitory effects on the serum AST activities were noted in sample group(600mg/kg single dose administrated) on hepatotoxicity of rats induced by acetaminophen. It is considered that Iljungbogan-Tang has protective effects against hepatotoxicity in rats induced by $CCL_4$ and acetaminophen. So it is required to study about the actions of mutual relation of medicines and patho-mechanism through experiment.

• Biomolecules & Therapeutics
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• 제3권3호
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• pp.229-232
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• 1995

In order to study if Glycyrrhizae Radix (GR) has protective effects on hepatotoxicity of acetaminophen in mouse, one of the species which are sensitive to acetaminophen-induced hepatotoxicity, effects of GR on liver weight to body weight ratio, serum alanine and aspartate transaminase (ALT and AST) activities, hepatic UDP-GT2 activity, and histopathologic changes were determined in acetaminophen-treated mice. Liver weight to body weight ratio and UDP-GT2 activity in mouse liver were not altered by GR. However, GR pretreatment lowered serum ALT and AST activities by 77% and 90% respectively, and diminished the degree of centrilobular necrosis caused by acetaminophen in liver as determined by histopathologic observation. These results suggest a possible protective effect of GR against the acetaminophen-induced hepatotoxicity in mice.

• 생약학회지
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• 제36권2호통권141호
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• pp.81-87
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• 2005

The effects of the DWP-04 [DDB:selenium yeast:glutathione (31.1 : 6.8 : 62.1 (w/w%)] on acetaminophen detoxification enzyme system were studied in rats. Treatment with DWP-04 was prevented againt acetaminophen-induiced hepatotoxicity in rat as evidenced by the decreased formation of lipid peroxide. Effect of DWP-04 on the activities of free radical-generating enzymes, free radical scavenging enzymes and glutathione-related enzymes as well as detoxification mechanism of DWP-04 against acetaminophen-treated was investigated in rat. Activities of cytochrome p450, cytochrome b5, aminopyrine demethylase and aniline hydroxylase as free radical-generating enzymes activities were decreased by the treatment with DWP-04 against acetaminophen treated. Although acetaminophen-induced hepatotoxicity results in the significantly decrease in the level of hepatic glutathione and activities of glutathine S-transferase, quinone reductase, glutathione reductase and ${\gamma}-glutamyl-$cysteine synthetase, these decreasing effects were markedly lowered in the DWP-04-treated rat. Therefore, it was concluded that the mechanism for the observed preventive effect of DWP-04 against the acetaminophen-induced hepatotoxicity was associated with the decreased activities in the free radical-generating enzyme system.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.313-322
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• 1995

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

• Toxicological Research
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• 제9권2호
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• pp.133-145
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• 1993

The present study examined the effects of butylated hydroxyanisole (BHA) on acetaminophen (AA)-induced hepatotoxicity in male rats and also examined the effects of these compounds on the biliary excretion of phenolphthalein (PP) and the hepatic glucuronidation. Male Sprague-Da-wley rats were pretreated with BHA (0.75% in diet for 10 days) were given single dose of AA (600mg/kg, ip) and liver function was determined 24 hr later. Serum activity of alanine aminotransferase (ALT) and histopathology were used as indices of hepatotoxicity.

• Toxicological Research
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• 제3권2호
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• pp.121-128
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• 1987

Protective effect of scoparone against the acetaminophen inducible hepatic toxicity in mice was investigated. Scoparone (5mg/kg) was administered intraperitoneally to mice daily for 5 days. Scoparone pretreatment before the administration of acetaminophen has blocked subsequent increases in liver to body weight ratio. When biological changes were measured, scoparone protects against acetaminophen inducible hepatotoxicity in mice as evidenced by the decreased formation of lipid peroxide, lowered serum transaminase activity and the decreased level of serum acetaminophen. In conjuction with the results of Huh (Arch. Pharm. Res. 10, 165(1987)), these results suggest that the most likely mechanism for the observed protective effects of scoparone against the acetaminophen-induced hepatotoxicity is the induction of hepatic microsomal UDP-glucuronyltransferase activity.

• Nutrition Research and Practice
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• 제3권2호
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• pp.95-101
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• 2009

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.

• 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.

• 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.