• 셀메드
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• 제4권3호
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• pp.18.1-18.5
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• 2014

Leea asiatica (L.) Ridsdale, a folk medicinal plant is used by the ethnic people of North East India for the treatment of hepatic disorder. In this study, we have investigated the hepatoprotective and antioxidant activity of L. asiatica leaves against acetaminophen induced hepatotoxicity. Methanol extract of L. asiatica (150 and 300 mg/kg/day, p.o.) were administered to rats for three consecutive days followed by single acetaminophen (3000 mg/kg, p.o.) administration on $3^{rd}$ day. After 48 h of acetaminophen administration animals were sacrificed and biochemical estimation of serum, in vivo antioxidant activity using liver tissue were carried out. High levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol and triglycerides were observed in disease control group, which found near to normal in extract treated groups. Higher dose exhibited significant hepatoprotective activity against acetaminophen induced toxicity. Level of superoxide dismutase, catalase, glutathione peroxidase in liver tissue, and reduced glutathione in liver and blood were also significantly increased in extract (300 mg/kg) treated animals compare to disease control group. In this study we found that leaves of L. asiatica exhibited potent hepatoprotective activity against acetaminophen induced hepatic damage in experimental animals which justify the folklore claim, and the possible mechanism of this activity may be due to strong antioxidant activities of extract.

• Biomolecules & Therapeutics
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• 제2권1호
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• pp.47-53
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• 1994

The methylation response as well as the level of methyl donor substance, 5-adenosyl-L-methionine (SAM) has been suggested to be related to hepatotoxicity including hepatocarcinogenesis. But direct correlation between protein methylation and hepatotoxicity has not been established to the present. To observe relationship between protein methylation and short-term hepatotoxicity induced by chemical substances, the activities of protein methylase I and II (PM I, PM II) were examined in cytosolic fraction of SD rat treated orally with acetaminophen(AA), $\alpha$-naphtyl-isothiocyanate (ANIT) and tetracycline (TC) that was known to produce necrosis, cholestasis and steatosis respectively. To evaluate the degree of hepatotoxicity induced by each chemicals, we observed the serum levels of indicative parameters and histopathological alteration. In AA treated group, the activities of PM I were increased at 6, 12 hours after administration, prior to the appearance of the hepatotoxicity by clinical parameters. It was suggested that the levels of PM I were related with the initial stage of hepatotoxic mechanism induced by AA. In ANIT treated group, though most of clinical parameters were significantly increased at 24, 48 hours after administration, the activity of PM I was not changed, indicating that ANIT induced hepatotoxicity was not coupled to protein methylation.

• 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.

• 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.

• 약학회지
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• 제42권6호
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• Advances in Traditional Medicine
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• 제10권1호
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• pp.29-36
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• 2010

The present study was aimed to investigate the hepatoprotective and antioxidant activities of ethanol extract from Monochoria vaginalis (250 mg/kg and 500 mg/kg B/W) on acetaminophen (APAP) induced rat hepatic injury. Monochoria vaginalis is a traditional medicinal plant that is commonly used to treat and improve liver conditions in India and other Asian countries. The development of hepatotoxicity induced by APAP is promoted by oxidative stress. APAP treated group significantly (P < 0.01) elevated the serum enzymatic levels like glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase (SALP), total bilirubin and malondialdehyde (MDA), which were restored towards normalization significantly (P < 0.01) thanol extract of yonochoria vagin is (EEMV). In addition, the EEMV significantly (P < 0.01) elevated the decreased level of total protein and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase and reduced glutathione. Apart from these, histopathological changes also showed the protective nature of the EEMV against APAP induced hepatic damage in liver tissues. The activity of EEMV at 500 mg/kg B/W was comparable to the standard drug silymarin (25 mg/kg B/W). In conclusion, these data suggest that the EEMV possess hepatoprotective and antioxidant effects against APAP-induced hepatotoxicity and oxidative stress in rats.

• 약학회지
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• 제40권5호
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• pp.574-581
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• 1996

The study was initiated to elucidate the protective mechanism by examining in vivo effect of some marine natural products, Styela plicata, Ecklonia stolonifera and Pachymeniopsis elliptica on acetaminophen-induced lipid peroxidation. The methanol extract of S. plicata prevented acetaminophen (800mg/kg, i.p.)-induced hepatotoxicity in rats as evidenced by the decreased formation of lipid peroxide. But the methanol extracts of E. stolonifera and P. elliptica were not affected on the formation of lipid peroxidation. The activities of cytochrome P-450, animopyrine N-demethylase and aniline hydroxylase were not changed by the treatment with S. plicata in comparison with acetaminophen-teated group. In acetaminophen-treated control rats, the glutathione S-transferase activity was decreased markably. However. in S. plicata pretreated group, the effect caused by acetaminophen was markably reduced. A-cetaminophen decreased the level of hepatic, glutathione, which was restored to same degree by S. plicata pretreatment. And activity of ${\gamma}$-glutamylcystein synthetase was not changed by S. plicata pretreatment, but the activity of glutathione reductase was increased significantly.

• 대한본초학회지
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• 제22권1호
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• pp.1-6
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• 2007

Objectives : The purpose of this study is that the protective effects of habmayou on acetaminophen (AP)-induced hepatotoxicity were investigated in mice. Methods : Before administering AP mice supplied with only water were left alone for 18 hours. after concentration and dissolution in poly ethylglycol AP 400mg per 1kg of mouse weight, we injected AP titrated density with a physiological saline solution into the abdominal cavity of mouse to induce hepatotoxicity. we researched mortality rate and the shape of liver tissue of mouse. Results : Treatment with habmayou (250 mg/kg, p.o.) 0.5 h after AP administration significantly prevented an increase in plasma alanine aminotransferase and aspartate aminotransferase activities and AP-induced hepatic necrosis, and also reduced AP-induced mortality from 46% to 0%. In addition, oral treatment with habmayou significantly prevented AP-induced depletion of glutathione (GSH) contents. However, habmayou treatment, by itself, did not affect hepatic GSH contents. Conclusion : These results show that the hepatoprotective effects of habmayou against AP overdose may be due to its ability to block the bioactivation of AP by regeneration of hepatonecrotic cells.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.331-337
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• 2008

This study was conducted to quantitatively evaluate the recovery effects of herbal medicines on acetaminophen-induced hepatotoxicity. In the present study, the recovery effects of 251 herbal medicines on THLE-2 cells that had been damaged by acetaminophen were evaluated using an MTS assay. THLE-2 cells were cultured in 96-well plates and then pretreated with or without 60 ${\mu}M$ acetaminophen (${IC}_{50}$ value: 35.84) for 1 hr. Next, different herbal medicines were added to the wells, after which the cells were reincubated at $37^{\circ}C$ for 24 hr. After first round of screening, the candidate herbal medicines were selected based on a recovery rate of greater than 40% and their efficacy were then determined by dose response kinetic analysis. Among these extracts, 8 herbal medicines (Terminalia chebula, Pueraria lobata, Acronychia laurifolia, Lopatherum gracile, Oroxylum indicum, Cynanchum atratum, Senecio scandens, and Sophora flavescens) had a strong recovery effect on acetaminophen-induced damage in THLE-2 cells. Dose response non-linear regression analysis demonstrated that Senecio scandens showed the best recovery rate (98%), and that its ${EC}_{50}$ was 19.54 ng/mL. Additional studies of these herbal medicines should be conducted to determine if they possess novel therapeutic agents for the prevention or treatment of liver disorders.