• 한국식품영양과학회지
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• 제29권3호
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• pp.448-452
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• 2000

실험동물에서 곰피로부터 분리한 phlorglucinol은 acetaminophen의 투여로 현저히 증가된 간조직에 있어서 지질과선화의 함량을 억제하였다. Acetaminophen 투여에 따른 간 cytochrome P-450, aminopyrine N-deme-thylase 및 aniline hydroxylase 활성변동은 관찰할 수 없었다. 곰피 성분 투여군은 glutathione S-transferase의 활성에서는 대조군의 수준에는 미치지 않으나 효소의 활성이 acetaminophen 단독 투여군보다 현저히 증가되었다. 그리고 간조직중 glutathione의 함량은 phlorglucionl을 전처리군에서 acetaminophen 단독 투여군보다 증가되었다. Glutathione reductase 활성에서는 acetaminophen 투여군은 대조군보다 활성이 감소되었으며, 성분으로 전처리한 군은 acetaminophen 단독 투여군보다 증가 되었다. 따라서 곰피에서 분리한 페놀성화합물인 phloroglucinol은 acetaminophen 투여로 증가되던 지질과 산화함량을 감소시키며, acetaminophen 대사효소활성에서는 glutathione S-transferase의 활성이 증가되어 acetaminophen 의 대사를 촉진시키는 것으로 추정된다.

• 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.

• 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.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.185-188
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• 2004

The purpose of this study is to evaluate the effect of cigarette smoke condensate (CSC) on toxification/detoxification metabolic pathway in primary cultured rat hepatocytes. We measured the activities of cytochrome P450 monooxygenases (CYP450s) and UDP-glucuronyltransferase, sulfotransferase and glutathione-S-transferase in CSC-treated rat hepatocytes. CSC significantly increased the activities of hepatic CYP4501A1 and CYP4501A2 to 7.5 fold and 1.6 fold respectively, compared with control level. However, CSC did not affect the activities of conjugation enzymes. We a1so examined if treatment of CSC could change thc cytotoxicity of acetaminophen (AA) through modulation of metabolizing enzymes. In rat hepatocytes, pretreatment with CSC potentiated the cytotoxicity of AA. This result indicates that potentiation of AA toxicity by CSC pretreatment may be related to induction of CYP4501A1 and CYP4501A2.

• Natural Product Sciences
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• 제10권4호
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• pp.182-189
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• 2004

To find the action mechanism of the MeOH extract (LFS) of Ligularia fischeri var. spiciformis herbs (Compositae) and its active component, 3,4-dicaffeoylquinic acid (DCQA) on antihepatotoxicity, the effect was investigated on hepatic lipid perxodation and drug-metabolizing enzyme activities in acetaminophen-treated rat. Pretreatment with 250 mg/kg LFS (p.o.) and 10 mg/kg DCQA (p.o.) significantly decreased hepatic lipid peroxidation caused by acetaminophen injection. Further, LFS and DCQA inhibited hepatic microsomal enzyme activation such as hepatic P-450 cytochrome $b_5$, aniline hydroxylase and aminopyrine N-demethylase, suggesting that the two substances might effectively prevent the metabolic activation or scavenge electrophilic intermediates capable of causing hepatotoxicity. Both LFS and DCQA increased hepatic glutathione content and glutathione reductase activity, indicating that both resultantly prevented hepatotoxicity via antioxidative mechanism. Therefore, it was found that LFS had antihepatotoxicity based on the antioxidative action of DCQA.

• Toxicological Research
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• 제14권2호
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• pp.151-156
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• 1998

Acetaminophen (APAP) and gentamicin are widely used for many patients, but little in-formation is available regarding the combined effects of APAP and gentamicin. This study was aimed to investigate the potent nephrotoxicity following combined-treatment with APAP and gentamicin. Serum biochemical parameters and histopathological changes in the kidney were observed in female SD rats after continuous daily treatment with either 600 mg/kg/day APAP, and/or 300 mg/kg/day gentamicin for 3 days, and compared with saline sham-treated control animals. APAP and gentamicin combination-treated rats exhibited inconsistent increasing tendency in blood urea nitrogen (BUN) by 96 hours after the last treatment, compared to control or the animals treated with each drug. The relative kidney weights were also increased. Histopathological findings of kidneys revealed that necrosis of proximal convoluted tubules were higher in rats treated with APAP and gentamicin combination than the rats treated with each drug alone. These results suggest that combination use of both drugs have more severe nephrotoxicity than treating each drug alone.

• The Korean Journal of Pain
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• 제35권3호
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• pp.271-279
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• 2022

Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

• 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.

• 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.

• 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.