• Toxicological Research
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• 제13권3호
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• pp.197-202
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• 1997

Kyoaesamultang(KAT) has been used as an important prescription for various diseases including threatened abortion, associated with pregnancy in traditional medicine. In oder to identify the safety of KAT, this study was designed to determine mutagenicity and hepato-toxicity. In Rec-assay, Bacillus subtills H-17($Rec{^+}$) and M-45($Rec{^-}$) strains were used to clarify the DNA damage property. In Ames test, Salmonella typhimurium TA98 and TA100 were used for mutagenicity testing. In SOS umu test, Salmonella typhimurium TA1535 containing plasmid pSK1002 was used as a tester strain, and the levels of umu operon expression were monitored by measuring the $\beta$-galactosidase activity. From tested results, KAT did not show DNA damage and mutagenicity. On the other hand, hepato-toxicity of KAT to female ICR mice was monitored by the measurements of s-GOT, s-GPT and LDH activities after oral feeding for 15days. KAT showed 34% increase of s-GOT and s-GPT activities, also exhibited 35% increase of LDH activity in mice sera.

• BMB Reports
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• 제40권6호
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Journal of Ginseng Research
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• 제24권2호
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• pp.94-98
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• 2000

Tetracycline hydrochloride (TC) caused 100%, 50% and 20% mortality rates among rats injected with 40 mg, 30 mg and 20 mg/100g. b.w. respectively; while the morta]ity rates were decreased to 50%, 20% and 10% when Panax ginseng (2 mg/100g. b.w.) injected with TC during 72 hrs. post-injection. Subacute-toxicity study demonstrated that TC caused severe hepato-nephrotoxicity (demonstrated by biochemical analysis of serum including: transferases , alkaline phosphatase, total protein, glucose, cholesterol urea and creatinine) in rats injected i.p. with 10 mg and 5 mg/100g. b.w. for 7 days of daily injection . These signes of toxicity were greatly diminished by P. ginseng addition to TC doses.

• Toxicological Research
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• 제5권1호
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• pp.1-7
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• 1989

Toxic effects of a mushroom, Amanita volvata, were studied in respect to biochemical and histological changes induced in the liver and kidneys of mice. The changes in biochemical parameters characteristically appeared 12 hrs after oral administration of an aqueous extract of the mushroom. The hepatic glycogen decreased markedly to 17% of the control level and a concemitant decrease in blood glucose was also observed. The activity of serum glutamic oxaloacetic transaminase (SGOT) was elevated by 2.5-fold and the level of blood urea nitrogen (BUN) increased by 3-fold, respectively, 12 hrs after administration of the mushroom, their levels being maintained up to 24 hrs.

• 대한임상독성학회지
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• 제12권1호
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• pp.14-21
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• 2014

Purpose: The objective of this study was to develop a new scoring tool that is comprehensively applicable and predicts fatality within 24 h of intoxication. Methods: This was a cohort study conducted in two emergency medical centers from 2011 to 2012. We identified factors associated with severe/fatality. Through a discriminant analysis, we devised the aBIG (age, Base deficit, Infection, and Glasgow coma scale) score. To compare the ability of aBIG to predict intoxication severity with that of previous scoring systems such as APACHE II, MODS, SAPS IIe, and SOFA, we determined the receiver operating characteristic curves of each variable in predicting severe-to-fatal toxicity. Results: Compared with the mild/moderate toxicity group (n=211), the severe/fatal group (n=143) had higher incidences of metabolic acidosis, infection, serious mental change, QTc prolongation and hepato-renal failure. Age, base deficit, infection-WBC count, and Glasgow Coma Scale were independently associated with severe/fatal poisoning. These variables were combined into the poisoning "aBIG" score [$0.28{\times}$Age group+$0.38{\times}WBC$ count/$10^3+0.52{\times}$Base deficit+$0.64{\times}$(15-GCS)], which were each calculated to have an area under the curve of 0.904 (95% confidence interval: 0.868-0.933). The aBIG poisoning score had an equivalent level of severity predictability as APACHE II and a superior than MODS, SOFA, and SAPS IIe. Conclusion: We developed a simplified scoring system using the four variables of age, base deficit, infected leukocytosis, and GCS. The poisoning aBIG score was a simple method that could be performed rapidly on admission to evaluate severity of illness and predict fatal severity in patients with acute intoxications.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.781-789
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• 2004

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzy-loxyresorufin- and pentoxyresorufin-D-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioace-tamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepato-toxicity and immunotoxicity.

• Nutrition Research and Practice
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• 제12권6호
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• pp.535-540
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• 2018

BACKGROUND/OBJECTIVES: Propolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats. MATERIALS/METHODS: Six groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin. RESULTS: Paracetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss. CONCLUSIONS: Propolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

• 약학회지
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• 제37권5호
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• pp.499-503
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• 1993

Betaine, a major component of Lycii Fructus, was evaluated for its anti-hepatotoxic activity on carbon tetrachloride-induced hepatotoxicity in primary cultured rat hepatocytes. Betaine was found to attenuate carbon tetrachloride-induced hepatotoxicity both morphologically and biochemically. Typical hepatocyte necrosis due to carbon tetrachloride seemed to be reduced by 50 to 500 $\mu{M}$ of betaine under microscopical observation. The value of glutamic pyruvic transaminase released from the hepatocytes into the medium significantly decreased as betaine concentration increased. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride-induced hepatotoxicity. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride.

• Toxicological Research
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• 제13권3호
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• pp.193-196
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• 1997

Matricaria Chammomillal L., Foemiculum Vulgare mill, and Plantago Psylium L. have been screened for their hepato protective activities against liver damge induced by $CCl_4$ intoxication in mice. Hydroalcoholic extractions (2:8) of herbal drugs were concentrated in vacuo and concentrated crude extracts of Matrica Chammomilla L. and Foeniculum Vulgare mill were orally administered at doses of 100 mg/kg, 200 mg/kg, 400 mg/kg, and 800 mg/kg. Plantago Psyllium was given at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg. Liver protective activities of these herbs were determined after administration of $CCl_4$ Liver size, serum enzyme activities, sleeping time, and histopatology of the liver were examined one hour after administration of $CCl_4$. ALT and AST activities, liver weight and sleeping time decreased in groups that received 400 mg/kg of Matricaria Chammomilla L. or Foeniculum Vulgare. Histological investigation showed significant increase in hepatic cell regeneration and reduction in liver injury. The group that received 100 mg/kg Plantago Psylium showed liver protection but protection was not significant in other doses.

• Advances in Traditional Medicine
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• 제9권3호
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• pp.225-231
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• 2009

The present study deals with the amelioration by Lagerstroemia speciosa Linn. leaf extract against hepatotoxicity induced by carbon tetrachloride ($CCl_4$), which was evaluated in terms of serum marker enzymes like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, serum total bilirubin, total protein levels along with concomitant hepatic and antioxidants like superoxide dismutase, catalase, glutathione, glutathione peroxidase and lipid peroxidation enzymes were monitored. These biochemical parameters altered by the single dose level of $CCl_4$ (0.75 ml/kg body weight, i.p). Pre treatment with L. speciosa prior to the administration of $CCl_4$, at the doses of 50 and 250 mg/kg. body weight/day, p.o. for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels, respectively. Silymarin was used as a reference standard, prior to the administration of $CCl_4$ to rats. These findings indicate the protective potential of L. speciosa against hepato toxicity which possibly involve mechanism related to its ability of selective inhibitors of (reactive oxygen species like antioxidants brought about significant inhibition of TBARS suggesting possible involvement of $O_2{\cdot}-$, $HO_2{\cdot}$, and ${\cdot}OH$. In conclusion, the amelioration may be attributed to the synergistic effects of its constituents rather than to any single factor as the leaves are rich in tannins, sterols, flavonoids, saponins etc.