• Journal of The Korean Society of Clinical Toxicology
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• v.20 no.2
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• pp.39-44
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• 2022

N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.

• Journal of Convergence Korean Medicine
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• v.5 no.1
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• pp.45-54
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• 2023

Objectives : Alcohol-induced liver disease advances as to reactive oxygen species (ROS) and cellular lipid peroxidation increase. We examined the hepatoprotective effects of Zingiber officinale Roscoe rhizome extract (ZR), Pueraria lobata Ohwi flower extracts (PF), and a newly developed herbal juice (HJ), which was a combination of ZR and PF extracts, against ethanol-induced hepatotoxicity. Methods: The study utilized the human hepatoma cell line HepG2 cells to validate the hepatoprotective effect of HJ (50~200 ㎍/mL) against ethanol (EtOH, 700 mM)-induced liver damage. Results: HJ effectively reduced the protein expression of sterol regulatory element-binding transcription factor 1, adiponectin, and AMP-activated protein kinase in EtOH-induced HepG2 cells. The levels of ROS, total cholesterol, and triglycerides, which are the result of various synthesis and lipogenesis processes induced by EtOH in the liver, were reduced by HJ. Furthermore, the activities of alcohol dehydrogenase and aldehyde dehydrogenase, enzymes linked to alcohol degradation, were more effectively downregulated by HJ treatment compared to treatment with ZR and PF alone, all without causing cytotoxic effects. Conclusions: HJ protects the liver by inhibiting EtOH-induced lipogenesis, lowering ROS generation, and improving alcohol degradation, which is more effective than ZR and PF alone. Further, in vivo experiments can offer additional evidence regarding the effectiveness, safety, and underlying mechanism of action of HJ.

• Journal of Veterinary Science
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• v.24 no.3
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• pp.43.1-43.8
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• 2023

Background: Meloxicam is used widely for exotic animal analgesia, but its toxicity in common raptor species in Thailand is unclear. Objectives: This study evaluated the single-dose effect of intramuscular meloxicam in common raptor species in Thailand for short-term and long-term periods. Methods: Twenty-two raptors were administered a single 1 mg/kg dose of meloxicam individually via intramuscular injection. The following were evaluated: clinical appearance, body weight, body condition score, body temperature, fecal appearance, complete blood cell count, and biochemistry panel before (day 0) and after the injection (1, 7, and 30 days). The collected samples were categorized into three groups: Brahminy kite (Haliastur indus) (n = 10), adult Barn owl (Tyto javanica) (n = 4), and juvenile Barn owl (n = 8). Results: None of the raptors in the study groups showed any abnormalities. The hematological profiles were significantly different in the short-term period (day 1 and day 7). The creatinine, aspartate aminotransferase, and creatinine kinase increased in several groups. On the other hand, the packed cell volume decreased in the Brahminy kite and juvenile Barn owl groups. According to the findings, an intramuscular injection of 1 mg/kg meloxicam affected the blood biochemistry panel of the muscle, but the affected raptors recovered within one week. Conclusions: An intramuscular injection of meloxicam at a single 1 mg/kg dose in Brahminy kites and Barn owls was not associated with the morbidity, hepatotoxicity, gastrointestinal toxicity, and nephrotoxicity in the short- and long-term periods.

• Korean Journal of Agricultural Science
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• v.48 no.4
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• pp.935-944
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• 2021

It has been suggested that bisphenol A (BPA), a known endocrine disruptor, interferes with the endocrine system, causing reproductive dysfunction. Recently, BPA has been found in waste water due to incomplete sewage purification, possibly threatening health through its ingestion via tap water. In this study, young male mice (6 - 7 weeks old) were administered water containing BPA (50 mg·kg^-1) for four weeks, while control mice consumed water without BPA. Serum, epididymal spermatozoa and testicular sections were assessed after sacrificing the mice on day 28. No significant differences were obtained between the groups in the body, testis and seminal vesicle weights. However, the epididymal sperm motility and count levels were significantly reduced in BPA-fed mice. Significantly higher hepatotoxicity levels were also observed in mice ingesting BPA as compared to the control mice. The level of serum testosterone was reduced, and testicular sections revealed incomplete and irregular spermatogenesis in BPA-ingested mice. The sperm proteasomal-proteolytic activity level has been implicated in sperm function and is measured in motile spermatozoa using fluorometric substrates. High ubiquitin C-terminal hydrolase activity levels were observed in the control mice without BPA. During a mating trial, a low pregnancy rate (71.4%) was observed in females mated with males who had consumed BPA (100% in the control mice). Overall, BPA adversely affected spermatogenesis and quality, as indicated by decreased sperm motility, concentration and serum testosterone levels, resulting in reduced fertility competence.

• Journal of Korean Medicine Rehabilitation
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• v.34 no.2
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• pp.1-14
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• 2024

Objectives The purpose of this study is to evaluate the fracture healing effect of extracts from Cnidium officinale and Angelica sinensis (CO/AS) in mice with femoral fracture. Methods C57BL/6 mice were randomly divided into normal, control (phospate-bufferd saline), positive control (tramadol), CO/AS extract 40 mg/kg and 80 mg/kg. By using Collier's method, all groups except normal group went through femoral fracture. Aspartate aminotransferase (AST), alanine transferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and creatinine were measured to evaluate the safety of CO/AS. Hematoxylin & eosin, Safranin O staining, x-ray, tensile and compressive force were conducted to assess the effect of CO/AS on fracture. Results The liver function test showed AST, ALT and LDH in CO/AS at 14th and 28th days were not significantly different compared with control group. The renal function test showed BUN in CO/AS at 14th days and BUN and creatinine in CO/AS at 28th days were significantly decreased compared with control group. The morphological & histological analysis and x-ray showed that CO/AS promoted cartilage and callus formation process compared with control group. The tensile and compressive forces test showed tensile in CO/AS 40 mg/kg and tensile & compressive forces in CO/AS 80 mg/kg were significantly increased compared with control group. Conclusions CO/AS extract showed the possibility that it promotes early fracture union and increases bone tensile and compressive strength, while does not have hepatotoxicity. In conclusion, CO/AS has a potential to promote healing of bone fracture and this study warranted the clinical usage of CO/AS at bone fracture.

• Journal of The Korean Society of Clinical Toxicology
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• v.21 no.2
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• pp.128-134
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• 2023

Purpose: The Prescott nomogram has been utilized to forecast hepatotoxicity from acute acetaminophen poisoning. In developing countries, emergency medical centers lack the resources to report acetaminophen concentrations; thus, the commencement and cessation of treatment are based on the reported dose. This study investigated risk factors that can predict acetaminophen detection after 15 hours for safe treatment termination. Methods: Data were collected from an urban emergency medical center from 2010 to 2020. The study included patients ≥14 years of age with acute acetaminophen poisoning within 15 hours. The correlation between risk factors and detection of acetaminophen 15 hours after ingestion was evaluated using logistic regression, and the area under the curve (AUC) was calculated. Results: In total, 181 patients were included in the primary analysis; the median dose was 150.9 mg/kg and 35 patients (19.3%) had acetaminophen detected 15 hours after ingestion. The dose per weight and the time to visit were significant predictors for acetaminophen detection after 15 hours (odds ratio, 1.020 and 1.030, respectively). The AUCs were 0.628 for a 135 mg/kg cut-off value and 0.658 for a cut-off 450 minutes, and that of the combined model was 0.714 (sensitivity: 45.7%, specificity: 91.8%). Conclusion: Where acetaminophen concentrations are not reported during treatment following the UK guidelines, it is safe to start N-acetylcysteine immediately for patients who are ≥14 years old, visit within 15 hours after acute poisoning, and report having ingested ≥135 mg/kg. Additional N-acetylcysteine doses should be considered for patients visiting after 8 hours.

• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.45-53
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• 1980

Lipid peroxidation in vitro has been identified as a basic deteriorative reaction in cellular mechanism of aging processes, such as air pollution oxidant damage to cell and to the lung, chlorinated hydrocarbon hepatotoxicity. Many experimental evidences were reported by several investigators that lipid peroxidation could be one of the principle causes for the hepatotoxicity produced by $CCl_4$. It is now reasonably established that $CCl_4$ is activated to a free radical in vivo, that lipid peroxidation occurs very quickly in microsomes prepared from damaged livers, that the peroxidation is associated with loss of enzyme activity of microsomes, and that various antioxidants can protect animals against the hepatotoxic effect of $CCl_4$. Recent studies have drawn attention to some other feature of microsomal lipid peroxidation. Incubation of liver microsomes in the presence of NADPH has led to a loss of cytochrome $P_{450}$. However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome $P_{450}$. Decrease of cytochrome $P_{450}$ in microsomes under in vitro incubation can be enhanced by $CCl_4 and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde. The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with $CCl_4$. Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. $CCl_$ and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from liver of animals and TBA value as well as the activity of drug metabolizing enzyme were measured in the microsomal fractions. The results are summerized as following. 1) The secobarbital induced sleeping time of $CCl_4$ treated rat was about 2 times longer than that of the control group. However, the pretreatment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_4$ treatment. Furthermore TBA value was significantly increased in $CCl_4$ treated rat in comparison to control group tut the increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. On the other hand, the activity of hepatic drug metabolizing enzyme was decreased in $CCl_4$ group, however, the pretreatment with riboflavin tetrabutylate also prevented the decrease of the enzyme activity caused by $CCl_4$. 2) The effect of riboflavin tetrabutylate on TBA value and the activity of drug metabolizing enzyme in vitro was similar to in vivo results. Incubation of liver microsome from rat in the presence of $CCl_4$, $Fe^{++}$, or ascorbic acid has led to the marked increase of TBA value, however, the addition of riboflavin tetrabutylate in incubation mixture prevented significantly the increase of TBA value, suggesting the inhibition of lipid peroxidation. In accordance with TBA value, the activity of drug metabolizing enzyme was inhibited in the presence of $CCl_4$, $Fe^{++}$, ascorbic acid but the addition of riboflavin tetrabutylate protected the loss of the enzyme activity in microsome under in vitro incubation.

• Korean Journal of Environmental Agriculture
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• v.33 no.4
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• pp.395-402
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• 2014

BACKGROUND: Azadirachta indica Extract(AIE) containing azadirachtin as active ingredient have been used worldwide as environment-friendly organic material having pest control properties. However, the extracts prepared with different solvent and from different plant site is very diverse and have different toxicity. METHODS AND RESULTS: In this study, the four week repeated oral dose toxicity test of aqueous AIE in Sprague-Dawley rats was carried out to investigate the toxic effect of liver, main toxicity target organ of AIE. The male and female rats were divided into 4 groups, respectively; control(0 g/Kg bw), low-dose group(0.5 g/Kg bw), middle-dose(1.0 g/Kg bw) and high-dose group(2.0 g/Kg bw). As a results, relative liver weight increased with dose-dependent of AIE(p<0.05). Serum LDH in all AIE-treated groups were significantly lower than the control in male rats(p<0.05). However, serum GOT and GPT were significantly increased in all male AIE-treated groups in male rats(p<0.05) and, in particular, increase of serum GPT in dose-dependent manner raise the possibility of liver damage. Even through serum GLU was increased significantly in high-dose group in male rats compared to control, there were no significant differences of urinary GLU among all groups(p<0.05). In addition, histopathological examination of the liver did not reveal any lesions in all AIE-treated groups. CONCLUSION: In conclusion, 4 weeks of the repeated oral administration of AIE 2.0 g/Kg to rats has resulted no toxic response in liver. Therefore, AIE was no indicated to have any toxic effect in the SD rats, when it was orally administrated below the dosage 2.0 g/Kg/day for 4weeks.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1422-1430
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• 2015

This study was conducted to determine the effect of fermented water extracts from Ligularia fischeri (LAF) on reduction of hepatotoxicity induced by D-galactosamine (D-GalN) in rats. In this experiment, male Sprague-Dawley rats were used as experimental animals, which were divided into eight groups: normal group, D-GalN-treated group (control), D-GalN and non-fermented water extracts from Ligularia fischeri (LA)-treated groups [100, 200, and 400 mg/kg BW (body weight)], and D-GalN and LAF-treated groups (100, 200, and 400 mg/kg BW). ${\gamma}$-Glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities in serum of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05). The high density lipoprotein-cholesterol levels of the D-GalN and LAF-treated groups increased significantly compared to those of the control group (P<0.05). The low density lipoprotein-cholesterol and triglyceride levels of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05). The atherogenic index values of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05), and their high density lipoprotein cholesterol by total cholesterol ratio increased significantly in these groups (P<0.05). Superoxide dismutase activity of liver tissues were enhanced significantly (P<0.05) in the D-GalN and LAF-treated groups compared to that of the control group (P<0.05), whereas their malondialdehyde content decreased significantly in these groups (P<0.05). The histopathological observations revealed apoptotic cells and mild portal inflammation in liver tissues of the D-GalN and LAF-treated groups. Taken together, these results demonstrate that LAF may improve plasma lipid profile and alleviate hepatic damage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1431-1438
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• 2015

This study was conducted to determine the effects of fermented water extracts from Ligularia fischeri (LAF) on reduction of hepatotoxicity induced by ethanol in rats. Ethanol-treated Sprague-Dawley rats were divided into the following eight groups: ethanol-treated group (control), ethanol and ursodeoxycholic acid-treated group (positive control), ethanol and non-fermented water extracts from Ligularia fischeri (LA)-treated groups [100, 200, and 400 mg/kg BW (body weight)], ethanol and LAF-treated groups (100, 200, and 400 mg/kg BW). ${\gamma}$-Glutamyl transferase activities of the ethanol+LA-treated (100, 200, and 400 mg/kg BW) groups and ethanol+LAF-treated (400 mg/kg BW) group decreased significantly compared to those in the control group (P<0.05). Aspartate aminotransferase activities of the ethanol+LAF-treated (100, 200, and 400 mg/kg BW) groups and ethanol+LA-treated (200 and 400 mg/kg BW) groups decreased significantly compared to those in the control group (P<0.05). Alanine aminotransferase and lactate dehydrogenase activities of all groups significantly decreased compared to those in the control group (P<0.05). The total cholesterol, low density lipoprotein-cholesterol, and triglyceride levels of all groups tended to decrease compared to those in the control group, but the differences were not significant. Superoxide dismutase activity of liver tissues was enhanced in the ethanol+LAF-treated (400 mg/kg BW) group (P<0.05). The contents of malondialdehyde in liver tissues decreased in the ethanol+LAF-treated groups (P<0.05). All treated groups showed well preserved lobular architectures with no evidence of steatosis or liver damage compared to the control group. As the results of this study, LAF may improve the plasma lipid profile and alleviate hepatic damage by ethanol.