• Journal of Nutrition and Health
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• 제30권7호
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• pp.751-769
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• 1997

This study was performed to investigate the effect of chitosan and NOCC from different sources and of different molecular weights on cadmium toxicity. Sprague-Dawley rats were blocked into 26 groups according to body weight, and were raised for 4 weeks. Cadmium chloride was given at the level of 0 or 400 ppm in diet. Various forms of chitosan and NOCC were given at the level of 0 or 4%(w/w) of diet. Cd toxicity was alleviated by various chitosan and NOCC supplements. However, the alleviating effects were different with fiber source(crab and shrimp), type(chitosan and NOCC), and molecular weight (low, medium, and high). Molecular weight had no significant effect. Compared with shrimp-source-fiber-fed groups, crab-source-fiber-fed groups showed lower Cd concentrations in blood and kidney, lower kidney metallothionein concentration, and lower liver and kidney MT-Cd contents. Compared with NOCC -fed groups, chitosan-fed groups showed lower intestine and liver Cd concentrations, lower liver and kidney MT concentrations and MT-Cd content, and higher fecal Cd excretion. Among cadmium-exposed group, low molecular weight shrimp chitosan group showed low Cd concentrations of liver and kidney, high fecal Cd excretions, and the lowest intestine and liver MT concentrations and liver MT-Cd content. In summary, a crab source fiber was more effective than shrimp source fiber, chitosan was more effective than NOCC, and the most effective one in alleviating Cd toxicity was low molecular weight shrimp chitosan.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.205-210
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• 2021

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

• Toxicological Research
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• 제12권1호
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• pp.29-34
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• 1996

1,2,4-trichlorobenzene (1,2,4-TCB) is used as a dye carrier, an intermediate in the syn[hesis of herbicides, aflame retardant, and for other purpose. After a single oral administration of 1,2,4-TCB (200 mg/kg, 400 mg/kg) in rats, toxic effects were studied by means of serum biochemical and hematological analysis, and liver calcium concentration. Administration of 1,2,4-TCB resulted in dose-dependent manner liver and kidney damage being suggested by increased serum alanine aminbtransferase (ALT) activities, liver calcium concentration and blood urea nitrogen (BUN). Pretreatment with DL-buthionine sulfoximine (BSO, 2 mmol/kg, i.p.) considerably decreased liver glatathione concentration, which was accompanied by markedly elevated serum ALT activites. It is well-known that toxicity of halogenated benzene such as bromobenzene, 1,4-dichlorobenzene is increased by pretreatment of phenobarbital, and protected by pretreatment of cytochrorn P450 inhibitor including metyrapone. However, there were no obvious alterations in toxicity of 1,2,4-TCB by pretreatment of phenobarbital or metyrapone. In comparison with control group, treatment groups exhibited significant changes in some parameters of hematological analysis but all hematological values remained within normal ranges.

• Toxicological Research
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• 제33권3호
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• pp.173-182
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• 2017

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.

• 약학회지
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• 제39권4호
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• pp.450-460
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• 1995

The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.

• 대한본초학회지
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• 제22권4호
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• pp.169-176
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• 2007

Objective : This study purposed to investigate the anti-oxidative effect of Lithospermi Radix (root of Lithospermum erythrorhizon S.) on liver cells isolated from oxidatvely stressed rat by AAPH. Method : We investigate effects of Lithospermi Radix(LR) and its fractions on normal liver cells' proliferation. And the amounts of SOD, GSH, catalase, NO, MDA production by liver cells isolated from the oxidatively stressed rat by AAPH also were measured after incubation with various fractions of LR extraction. Results : LR and its fracitons showed no toxicity on the normal liver cells from rat. LR and its fracitons increased the activity of SOD and reduced the amounts of NO and MDA in the liver cells from the oxidatively stressed rat. Conclusion : Lithospermi Radix could be supposed to have antioxidant effect on liver cells with no toxicity.

• Toxicological Research
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• 제33권1호
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• pp.15-23
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• 2017

Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

• 한국수산과학회지
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• 제40권5호
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• pp.269-275
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• 2007

The toxicity of two species of puffer fish, Takifugu pardalis and T. niphobles, collected from the coastal regions of Korea was determined using a mouse bioassay. In T. pardalis collected at Tongyeong, the proportion of toxic specimens containing ${\geq}10MU/g$ exceeded 90% for the skin, fins, liver, intestine, ovary, and gallbladder, 11.1% for the testis, and 6.9% for the muscle. In each of the organs, the highest toxin levels were several tens (14-39) of mouse units (MU) per gram in the muscle, testis, and eyeball, but thousands (1,444-5,755) of MU per gram in the skin, liver, intestine, ovary, and gallbladder. The organs of T. pardalis exhibited remarkable variation in toxicity. In T. niphobles, the proportion of toxic specimens exceeded 90% for the ovary and skin, 60-80% for the fins, liver, intestine, and gallbladder, and 4.5% for the muscle; no toxicity was detected in the testis or eyeball using the mouse bioassay. The highest toxin levels were thousands (2,291-7,777) of MU per gram in the liver, intestine, ovary, and gallbladder, hundreds(146-328) of MU per gram in the skin and fins, and 18 MU/g in the muscle. Takifugu niphobles toxicity also exhibited remarkable regional variation. The toxicity in the edible muscle of T. pardalis and T. niphobles was at acceptable levels for human consumption, while the toxicity of the skin of both species of puffer fish was very high, so that care must be taken when used for human consumption.

• 한국환경보건학회지
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• 제48권2호
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• pp.106-115
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• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.

• 한국어병학회지
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• 제36권2호
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• pp.415-422
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• 2023

In veterinary medicine for mammals, studies are being conducted to confirm the effects of antioxidants using pathological toxicity model studies, and are also used to confirm the effect of mitigating liver or kidney toxicity of specific substances. It was considered necessary to study such a toxicity model for domestic farmed fish, so thioacetamide (TAA), a toxic substance that causes tissue damage by mitochondrial dysfunction, was injected into rainbow trout (Oncorhynchus mykiss), a major farmed freshwater fish species in Korea. The experiment was conducted with 40 rainbow trout (Oncorhynchus mykiss) weighting 53 ± 0.6 g divided into two groups. Thioacetamide(TAA) 300mg/kg of body weight was intraperitoneally injected into rainbow trout and samples were taken 1, 3, 5, 7 days after peritoneal injection. As a result, in serum biochemical analysis, AST levels related to liver function decreased 3 and 5 days after intraperitoneal injection and increased after 7 days, and ALT levels also increased after 7 days. In addition, creatinine related to renal malfunction increased 3 and 5 days after TAA injection. In histopathological analysis, pericholangitis and local lymphocyte infiltration were observed in the liver from 1 day after intraperitoneal injection of TAA, and hepatic parenchymal cell necrosis was also observed from 3 days after intraperitoneal injection. Hyaline droplet in renal tubular epithelial cell was observed from 1 day after TAA injection, and acute tubular damage such as tubular epithelial cell necrosis appeared from 3 days after TAA injection. Accordingly, it is thought that it will be able to contribute to studies that require a toxicity model.