• Natural Product Sciences
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• v.20 no.4
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• pp.262-268
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• 2014

Rutaecarpine is one of the major alkaloids present in the fruits of Evodia rutaecarpa. In this study, rutaecarpine was evaluated, both in vitro and in vivo, for its hepatoprotective properties against thioacetamide (TAA)-induced hepatic fibrosis. The results showed that rutaecarpine inhibited TAA-induced cytotoxicity, reduced the expression of the fibrogenic cytokine transforming growth factor ${\beta}1$ ($TGF-{\beta}1$), and induced the expression of bcl-2. To evaluate its in vivo effects, animal models with TAA-induced hepatic fibrosis were utilized. Levels of liver tissue injury-associated enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were monitored. $TGF-{\beta}1$ and the ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) were measured as markers of the protective effects on hepatic fibrosis. The AST and ALT levels in blood were greatly enhanced by TAA and completely blunted by rutaecarpine. Rutaecarpine led to the down-regulation of $TGF-{\beta}$ and Bax mRNA expression, as well as the up-regulation of Bcl-2 and $Bcl-X_L$ mRNA levels. In conclusion, rutaecarpine inhibited TAA-induced hepatic fibrosis and apoptosis by inducing the expression of Bcl-2 while blocking $TGF-{\beta}1$ in our TAA-intoxicated model.

• Korean Journal of Veterinary Service
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• v.36 no.4
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• pp.233-242
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• 2013

The genus Taraxacum, known by the common name Dandelion, is a medicinal herb in the family Asteraceae. It has been traditionally used as a folk medicine for the treatment or prevention of various diseases due to its anti-inflammatory and anti-oxidative properties. In this study, we attempted to evaluate protective effects of Dandelion related with anti-oxidative activity to Thioacetamide (TAA)-induced liver damage. 36 rats were randomly assigned to six experimental groups : Control, Dandelion water extract (DWE), TAA, TAA&DWE 300, TAA&DWE 600, TAA&DWE 1,200 groups. Rats in DWE and TAA&DWE groups were pretreated with DWE (300, 600 or 1,200 mg/kg BW) by gavage for 7 days. All rats were treated intraperitoneally with TAA (200 mg/kg BW) or normal saline at 12 hours after last oral administration and sacrificed at 12 hours after last treatment. Levels of WBC and Neutrophil count were significantly decresed in TAA&DWE 1,200 group compared with that in TAA group (P<0.05). In TAA&DWE 600 and TAA&DWE 1,200 groups, serum AST, ALT, GGT levels were lower than TAA group (P<0.05). The serum TG level was significantly elevated in TAA&DWE groups compared with those in TAA group. Liver tissues from TAA group showed extensive histopathological changes, characterized by moderate or severe hepatocytes degeneration, inflammatory cell infiltration, and congestion. In the TAA&DWE group, The severity of histopathological lesions were decreased compared to those in the TAA group. The MDA concentration was significantly decreased and GSH content was significantly increased in the TAA&DWE 1,200 group compared to those in the TAA group. GR, CAT and GST activities in the TAA&DWE 1,200 group were significantly increased compared to those in the TAA group.

• Korean Journal of Acupuncture
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• v.36 no.4
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• pp.221-229
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• 2019

Objectives : This study investigated the hepatoprotective effect of herbal mixture including Lycii fructus (HML) in thioacetamide (TAA)-induced hepatotoxicity in mice. Methods : To confirm the liver protective effect, induced by TAA for 3 days injection at 100 mg/kg mice, HML were treated for 8 weeks at 300 mg/kg/day, 1000 mg/kg/day. Positive control was treated silymarin 50 mg/kg/day after TAA injection. The changes of mortality rate, clinical signs, organ weight, relative liver, blood chemistry and histopathological findings were analyzed after experiment. Results : Body weight gain was observed in all groups, but TAA treated group at 4th week and all treated groups decreased weight compared to the untreated group. As a result of organ weight measurement, organ weight gain due to hepatic injury was observed statistically significantly in TAA-treated group and TAA+Silymarin treated group, and the herbal mixture-treated group showed a tendency to decrease compared to the TAA treated group. Blood biochemistry showed that total cholesterol and very low density lipoprotein cholesterol decreased statistically in TAA+low-dose and high dose herbal mixture treated group compared to the TAA-treated group. Histopathological examination showed that liver abnormalities were not observed in untreated group, liver fibrosis was observed in liver injury with TAA treated and herbal mixture treated group. And, TAA+high dose herbal mixture group showed relaxation tendency on liver calcification compared to the TAA treated group. Conclusions : According to the above results, HML provided hepatoprotective effects on the hepatic injury by reduction of inflammatory responses.

• Journal of fish pathology
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• v.36 no.2
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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.

• Korean Journal of Veterinary Service
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• v.40 no.2
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• pp.107-117
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• 2017

This study was conducted to investigate of hepatoprotective effect of dandelion water extract (DWE) according to repeated administration of thioacetamide (TAA) induced hepatotoxicity in Spraque-Dawley rats. Thirty rats were randomly assigned to 5 groups; normal control, DWE-control, TAA-control (TAA injection during the feeding of normal diet), TAA&DWE600 (TAA repeated injection during the feeding of DWE 600 mg/kg BW), TAA&DWE1200 (TAA repeated injection during the feeding of DWE 1,200 mg/kg BW). Rats in DWE-control and TAA&DWE groups were treated with DWE (600 or 1,200 mg/kg BW daily) by gavage for 20 days (twice a day). All the rats in the TAA-control and TAA&DWE groups were repeated injection of TAA (100 mg/kg BW) into the abdominal cavity 3 days interval and 12 hrs later, all rats were sacrificed. At the same time, normal control and DWE-control groups were injected normal saline. In TAA&DWE groups, serum alanine and aspartate aminotransferase (ALT, AST) were significantly decreased and triglyceride (TG) synthesis was significantly increased compared to TAA group. As well as total billilubin and GGT were slightly decreased by the treatment of DWE. Lipid peroxidation (MDA) concentration was significantly decreased and hepatic GSH content was slightly or significantly increased in the TAA&DWE groups compared to TAA group. Hepatic anti-oxidative enzyme activities, such as GSH, GST, SOD and catalase were slightly or significantly elevated by the treatment of DWE. According to these results, When dandelion extract was long term supplied, it could be used as a potential protective material for a longer time liver damage by repeated adminstration of the TAA.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.643-655
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• 2022

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

• Journal of Nutrition and Health
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• v.54 no.4
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• pp.412-421
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• 2021

Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAA-induced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22^phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidant-related factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22^phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.

• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1223-1236
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• 2021

Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms. Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting. Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen I. Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.

• Journal of the Korean Chemical Society
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• v.25 no.4
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• pp.207-213
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• 1981

Conformations of thioacetamide (TAA) and its protonated form were determined using the CNDO/2 method, and the intermolecular interaction energies between the protonated TAA and water were calculated. It was found that: (1) protonation occurs preferentially on the N rather than on the S atom, (2) the stabilization energy of intermolecular perturbation between the protonated TAA and water was also large for the N-protonated TAA. This causes preferential CS bond cleavage due to large antibonding nature of the CS bond in the LUMO, and leads to an orbital controlled reaction.

• Journal of Nutrition and Health
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• v.54 no.2
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• pp.224-237
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• 2021

Purpose: Paeonia Radix Alba is a traditional herbal medicine used to treat the liver and the spleen. Many studies have reported that Paeonia Radix Alba extract (PR) affects liver injury, but there has been no study on liver injuries induced by thioacetamide (TAA). Therefore, we aimed at evaluating the effect of PR on a TAA-induced acute liver injury (ALI) model. Methods: The antioxidant activity of PR was assayed by the content of total polyphenol, total flavonoid, 1,1-diphenyl-2'-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical scavenging activities in vitro test. ALI was induced via-intraperitoneal injection of TAA (200 mg/kg body weight) for three consecutive days. Also, silymarin (100 mg/kg body weight) and PR (100 or 200 mg/kg body weight) were administered at 1 hours 30 minutes prior to TAA treatment. The levels of ammonia, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were analyzed using an assay kit. The expressions of antioxidant proteins including Nrf2, Keap1, HO-1, SOD, catalase, and GPx-1/2 and oxidative stress-related proteins including NOX2, p47^phox, and p22^phox were evaluated by the western blot analysis. Results: PR showed excellent antioxidant activity in vitro. TAA administration increased the levels of ammonia, GOT, and GPT in the ALI control group compared to the normal group, whereas it was significantly reduced by PR pretreatment. Moreover, NADPH oxidase protein expressions were upregulated after TAA treatment, while the elevated expressions were inhibited by PR pretreatment. The expressions of antioxidant protein were downregulated in the ALI control group, whereas Nrf2 activation in the PR group was accompanied by increased levels of antioxidant enzymes. Conclusion: PR administration increased the antioxidant enzymes via activation of the Keap1/Nrf2 pathway and inhibited the protein levels of NADPH oxidase factors. Taken together, these results showed that PR treatment may be considered to ameliorate acute liver injury induced by TAA.