[Show abstract][Hide abstract] ABSTRACT: Three chemotoxins including dimethylnitrosamine (DMN), carbon tetrachloride (CCl4), and thioacetamide (TAA) are commonly used in hepatofibrotic models. We aimed to draw characteristics of histopathology and pro-fibrogenic cytokines including TGF-β, PDGF and CTGF among three models. Rats were divided into six groups and intra-peritoneally injected with DMN (10 mg/kg, for three weeks, three consecutive days weekly), CCl4 (1.6 g/kg, for 10 weeks, twice weekly), TAA (200 mg/kg, for 12 weeks, twice weekly) or their corresponded treatment for each control group. The liver weights were decreased in DMN model, but not other models. Ascites were occurred as 3-, 2-, and 7-rats in DMN, CCl4, and TAA model, respectively. The lipid peroxidation was highest in CCl4 model, serum levels of liver enzymes were increased as similar severity. The hepatofibrotic alterations were remarkable in DMN and TAA model, but not CCl4 as evidenced by the Masson trichrome staining and hydroxyproline. The immunohistochemistry for α-SAM showed that the DMN model was most severely enhanced than other models. On the other hand, hepatic tissue levels of pro-fibrogenic cytokines including TGF-β, PDGF, and CTGF were generally increased in three models, but totally different among models or measurement resources. Especially, serum levels of three cytokines were remarkably increased by CCl4 injection and CTGF levels in both hepatic tissue and serum were highest in CCl4 group. Our results firstly demonstrated comparative study for features of morphological finding and pro-fibrogenic cytokines in serum and hepatic protein levels among three models. Above results would be a helpful reference for hepatofibrotic studies.
Full-text · Article · Jun 2015 · Drug and Chemical Toxicology
[Show abstract][Hide abstract] ABSTRACT: ETHNOPHARMACOLOGIC RELEVANCE: Artemisia capillaris, also called "InJin" in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine. AIMS: The purpose of this study is to evaluate the hepatoprotective effect of A. capillaris (aqueous extract, WAC) on alcoholic liver injury. MATERIALS AND METHODS: Liver injury was induced by oral administration of 30% alcohol (10mL/kg, twice per day) plus pyrazole (PRZ, 30mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days. The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level respectively. RESULTS: Alcohol-PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol-PRZ treatment, but notably attenuated by WAC administration. Moreover, the alcohol-PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Alcohol-PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in hepatic tissues. However they were significantly normalized by WAC administration (p<0.05 or 0.01). In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH). CONCLUSIONS: These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines.
Full-text · Article · Mar 2013 · Journal of ethnopharmacology
[Show abstract][Hide abstract] ABSTRACT: Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50mg/kg) or urosodeoxycholic acid (UDCA, 25mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.
Full-text · Article · Jan 2013 · Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie
[Show abstract][Hide abstract] ABSTRACT: Cholestatic liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins, is associated with bile acid-induced oxidative stress and lipid peroxidation. We evaluated the therapeutic or protective effect of an aqueous extract of Artemisia iwayomogi Kitamura (WAI) in a rat bile duct ligation (BDL)-induced hepatic fibrogenesis model. After BDL, rats were treated once daily with 25 or 50mg/kg of WAI for 2weeks. The serum bilirubin, aspartate transaminase, alanine transaminase, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group. WAI administration significantly reduced these markers and restored BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAI treatment, and these changes were paralleled by significantly suppressed gene and protein expression of fibrogenic factors, including hepatic alphasmooth muscle actin, platelet-derived growth factor, and transforming growth factor β. Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL.
Full-text · Article · Jul 2012 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
[Show abstract][Hide abstract] ABSTRACT: We examined how chemotherapy-induced myelotoxicity and the associated leukopaenia affect cancer metastasis in an animal model. Myelotoxicity was induced by a single injection of 5-fluorouracil (5-FU) or Cisplatin, administered to 7-week-old BALB/c mice. CT-26 murine colon carcinoma cells were injected into the lateral tail vein on days 0, 1, 3, 5, and 7 after anticancer drug injection. On day 14 after cancer cell injection, the number of pulmonary colonies was measured in a double-blind setting. Compared with Cisplatin, 5-FU induced severe leukopaenia and bone marrow suppression, while on day 5, both drugs induced severe myelotoxicity. The number of pulmonary colonies did not correlate with the severity of leukopaenia, regardless of the type or time of drug injection, except in the group pretreated with Cisplatin (3 days prior to cancer cell injection). Our results suggest that chemotherapy-induced myelotoxicity does not increase the incidence of cancer metastasis in this animal model.
No preview · Article · Jul 2011 · Human & Experimental Toxicology
[Show abstract][Hide abstract] ABSTRACT: We investigated the antioxidant effects of Panax ginseng C.A. Meyer on healthy volunteers. In a double-blind randomized controlled design, 82 participants (21 men and 61 women) who were considered healthy by both objective and subjective health standard were divided into three groups, the control group and the groups received P. ginseng extract (1 or 2g/day) for 4 weeks. Serum level of reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC), the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and peroxidase (GSH-Px), and total glutathione content were determined before and after the trial. Administration of P. ginseng led to significant decreases in the levels of serum ROS and MDA. Notably, the total glutathione content and GSH-Rd activity considerably improved in the groups that received 2g of P. ginseng. No significant alterations were observed in TAC, catalase, SOD, and GSH-Px activities. In conclusion, our findings indicate that P. ginseng was shown to have antioxidant property. It enhanced the antioxidant defense mechanism in healthy populations and the results may reinforce the use of P. ginseng as a potential antioxidant supplement.
No preview · Article · Jun 2011 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
[Show abstract][Hide abstract] ABSTRACT: In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100 mg/kg) or after (12.5, 25, and 50 mg/kg) a single intraperitoneal injection of cisplatin (7 and 6 mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24 h for 120 h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50 mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72 h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120 h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50 mg/kg) at 24 h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72 h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5 mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.
No preview · Article · Oct 2010 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
[Show abstract][Hide abstract] ABSTRACT: CGX is a potential hepatoprotective herbal medicine used to treat various chronic liver disorders. The purpose of the study was to evaluate the pharmaceutical safety of CGX via a systemic 13-week repeated dose toxicity test in beagle dogs. Male and female beagle dogs were divided into four groups and two animals each from the control and high-dose group (400 mg/kg) were allocated into recovery groups. The dogs were administered with CGX (0, 100, 200, 400 mg/kg) for 13 weeks. During the experimental period, the dogs were observed for signs of gross toxicity and for behavioral changes; body weight and food consumption were measured. An ophthalmologic examination and urinalysis were performed at 0 and 13th week and blood biochemistry and hematological parameters analyses were performed at 0, 6th, and 13th week. A histopathological examination was also performed at the end of the experiment. There were no CGX-induced abnormalities in clinical signs, organ weights, food consumption, hematological, urine, and blood biochemical parameters, or histopathological findings in any of the groups during or after the 13 weeks. We demonstrated the safety of CGX for 13-week repeated dose and considered that it is safe for chronic clinical use.
No preview · Article · Feb 2010 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association