• YAKHAK HOEJI
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• v.44 no.6
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• pp.552-557
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• 2000

In order to investigate the effects of Yukmijihwang-Tang on the hepatic microsomal function of Cd-poisoned rats, 3 mg/kg of cadmium (Cd) and 500 mg/kg of Yukmijihwang-Tang extract (YJT), a herbal hepatoprotective medicine, were administered concurrently to rats for 4 weeks. The levels of protein, aniline hydroxylase (AH) and malondialdehyde (MDA) were increased in Cd-treated group. This increase was suppressed by treatment or YJT. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose-6-phosphatase (G-6-P) and ${\delta}-aminolevulinic$ acid dehydratase (ALAD) of Cd-treated group were decreased. This decrease was inhibited by treatment of YJT. Treatment with YJT significantly protects cadmium-induced hepatotoxicity.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.37-44
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• 2013

Korean red ginseng is known to regulate the immune system and help the body struggle infection and disease. Cadmium is widely distributed in the environment due to its use in industry. Exposure to cadmium is problematic causing organ dysfunction. This study was conducted to evaluate the protective effect of Korean red ginseng extract (RGE) against cadmium-induced hepatotoxicity in rats. In experiments, animals were orally administrated with RGE (25, 50 mg/kg) for 7 d and then intravenously injected with cadmium ($CdCl_2$, 4 mg/kg) to induce acute hepatotoxicity. Cadmium caused the elevated levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in serum. In contrast, pretreatment with RGE significantly reduced those serum indexes related with liver damage. In histopathological analysis, RGE decreased the centrilobular necrosis around central veins and the peripheral hemorrhage around portal triads. Moreover, RGE restored the deficit in hepatic glutathione level resulting from cadmium treatment. RGE also inhibited the increase in the expression of Bad, a representative apoptosis marker protein, induced by cadmium treatment. Collectively, these results demonstrate that RGE can reduce the cadmium-induced hepatic toxicity, partly via anti-oxidative and anti-apoptotic process.

• Applied Microscopy
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• v.32 no.4
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• pp.361-376
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• 2002

This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the other group was injected with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, cadmium concentration in liver tissues and metallothionein (MT) concentration were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. Cadmium concentration in liver tissues was drastically lower in groups Cd+Chi than in group Cd. MT concentration in liver tissues was lower in group Cd than in groups Cd+Chi. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi, mitochondria with high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

• Applied Microscopy
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• v.32 no.3
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• pp.231-246
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• 2002

This study was carried out to investigate the effect of squalene (SQ) on the mouse hepatotoxicity induced by cadmium. ICR male mouse weighting about 30 gm were injected $CdCl_2$ (5.0 mg/kg) and SQ (180 mg/kg) into intraperitoneal. At the 1, 2, 3, 4, 5, 6, 7 days, livers were treated with superoxide dismutase (SOD) activity and transmission electron microscopical method and then observed with electron microscope. The results obtained were summarized as follows: SOD activity in the liver, Group A was higher than in normal. Group B was lower than in Group A. In the histological observation, nucleus of Group A showed irregular shape. Inner cavity of mitochondria swellen and development of cristae weakened. Swelling of Lamellae of rough endoplasmic reticulum (RER) showed. Nucleus of group B showed normal shape. Typical lamellae of RER were observed. These results described above treatment of SQ decreased the hepatotoxicity of the $CdCl_2$ and SOD activity in the mouse liver, and then it suggests SQ may be effective for the recovery of hepatic cell.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Environmental Health Sciences
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• v.20 no.2
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• pp.64-72
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• 1994

Tolerance to toxic effects of cadmium (Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 108 rats, were studied and each group was divided into three subgroups (1, 2, 3), 12 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl$_2$ (0.5 mg/kg, B), and ZnCl$_2$ (13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with CdCIa (3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggests that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretteatmerit, served to induced the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1003-1011
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• 2009

This study was carried out to know the effects of Kwanjulbang-6(GJB-6) on the inhibition of arthritis. GJB-6 was orally administered to mouse with arthritis induced by collagen II . Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node and paw joint, rheumatoid factor in serum were measured in vivo. The incidence of arthritis was significantly decreased. Total cell number of draining lymph node was significantly increased compared with control. Total cell number of paw joint was significantly decreased compared with control. The absolute number of $CD19^+$, $CD8^+$, $CD3^+/CD69^+$, $CD3^+/CD49b^+$, $CD4^+/CD44^+$, $CD3^+$, $CD4^+$, $CD4^+/CD25^+$ and $CD3^+/CD8^+$ cells in draining lymph node were significantly increased compared with control. The absolute number of $CD3^+$, $CD4^+$, $CD4^+/CD25^+$ and $CD11b^+/Gr-1^+$ cells in paw joint were significantly decreased compared with control. The absolute number of $B220^+/CD23^+$ and $MHCII^+/CD11c^+$ cell in draining lymph node were significantly decreased compared with control. The levels of IgG was decreased and The levels of IgM was significantly decreased compared with control. Anti-collagen II in serum was significantly decreased compared with control. With the hematoxylin and eosin stain, the cartilage destruction and synovial cell proliferation were decreased compared with control. With the Masson's trichrome stain, the expression of collagen fibers was decreased compared with control. Results showed that GJB-6 had immunomodulatory effects. So we expect that GJB-6 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease.

• Journal of Environmental Health Sciences
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• v.21 no.3
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• pp.1-15
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• 1995

Tolerance to toxic effects of cadmium(Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats(A, B, C), each consisting of 52 rats, were studied and each group was divided into three subgroups(1,2,3), 28 rats for each subgroup. Rats were subcutaneously pretreated with saline(A), $CdCl_2$(0.5 mg/kg, B), and $ZnCl_2$(13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with $CdCl_2$(3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after 1,3,5,6 days of pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target-organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggest that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretreatment, served to induce the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

• Applied Microscopy
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• v.33 no.1
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• pp.59-78
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• 2003

This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The first group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the second one with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). The third one which had already been injeted with chitosanoligosaccharide (0.5% Solution) aweek before (group Ch7+Cd) was used. In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, enzyme activity in serum, glutathione peroxidase (GSHPx) activity and glutathione reductase (GR) activity were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. As the result of enzyme activity in serum, the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in chitosanoligosaccharide-injected groups Cd+Chi and Chi7+Cd was lower than in group Cd. GSH-Px activity was sharply increased in groups Cd+Chi and Chi7+Cd compared to group Cd. GR activity was conspicuously decreased in groups Cd+Chi and Chi7+Cd compared to group Cd. As the result of light microscopic observation, liver cell necrosis caused by cadmium poisoning was obseved in liver cells. The finding of group Cd+Chi and Chi7+Cd was similar total on of normal groups. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi and Chi7+Cd, mitochondria wiht high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.147-169
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• 2007

To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.