• Journal of the Korean Society of Food Science and Nutrition
• /
• v.22 no.6
• /
• pp.678-684
• /
• 1993

To evaluate the role of xanthine oxidase in liver damage by CCl4, a group of rats were fed tungstate for a month, which suppressed the activities of xanthine oxidase in serum and liver. Control group of rats were fed standard diet without tungstate. Liver damage was induced both in tungstate fed and control groups by two intraperitoneal injections of CCl4 at the level of 0.1ml/100g body weight at intervals of 24 hours. Increases in the levels of serum alanine aminotransferase by CCl4 were significantly smaller in tungstate fed rats than in control rats. Concomitantly, histopathologic changes were less in tungstate fed rats than in control ones. In rats either treated with CCl4 or not, hepatic type O xanthine oxidase activities were remarkably reduced by tungstate feeding. Hepatic aniline hydroxylase activities were higher in rats fed tungstate than control rats when animals were not treated with CCl4, but the enzyme activities were lower in tungstate fed rats than control when they were treated with CCl4. Neither tungstate feeding nor CCl4 treatment caused any significant changes in hepatic glutathione contents, and activities of hepatic glutathione S-transferase, glutathione peroxidase and superoxide dismutase. It is concluded xanthine oxidase reaction augment CCl4 induced liver damage via oxygen free radical system.

• The Korean Journal of Physiology and Pharmacology
• /
• v.16 no.6
• /
• pp.447-453
• /
• 2012

TLR6 forms a heterodimer with TLR2 and TLR4. While proinflammatory roles of TLR2 and TLR4 are well documented, the role of TLR6 in inflammation is poorly understood. In order to understand mechanisms of action of TLR6 in inflammatory responses, we investigated the effects of FSL-1, the TLR6 ligand, on expression of chemokine CCL2 and cytokine IL-$1{\beta}$ and determined cellular factors involved in FSL-1-mediated expression of CCL2 and IL-$1{\beta}$ in mononuclear cells. Exposure of human monocytic leukemia THP-1 cells to FSL-1 resulted not only in enhanced secretion of CCL2 and IL-$1{\beta}$, but also profound induction of their gene transcripts. Expression of CCL2 was abrogated by treatment with OxPAPC, a TLR-2/4 inhibitor, while treatment with OxPAPC resulted in partially inhibited expression of IL-$1{\beta}$. Treatment with FSL-1 resulted in enhanced phosphorylation of Akt and mitogen-activated protein kinases and activation of protein kinase C. Treatment with pharmacological inhibitors, including SB202190, SP6001250, U0126, Akt inhibitor IV, LY294002, GF109203X, and RO318220 resulted in significantly attenuated FSL-1-mediated upregulation of CCL2 and IL-$1{\beta}$. Our results indicate that activation of TLR6 will trigger inflammatory responses by upregulating expression of CCL2 and IL-$1{\beta}$ via TLR-2/4, protein kinase C, PI3K-Akt, and mitogen-activated protein kinases.

• Korean Journal of Clinical Laboratory Science
• /
• v.44 no.4
• /
• pp.229-238
• /
• 2012

Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

• Journal of Radiation Industry
• /
• v.7 no.1
• /
• pp.81-85
• /
• 2013

This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

• Advances in Traditional Medicine
• /
• v.4 no.1
• /
• pp.28-36
• /
• 2004

The purpose of this study was to investigate the pharmacological effects of low-esterified pectin on carbon tetrachloride $(CCL_4)-induced$ hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily $CCL_4$ through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of pectin for 21 days. At the end of experiment rats were killed within 24 hours. The increased bilirubin level, enhanced alanine aminotransferase and aspartate aminotransferase activity in plasma induced by $CCL_4$ were partly normalized by pectin administration in a dose-dependent manner. The pectin treatment also resulted in significant recovery of $CCL_4-induced$ decrease of the liver glycogen content. In addition, pectin significantly improved $CCL_4-induced$ alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered $CCL_4$. In the second experiment the animals were given daily 10, 50 or 250 mg/ kg b.w. of pectin for 21 days before a 7-day administration of $CCL_4$. Rats were killed 24 hours after the end of experiment. Pretreatment with pectin before $CCL_4$ administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of pectin prevented elevation of malondialdehyde and conjugated diene levels in liver and plasma as well as a reduction of glutathione content in liver of rats given $CCL_4$. These results suggest that low-esterified pectin exert healing and preventive effects on $CCL_4-induced$ hepatotoxicity in rats.

• Environmental Analysis Health and Toxicology
• /
• v.17 no.2
• /
• pp.161-174
• /
• 2002

To investigate effects of A. gmelini on the 14-day CCl$_4$induced hepatotoxicity, extracts were prepared in 3 ml saline at the dose of 5,000 mg/kg b.w. to administer orally once daily. Each concentration (5：5, 2：5 : 7.5, 1：9, CCl$_4$: olive oil v/v) of CCl$_4$was orally administered with 2.5 ml/kg b.w., During the experiment, halves of the rats were sacrificed every 7 day and hemanalysis was done. On the 7th day, hemanalysis showed following recovery values; AST 52.6∼61.4％, ALT 55.9∼86.1％, ALP 46.0∼70.9%, BUN 75.7∼100.0< ％, TBIL 55.2∼96.1％, TCHO 38.0∼63.7％, and TG 55.2∼96.0％. On the 14th day, recovery values of each treatment were GOT 37.7∼43.1％, GPT 19.8∼45.9％, ALP 58.1∼95.9％, BUN 57.6∼100.0< ％, TBIL 78.6∼100.0< ％, TCHO 56.9∼100.0< ％, and TG 10.0∼5l.2%. By histological examination of liver, hydropic degeneration, fatty change, lipid accumulation and necrosis were also recovered by administration of A. gmelini extract.

• Preventive Nutrition and Food Science
• /
• v.8 no.2
• /
• pp.130-136
• /
• 2003

The protective effects of onion extract (OE), onion powder extracted in ethanol for 2 days. on carbon tetrachloride ($CCl_4$)-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with OE prior to the administration of $CCl_4$ significantly reduced the increase in serum alanine and aspartate aminotransferase activities and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with OE significantly prevented the depletion of reduced glutathione content in the liver of $CCl_4$-intoxicated mice. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic findings. The effects of OE on the cytochrome P450 (P450) 2E1, the major isozyme involved in $CCl_4$ biotransformation were investigated. Treatment of mice with OE resulted in a significant decrease in P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. OE also exhibited antioxidant effects in FeCl$_2$-ascorbate induced lipid peroxidation in rat liver homogenates and in superoxide radical scavenging activity. These results show that the protective effects of OE against the $CCl_4$-induced hepatotoxicity may be due to its ability to block bioactivation of $CCl_4$, mainly tty inhibiting the expression and activities of P450 2E1 and by scavenging free radicals.

• Nutrition Research and Practice
• /
• v.2 no.2
• /
• pp.134-137
• /
• 2008

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

• Journal of the Korean Chemical Society
• /
• v.36 no.2
• /
• pp.185-190
• /
• 1992

Near-IR spectra for $ν_{\alpha}$+ Amide Ⅱ combination band of thioamides, and very dilute thioamide-DMSO solution in CCl4 were recorded in the temperature range of $5^{\circ}C$ to $55^{\circ}C$. This combination band was resolved by the computer program into two Lorentzian-Gaussian product function which have been identified with monomeric thioamide and thioamide-DMSO 1 : 1 complex. Equilibrium constants and thermodynamic parameters for the thioamide-DMSO hydrogen bonding were elucidated by the analysis of conce ntration and temperature dependent spectra. The hydrogen bonding strength between thioacetamide (TA) and DMSO in $CCl_4$ is stronger than that between thiopropionamide (TPA) and DMSO in CCl4. The ${\Delta}H^{\circ}$ for the TA-DMSO and TPA-DMSO 1 : 1 complex in CCl4 were -15.3 kJ${\cdot}$$mol^{-1}$ and -14.2 kj${\cdot}$$mol^{-1}$, respectively.

• Journal of Life Science
• /
• v.27 no.8
• /
• pp.896-901
• /
• 2017

This study was performed to investigate the protective effects of succinic acid of Succiniter against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. After an adaptation period of one week, Sprague-Dawley rats were administered succinic acid of Succiniter at 200 mg/kg every day for 21 days. Then $CCl_4$ (3.3 ml/kg) was intraperitoneally injected into rats of the other groups except the normal group, five hours after the last treatment of succinic acid of Succiniter on day 21. The succinic acid-treated group showed 93.20% and 88.76% of inhibitory effects in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, respectively, compared with the $CCl_4-treated$ group. The succinic acid-treated group showed inhibition of malonedialdehyde (MDA) by 85.17% compared with the $CCl_4-treated$ group. The succinic acid-treated group in liver homogenate promoted effects of 38.65% and 47.99% in superoxide dismutase (SOD) and catalase (CAT), respectively, compared with the $CCl_4-treated$ group. In conclusion, the AST and ALT activities of the succinic acid-treated group were both decreased compared with the $CCl_4-treated$ group. The MDA level of the succinic acid-treated group was decreased compared with the $CCl_4-treated$ group. However, the SOD and CAT levels of the succinic acid-treated group in liver homogenate were both increased compared with the $CCl_4-treated$ group. Also, histological examinations showed that the liver cell necrosis and centrilobular congestion aggregation induced by $CCl_4$ were clearly eliminated by treatment with succinic acid of Succiniter. These results suggest that succinic acid of Succiniter has a protective effect against liver damage and could be used in the development of the appropriate drug.