• 한국임상수의학회지
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• 제30권1호
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• pp.12-16
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• 2013

This study was performed to investigate hepatoprotective effect of rutin on acute hepatic damage induced by carbon tetrachloride in rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups; normal control group, $CCl_4$ control group, two rutin treatment groups (rutin 200+$CCl_4$ and rutin 400+$CCl_4$). Dissolving vehicles were applied to the rats in the normal control group. The rutin was administrated to the rats in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups at the levels of 200 mg/kg and 400 mg/kg, 3 consecutive days orally, with 24 hours interval before inoculating $CCl_4$. $CCl_4$ was intraperitoneally administered an hour after the last treatment of rutin to the rats in every group except the normal control group. The body weight of rats in $CCl_4$ control group were significantly lower than other groups (p < 0.05), but the liver weight and relative liver weight were higher than normal control group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in sera of rats in $CCl_4$ control group were higher and the levels of total protein, albumin and globulin were lower than the normal group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups were lower than $CCl_4$ control group (p < 0.05). Therefore the pre-treatment of rutin before $CCl_4$ inoculation in rats effectively inhibited the elevation of serum ALT, AST and total bilirubin which are the parameters of hepatic damage.

• Toxicological Research
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• 제11권2호
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• pp.247-252
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• 1995

To evaluate the effect of xanthine oxidase on liver injury by $CCl_4$, liver damage was induced both in allopurinol pretreated rats (500 mg/kg. ip) and control group by twice intraperitoneal injection of $CCl_4$ (0.1 ml/100 g body wt. 50% in olive oil) at interval of one day. Increases in the levels of serum alanine aminotransferase and liver weight/body weight (%) by $CCl_4$ were significantly smaller inallopurinol pretreated rats than in control whereas the hepatic microsomal glucose-6-pholphatase activities were significantly higher in allopurinol pretreated rats than control group by $CCl_4$ treatment. These results indicates that allopurinol pretreatment may reduce the liver damage in $CCl_4$ intoxicated rats. In rats either with $CCl_4$or not, hepatic type O xanthine oxidase activities were significantly reduced by allopurinol pretreatment and the increasing rate of these enzymes to each control was remarkably lower in allopurinol pretreated rats than control. Liver cytosolic protein contents and aniline hydroxylase, aminopyrine demethylase activities were higher in allopurinol pretreated rats than coirol rats when animals were treated with $CCl_4$. On the other hand, neither allopurinol pretreated nor $CCl_4$ treatment caused any significant changes in hepatic superoxide dismutase and catalase activities. Hepatic glutathione contents were higher in $CCl_4$-treated rats than control, but no significant changes were found in both between the allopurinol treated rats and $CCl_4$-treated rats pretreated with allopurinol, and glutathione and glutathione S-transferase activities were significantly reduced in $CCl_4$-treated rats than control whereas these enzyme activities showed on significant change in both between allopurinel treated and $CCl_4$-treated rats pretreated with allopurinol. It is concluded that xanthine oxidase reaction system augment $CCl_4$ induced liver injury via even oxygen free radical system.

• 생명과학회지
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• 제27권8호
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• pp.896-901
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• 2017

본 연구는 $CCl_4$로 간 손상이 유도된 흰 쥐에서 호박산의 간 보호 효과 정도를 알아보기 위하여 수행되었다. 실험을 하기 위해 정상군(NOR), $CCl_4$처리군(CON), 보석호박섭취군(PCON-CS)군으로 나누어 1주일 적응기간을 가진 SD계 흰 쥐에 보석호박산을 일정한 시간에 200 mg/kg으로 3주간 투여하였다. 21일째 되는 날 마지막 투여 5시간 후에 정상군을 제외한 다른 그룹의 쥐에게 $CCl_4$를 복강주사 하였다. 보석호박섭취군은 $CCl_4$처리군에 비해 AST, ALT 활성은 93.20%, 88.76% 각각 억제효과를 보였고 MDA는 $CCl_4$처리군에 비해 85.17% 억제효과를 보였다. 보석호박섭취군의 SOD와 CAT는 $CCl_4$처리군에 비해 38.65%, 47.99% 증가효과를 보였다, 결론적으로 AST, ALT 활성도와 MDA 수치는 보석호박섭취군이 $CCl_4$처리군에 비하여 유의적으로 감소하여 정상군과 비슷한 수치를 나타내었고 SOD와 CAT효소 활성은 보석호박섭취군이 $CCl_4$처리군에 비하여 증가하였다. 또한 조직학적 관찰은 사염화탄소로 유도된 간경변과 세포괴사가 호박산에 의해 예방된 것으로 나타났다. 이 데이터들로 확인해보면 $CCl_4$로 유도된 간 독성을 호박산이 간을 보호하는 결과를 나타냈으며, 이는 호박산이 간 손상에 대한 보호 효과를 가진 약물의 소재개발에 이용 될 수 있다고 본다.

• Toxicological Research
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• 제19권2호
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• pp.105-114
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• 2003

TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.

• 한국환경보건학회지
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• 제29권2호
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• pp.80-86
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• 2003

To evaluate the effect of cyclohexane(CH) treatment on the serum levels of glutathion S-transferase(GST) activity in liver damaged animals, damaged liver was induced with pretreatment of 50% $CCl_4$ dissolved in olive oil (0.1 m1/100g body weight) intraperitoneally 17 times every other day. To $CCl_4$-treated rats, CH (1.56 g/kg body weight, i.p) was injected once and then the animals were sacrificed at 4 hours after injection of CH. The $CCl_4$-treated animals were identified as severe liver damage on the basis of liver functional findings, 1,e, increased serum levels of alanine aminotransferase(ALT), alkaline phosphate(ALP) and xanthine oxidase(XO) activities. On the other hand, $CCl_4$-treated animals injected with CH once($CCl_4$-pretreated animals) showed more decreased serum levels of ALT and XO, and more increased those of ALP rather than $CCl_4$-treated animals. In case of comparing the GST with ALT activity in liver, both $CCl_4$-treated and pretreated animals showed similar changing pattern of enzyme actvity. Especially $CCl_4$-pretreated animals showed significantly increased serum level of GST actvity compared with the $CCl_4$-treated those, whereas those of ALT showed reversed tendency. In aspects of GST enzyme kinetics, $CCl_4$-pretreated animals showed higher Vmax of liver GST enzyme than $CCl_4$-treated animals. In conclusion, injection of CH to the liver damaged rats led to enhanced liver damage and more increased activity of serum GST which may be chiefly caused by the enzyme induction.

• 생약학회지
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• 제25권4호통권99호
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• pp.388-394
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• 1994

80% Methanol extracts of 44 traditional drugs used for the treatment of liver diseases or tonic effects were screened for anti-hepatotoxic activity by in vitro assay using $CCl_4-induced$ cytotoxicity in primary cultured rat hepatocytes. $CCl_4-induced$ cytotoxicity was evaluated by determination of LDH, GOT or GPT activity in the medium. Rehmaniae Radix Preparata and Gelantina nigra inhibited the release of LDH, GOT or GPT from $CCl_4-treated$ hepatocytes. Gibotii Rhizoma and Eucommiae Cortex showed inhibitory effect on release of LDH from normal hepatocytes as well as $CCl_4-treated$ hepatocytes. Eucommiae Cortex and Lili Bulbus decreased release of GOT and LDH from normal hepatocytes, respectively. Astragali Radix inhibited release of GPT in $CCl_4-treated$ hepatocytes. Phlomidis Radix, Imperatae Rhizoma, Cistanchis Herba, Broussonetiae Fructus, Asparagi Tuber, Trigonellae Semen and Polgonati Rhizoma inhibited release of LDH from $CCl_4-treated$ hepatocytes. Among 44 traditional drugs, most of them released LDH, GOT or GPT at the dose of 1 mg/ml in normal hepatocytes, and Drynariae Rhizoma, Acanthopanacis Cortex, Longanae Arillus, Atratylodis Rhizoma and Ecliptae Herba increased $CCl_4-induced$ cytotoxicity.

• 대한의생명과학회지
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• 제8권1호
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• pp.47-52
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• 2002

To investigate an effect of cyclohexanone (CHO) treatment on the serum levels of xanthine oxidase (XO) in liver damaged animals, the rats were intraperitoneally pretreated with 50% carbon tetrachloride ($CCl_4$) in olive oil (0.1 mL/ 100 g body weight) 14 times every other day. To the $CCl_4$-pretreated rats, CHO (1.56 g/kg body weight) was injected once and then the animals were sacrificed at 4 hours after CHO treatment. The increasing rate of serum and liver XO activities to the control was higher in CHO-treated animals pretreated with $CCl_4$ than the $CCl_4$-pretreated those. Concomitantly CHO injection to the $CCl_4$-pretreated animals showed somewhat higher Vmax and lower Km value in the kinetics of liver XO enzyme. Furthermore, increasing rate of hepatic malonedialdehyde content to the control was also higher in CHO-treated animals pretreated with $CCl_4$ than $CCl_4$-pretreated those. On the other hand, the injection of CHO to the $CCl_4$-pretreated animals showed the more enhanced liver damage on the basis of liver function finding; liver weight per body weight (%), serum levels of alanine aminotransferase activity and hepatic glucose-6-phosphatase activity. In conclusion, injection of CHO to the $CCl_4$-pretreated rats led to more increased activity of serum XO and it may be caused by acceleration of hepatocyte membrane permeability and induction of enzyme protein.

• 생약학회지
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• 제26권1호
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• pp.51-56
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• 1995

To devise an in vitro screening method for antihepatotoxic activity, $CCl_4-induced$ cytotoxicities in primary cultures rat hepatocytes were examined. When rat hepatocytes were intoxicated with 0.5, 1.0 or 1.5 mM $CCl_4$ for 1.5, 3 or 19hr, in order of LDH>GOT>GPT release form hepatocytes was increased in a dose-dependent manner. Treatment with 1.5 mM $CCl_4$ for 1.5 hr showed maximum increase in activity of LDH, GOT or GPT released in the medium compared with the control. At this experimental condition, well known antihepatotoxic substances, glycyrrhizin and silybin markedly inhibited $CCl_4-induced$ cytotoxicities. These results demonstrated that the screening method using $CCl_4-induced$ injury in primary cultured rat hepatocytes might be suitable in vitro assay for antihepatotoxic activity.

• 한국식품영양과학회지
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• 제20권6호
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• pp.527-537
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• 1991

To evaluate an effect of liver xanthine oxidase on the induction of liver damage, carbon tetrachloride (CCl4) was intraperitoneally injected twice at 0.1ml/100g body weight to the rate fed a low (LP)or high protein diet(HP) while the control group fed LP or HP received only olive oil. The changing rate of liver xanthine oxidas activity was compared with that of a free radical generating enzyme, liver aniline hydroxylase and a scavenging enzyme, glutathions S-transferase activity between the rate fed a LP and those fed HP, and the two groups treated with CCl4. Concomitantly, the degree of liver damage which could be considered as the paramete for CCl4 metabolism in case of CCl4-intoxicated animal was observed in the present experimental conditions and the effect of allopurinol, xanthine oxidase inhibitor, on the CCl4-toxicity of rate liver was alos demostrated. On the other hand, the comparative effect of actinomycin D on the liver and serum xanthine oxidase of CCl4-treated rats fed HP with that of those fed LP and the kinetics of purifed liver enzyme from the liver of CCl4-treated rats fed HP was also compared with that of those fed LP to clarify the differences of xanthine oxidase activity between two groups. The increasing rate of liver weigth/body wt, serum levels of ALT and the decreasing rate of hepatic ALT activity and protein contents to each control group were higher in CCl4-treated rats fed HP than those fed LP. Under the animal models as indentified by the present data herein, the liver xanthine oxidase activity was higher in CCl4-treated rats fed HP than those fed LP, and the control group fed HP also showed the much higher activity xanthine oxidase than that fed LP, whereas there were no differences in the activity of hepatic aniline hydroxylase and glutathions S-transferase between the two group treated with CCl4. Although the hepatic aniline hydroxylase activity was somewhat higher in the rats fed HP than those fed LP, the increasing rate of liver xanthine oxidase to the rats fed LP was higher in those fed HP than that of liver aniline hydroxylase. The degree of liver damage identified such as liver weight and serum ALT activity was less in the CCl4-treated rats pretreated with allopurinol. These results suggest that even a system at which xanthine oxidase acts as well as the drug metabolizing enzyme may influence the acelatin of CCl4 metabolism. In addition, the purified liver xanthine oxidase from CCl4-treated rats fed HP showed decreased Km value when compared to its control group. The Km value of liver xanthine oxidase of CCl4-treated rats fed LP showed a similar Km value with its control group. Furthermore, the decreasing rate of liver and serum xanthine oxidase acitivity in CCl4-treated rats pretreated with actinomycin D to the CCl4-treated rats was higher in rats fed HP than in those fed LP. These results suggest that the inductino of xanthine oxidase in CCl4-treated rats fed HP may be greater than in those fed LP.

• The Korean Journal of Pain
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• 제21권3호
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• pp.187-196
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• 2008

Background: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. Methods: We measured changes in mechanical and thermal sensitivity in the hind paws of naïve rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. Results: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. Conclusions: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.