• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Journal of Preventive Medicine and Public Health
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• 제24권3호
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 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 $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium 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 long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• 대한한방내과학회지
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• 제29권1호
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• pp.200-218
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• 2008

Objectives : The purpose of this study was to investigate the effects of Injinchunggan-tang (Yinchenchinggan-tang) on DMN-induced liver damage by applying proteomics. Materials and Methods : Sprague-Dawley rats were used in this experiment and were divided into the normal group (normal saline), the control group (DMN) and the sample group (DMN+IJCGT). DMN was injected i.p. once a day three times a week for 3 weeks in the control group. Normal saline instead of DMN was administered to the normal group. In the sample group, Injinchunggan-tang (Yinchenchinggan-tang) extract was orally administered once a day for 10 days after DMN was induced. The livers of each group were processed and analyzed by histology, Western blot, $Oxyblot^{TM}$, CBB and 2-dimensional electrophoresis. Results : In the histological findings of the liver, IJCGT reduced collagen deposition and liver damage in DMN-induced hepatic fibrosis. IJCGT increased MMP-13 protein production assessed by western blot. Protein oxidation induced by DMN treatment was decreased by IJCGT. In the 2-dimensional electrophoresis finding, the level of the increased proteins induced by DMN treatment such as GRP 75, 58kDa glucose regulated protein and heat shock 70kDa protein 5 were decreased by IJCGT. IJCGT was considered to have the protective effects on hepatotoxicity induced by DMN. In the 2-dimensional electrophoresis finding, the level of increased oxidized proteins such as heat shock 70 protein, mitochondrial malonyltransferase, calreticulin precursor, actin, NADP-isocitrate dehydrogenase, ankyrin repeat and SOCS box protein 11 were decreased by IJCGT. IJCGT was considered to have protective effect on the protein production induced by DMN treatment. Conclusion : Injinchunggan-tang (Yinchenchinggan-tang) exerts an inhibitory effect against the fibrosis and protein oxidation induced by DMN treatment in the rat liver. IJCGT was considered to have protective effects on the hepatotoxicity and protein production induced by DMN treatment.

• 한국식품저장유통학회지
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• 제24권1호
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• pp.107-115
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• 2017

동물실험에서 실크단백질 산 가수분해물을 투여하고 t-BHP투여한 군의 혈액 생화학적 검사 결과 t-BHP만 투여한 군과 비교하였을 때 AST, ALT 그리고 LDH가 실크단백질 산 가수분해물의 투여 농도가 높아질수록 수치가 감소하는 것으로 나타났고 세포가 손상할 시에 증가하는 MDA를 간 조직을 대상으로 측정한 결과 실크단백질 산 가수분해물의 농도가 높아질수록 수치가 대조군과 유사한 정도로 감소하는 것으로 보아 간 손상에 관여하는 효소의 누출 억제효과가 있는 것으로 사료된다. HPLC로 간 조직에서의 GSH 측정결과 t-BHP만 투여한 군과 비교하였을 때 유의적으로 증가하였고 조직학적 검사 결과 t-BHP만 투여한 군과 비교하였을 때 실크단백질 산 가수분해물을 투여한 군이 대조군과 가까운 모습을 보이는 것으로 관찰되어 실크단백질 산 가수분해물이 산화적 스트레스로부터의 간 보호 효과가 있는 것으로 사료된다. 따라서 실크단백질 산 가수분해물의 기능적 소재로서의 이용가능성이 확대될 것으로 사료된다.

• Toxicological Research
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• 제23권4호
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• pp.347-352
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• 2007

The protective effects of Rubus coreanum Miquel (RCM) extract against LPS-induced hepatotoxicity were studied in rats. Squrague-Dawley rats were intraperitoneally administered the RCM at 100 mg/kg per day for three weeks. Then single dose of LPS (5 mg/kg) was injected into rats. Four hours later, they were anesthesized with ether and dissected. We examined the levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in sera, superoxide dismutase (SOD) in mitochondrial fraction and catalase (CAT), glutathione peroxidase (GPx) in liver homogenate. LPS-treatment markedly increased the levels of AST, ALT, ALP, LDH and significantly decreased those of SOD, CAT and GPx. But RCM-pretreatment decreased the levels of AST, ALT, ALP and LDH by 57.9%, 37.4%, 62% and 69% respectively and increased those of SOD, CAT and GPx by 82.9%, 64.2% and 96.7% respectively. Subsequently, the protective effects of RCM was evaluated through histopathological examination of liver tissue. The LPS treatment increased the state of necrosis and cirrhosis surrounding the central veins (CV) and sinusoid, but RCM-treatment decreased the state of necrosis and cirrhosis in the liver tissue. These results demonstrated that protective effects of RCM against LPS-induced hepatotoxicity.

• Journal of Preventive Medicine and Public Health
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• 제35권3호
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• pp.221-228
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• 2002

Objectives : The purpose of this study was to find the protective effects of garlic on the halogenated hydrocarbon induced hepatotoxicities, and the possible protection mechanisms involved. Methods : Male Sprague-Dawley rats received garlic (0.5%) or regular diet, for 4 weeks. This was followed by a single dose of corn oil (the controls), carbon tetrachloride (400mg/kg body weight) and trichloroethylene (2,000mg/kg body weight) being administered to each diet group. Blood samples were collected 24 hours fellowing the administration, and the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALD activities measured. The liver samples were studied for their cytochrome P450 and CYP2E1 contents, lipid peroxidation and histopathology. Results : rho results for the group receiving the 9.5% garlic diet showed a slight decrease of CYP2E1 expression compared with the regular diet group. Carbon tetrachloride was significantly decreased the CYP2E1 contents in both the regular and garlic diet groups, but the trichloroethylene remained unchanged. Garlic did not decrease the lipid peroxidation of the liver in the control group, but attenuated the increase of lipid peroxidation caused by carbon tetrachloride. Garlic attenuated the increase of both the serum AST and ALT activities caused by carbon tetrachloride. The histopathelogical observations also showed that garlic attenuated centrilobular necrosis and vacuolar degenerative changes significantly in the carbon tetrachloride treated group. Conclusions : The results indicate that garlic attenuates the carbon tetrachloride-induced hepatotoxicity, through the prevention of the metabolic activation and lipid peroxidation.

• 동의생리병리학회지
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• 제25권4호
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• pp.663-668
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• 2011

Galgeun-tang (GGT) has been a great source for treating cold diseases in the folk medicine recipe. Carbon tetrachloride ($CCl_4$) is one type of hepatotoxin that can eventually cause liver injury. During the experiment, we first studied the protective effects of GGT against $CC_4$-induced hepatotoxicity. GGT was pretreated for 3 h, and 1% $CCl_4$ was added to mouse primary liver cells. After 4 h, ROS generation and expression of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) were analyzed by FACS and real time PCR. Also, the activities of ALT and LDH were measured using cultured medium. The hepatic levels of TNF-alpha and iNOS, which are related to inflammation and stress response gene, HSP72 and HO-1 were analyzed by PCR or real time PCR. Liver tissues were analyzed by HE stain. From the observation, we discovered that GGT treatment protects $CCl_4$-induced hepatotoxicity, and that GGT pretreatment decreases ROS generation, TNF-alpha and iNOS expression. However, gene expression of CAT, SOD, GPx, HSP72 and HO-1 were increased by GGT. These results lead to the conclusion that GGT has protective effects against $CCl_4$-induced hepatotoxicity.

• 한국식품영양과학회지
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• 제40권8호
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• pp.1107-1112
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• 2011

본 연구는 기존에 알코올 해독 기능이 우수한 것으로 알려진 헛개나무 열매 추출물과 헛개나무 열매 추출물을 주성분으로 하여 매실 및 댕댕이나무 열매 추출물이 혼합되어진 새로운 식품 조성물의 항알코올 기능에 대한 효능을 비교 분석함으로써 새로운 알코올 독성 경감 소재를 개발하고자 하였다. 새로운 식품 조성물인 SAC-1을 흰쥐에게 투여한 후 알코올을 섭취시켰을 때 혈중 알코올 농노의 저하가 헛개나무 추출물에 비하여 매우 우수한 효능이 있는 것으로 나타났으며, 간손상의 지표인 GOT, GPT에 있어서 대조군에 비하여 낮은 값을 나타내어 알코올에 의한 간손상을 경감시킬 수 있는 것으로 생각된다. 또한, 조직에서 산화적 손상으로 효능을 살펴본 결과는 지질과산화물의 생성을 혈장과 간 조직에서 모두 억제하는 것으로 나타났으며, total glutathione의 감소를 억제하는 것으로 나타나 SAC-1은 알코올성 조직 손상에서 충분한 보호 작용을 나타낼 수 있었던 것으로 생각된다. 특히 SAC-1은 헛개나무 열매 추출물 단독 사용에 비해서 더 높은 활성을 나타낸 것으로 나타났으며, 이것은 SAC-1이 알코올 해독에 좋은 천연 성분을 함유하고 있는 결과로 추측된다. 이상의 결과에서 SAC-1은 알코올로 인해 유도되어지는 조직 손상 및 숙취 증상으로부터 조직을 보호할 수 있는 능력이 있는 것으로 생각된다.

• Journal of Ginseng Research
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• 제35권2호
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• pp.243-249
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• 2011

Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has a variety of biological properties, including anti-inflammatory, antioxidant and anticancer effects. Aflatoxin $B_1$ ($AFB_1$) produced by the Aspergillus spp. causes acute hepatotoxicity by lipid peroxidation and oxidative DNA damage, and induces liver carcinoma in humans and laboratory animals. This study was performed to examine the protective effects of KRG against hepatotoxicity induced by $AFB_1$ using liver-specific serum marker analysis, histopathology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In addition, to elucidate the possible mechanism of hepatoprotective effects, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were analyzed. Rats were treated with 250 mg/kg of KRG (KRG group) or saline ($AFB_1$ group) for 4 weeks and then received 150 ${\mu}g/kg$ of $AFB_1$ intraperitoneally for 3 days. Rats were sacrificed at 12 h, 24 h, 48 h, 72 h, or 1 wk after $AFB_1$ treatment. In the KRG pre-treatment group, serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels were low, but superoxide dismutase, catalase, and glutathione peroxidase activities were high as compared to the $AFB_1$ alone group. Histopathologically, $AFB_1$ treatment induced necrosis and apoptosis in hepatocytes, and led to inflammatory cells infiltration in the liver. KRG pre-treatment ameliorated these changes. These results indicate that KRG may have protective effects against hepatotoxicity induced by $AFB_1$ that involve the antioxidant properties of KRG.

• 약학회지
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• 제43권6호
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• pp.827-833
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• 1999

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.