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Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating Spotl4 and Cyp2e1 expression levels

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Frontiers of Medicine 2019年第1期13卷 104-111页

作者： Xiaofang Cui Benting Ma Yan Wang Yan Chen Chunling Shen Ying Kuang Jian Fei Lungen Lu Zhugang Wang State Key Laboratory of Medical Genomics Research Center for Experimental MedicineRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Research Center for Model Organisms Shanghai 201203China Department of Gastroenterology Shanghai First People s HospitalShanghai Jiao Tong UniversityShanghai 200080China

Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated Rdh13 knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on liver injury induced by carbon tetrachloride (CC14). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the Rdh13^-/- mice displayed an attenuated response to CCl4-induced liver injury. Their livers also exhibited less histological changes and contained lower levels of liver-related metabolism enzymes compared with the livers of wild-type (WT) mice. Furthermore, the Rdhl3 1 mice had Rdh13 deficiency and thus their liver cells were protected from apoptosis, and the quantity of their proliferative cells became lower than that in WT after CC14 exposure. The ablation of Rdhl3 gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (Cyp2el) in the liver, especially after CC14 treatment for 48 h. These data suggested that the alleviated liver damage induced by CC14 in Rdh13^-/- mice was caused by Cyp2el enzymes, which promoted reductive CC14 metabolism by altering the status of thyroxine metabolism. This result further implicated Rdhl3 as a potential drug target in preventing chemically induced liver injury.

关键词： retinol dehydrogenase 13 carbon tetrachloride acute liver injury Cyp2el Spot14

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Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt

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World Journal of Gastroenterology 2013年第43期19卷 7778-7787页

作者： Gang Deng Xiang-Jun Huang Hong-Wu Luo Fei-Zhou Huang Xun-Yang Liu Yong-Heng Wang Department of Hepatobiliary and Pancreatic Surgery the Third Xiangya Hospital of Central South University

AIM:To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride(CCl4).METHODS:Using cre-loxp technique,we created an Ad-myr-HA-Akt virus,in which Akt is labeled by a HA tag and its expression is driven by myr ***,through measuring enzyme levels and histological structure,we determined the efficacy of this Ad-myrHA-Akt virus in inhibiting the development of cirrhosis induced by CCl4in ***,using western blotting,we examined the expression levels and/or phosphorylation status of Akt,apoptotic mediators,endothelial nitric oxide synthase(eNOS),and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this ***:The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment,which was consistent with the sequence reported in the *** concentrations of Admyr-HA-Akt and adenoviral enhanced green fluorescent protein(Ad-EGFP)virus used in the current study were5.5×1011vp/*** portal vein diameter,peak velocity of blood flow,portal blood flow and congestion index were significantly increased in untreated,saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil *** contrast,these parameters in the Akt cirrhosis group were comparable to normal control *** to the normal control,the liver function(Alanine aminotransferase,Aspartate aminotransferase and Albumin)was significantly impaired in the untreated,saline and Ad-EGFP cirrhosis *** Akt cirrhosis group showed significant improvement of liver function when compared to the untreated,saline and Ad-EGFP cirrhosis *** Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis *** results of HE and Van Gieson staining indic

关键词： Adenovirus Akt Gene transfer Apoptosis Cirrhosis Carbon tetrachloride Rat

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Thai Perilla frutescens fruit oil alleviates carbon tetrachloride-induced hepatotoxicities in rats

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Asian Pacific Journal of Tropical Biomedicine 2020年第3期10卷 101-110页

作者： Narisara Paradee Duangta Kanjanapothi Tawat Taesotikul Sarawut Kongkarnka Adchara Prommaban PimpisidKoonyosying Somdet Srichairatanakool Department of Biochemistry Faculty of MedicineChiang Mai UniversityChiang MaiThailand Faculty of Pharmacy Payap University(Maekhao Campus)Chiang MaiThailand Department of Pathology Faculty of MedicineChiang Mai UniversityChiang MaiThailand

Objective:To study the effect of perilla fruit oil against carbon tetrachloride(CCl4)-induced liver damage in ***:Perilla fruit oil was analyzed in terms of fatty acids,tocopherols and tocotrienols using ***-chronic toxicity of perilla fruit oil was investigated in rats for 90 d followed by a 28 d recovery ***,biochemical and pathological parameters were *** evaluate hepatoprotection,rats were divided into five groups and orally administered with Tween 80 for 10 d;Tween 80,silymarin,perilla fruit oil(0.1 mL/200 g)and perilla fruit oil(1 mL/200 g)for 10 d together with subcutaneous injection of CCl4(2 mL/200 g)on days 9 and *** enzymes and pathological parameters were ***:Perilla fruit oil containedα-linolenic acid(56.55%of total fatty acid),β-tocopherol(49.50 mg/kg)andγ-tocotrienol(43.65 mg/kg).Rats showed significant changes in the percentage of monocytes and platelet indices following perilla fruit oil consumption for 90 d;in the percentage of neutrophils and lymphocytes,and RBC indices in the recovery period when compared with the deionized water *** protein and creatinine levels were increased while alkaline phosphatase and aspartate aminotransferase levels were decreased(P<0.05).Organ weight index and pathological indicators did not change *** liver of CCl4-induced rats showed remarkable centrilobular fatty changes,which was ameliorated by perilla fruit oil *** aminotransferase,alanine aminotransferase and alkaline phosphatase levels were decreased(P<0.05)in rats given perilla fruit ***:Perilla fruit oil is rich inα-linolenic acid,β-tocopherol andγ-tocotrienol and improves blood biomarker levels and protects against CCl4-induced *** studies are required before supporting its use for the treatment of hepatitis.

关键词： Perilla frutescens Perilla oil Carbon tetrachloride Fatty change Liver injury

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Phytochemical analysis,hepatoprotective and antioxidant activity of Alchornea cordifolia methanol leaf extract on carbon tetrachloride-induced hepatic damage in rats

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Asian Pacific Journal of Tropical Medicine 2012年第4期5卷 289-293页

作者： Patience O Osadebe Festus BC Okoye Philip F Uzor Nneka R Nnamani Ijeoma E Adiele Nkemakonam C Obiano Department of Pharmaceutical and Medicinal Chemistry Faculty of Pharmaceutical SciencesUniversity of NigeriaNsukka41001Enugu StateNigeria

Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (***) leaf ***:Various solvent fractions of the methanol extract of the leaf of the *** ***(Fam:Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in *** degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/ AST),serum glutamate pyruvate transaminase(SCPT/ALT),alkaline phosphatase(ALP) and total *** in vitro antioxidant activity of the extract was also evaluated by the I,I-diphenyl 2-picrylhydrazyl(DPPH) free radical scavenging *** extract was subjected to preliminary phytoehemical ***:The ethyl acetate and chloroform fractions,at a dose of 300 mg/kg,produced significant(P<0.05) hepatoprolection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the *** effects were comparable to those of the standard drugs used for the respective experiments,silymarin and ascorbic ***,flavonoids,saponins and tannins were delected in the phylochemical ***:From this study,it was concluded that the plant of *** possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.

关键词： Alchornea cordifolia Antioxidant Carbon tetrachloride DPPH model Hepatoprolective Phytochemical analysis

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Hepatoprotective effect of Averrhoea carambola fruit extract on carbon tetrachloride induced hepatotoxicity in mice

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Asian Pacific Journal of Tropical Medicine 2010年第8期3卷 610-613页

作者： A.K.Azeem Molly Mathew Chandraniohan Nair Dilip.C Al Shifa College of Pharmacy Poonthavanam P.OKizhatturPerinlhalmannaMalappuram DistKerala.India 679329 Malik Deenar College of Pharmacy KasaragodKerala Al Shifa College of Pharmacy Poonlhavaimm P.O.KizhatlurPerinthalmannaMalappuram DistKerala.India 679329

Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic ***:Hepatotoxicity was induced on albino mice by intraperitoneal administration of CCl4.half an hour after the administration of the last dose of the extract of Averroha carambola *** extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven *** hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphates（ALP）,glutathione level and histopathological studies of ***:Pre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT,AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride.A marked improvement in the enzyme activities and the liver reduced glulathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analvsis. Conclusions:The aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.

关键词： Averroha carambola Aqueous extract Hepatoprotective activity Carbon tetrachloride

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Curcuma angustifolia ameliorates carbon tetrachloride-induced hepatotoxicity in HepG2 cells and Swiss albino rats

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Asian Pacific Journal of Tropical Medicine 2019年第9期12卷 416-424页

作者： Sudipta Jena Asit Ray Diptirani Rath Ambika Sahoo Subhashree Singh Noohi Nasim Durga Madhab Kar Sanghamitra Nayak Centre.for Botehology Sisha O Anusandhaon(Demed to be UniesiryKalinga NagorGhatiliaBaubeur-750030 OdishaIndia Depurtment of Phuamoacology School of Pharmoceutical SciencesSissha O"Anusondhan(Demed to be Uniersityh Kalinga NagorGhaikiaBhubonesuoar-751003.Odisha India

Objective:To determine the antioxidant and hepatoprotective potential of methanol extract of rhizome of Curcuma angustifolia(MECA)against carbon tetrachloride(CCl4)-induced hepatic damage in vitro and in ***:DPPH,ABTS and reducing power assays were performed to estimate the antioxidant effect of *** vitro cytotoxicity of MECA against HepG2 cells was evaluated,whereas serum biochemical parameters and levels of antioxidative enzymes were measured in vivo and in ***,histopathological studies were estimated in order to investigate the hepatoprotective efficacy of ***,GC-MS analysis of the extract was performed to identify the chemical ***:MECA exhibited strong antioxidant activity and attenuated CCl4-induced decrease in the viability of HepG2 ***,MECA significantly restored the ALT,AST,ALP,TP and albumin level in comparison with the CCl4 *** pre-treatment with MECA,effects of SOD,CAT and GSH were increased as well as lipid peroxidation amount decreased on CCl4-induced hepatotoxicity in in vitro and in vivo ***,histopathological observation confirmed that MECA reduced liver injury induced by CCl4 in ***-MS analysis confirmed the presence of bioactive constituents such as α-tocopherol(12.27%),phytol(7.61%),squalene(3.71%),β-sitosterol(2.19%),eugenol(2.59%),curcumenol(1.20%),β-elemene(1.00%)and eucalyptol(0.89%).Conclusions:MECA contains antioxidant and hepatoprotective constituents such asα-tocopherol,phytol,squalene and eugenol and exerts hepatoprotective effect both in vitro and in vivo.

关键词： Curcuma angustifolia Hepatoprotective activity Carbon tetrachloride Antioxidant activity HepG2 cells

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Hepatoprotective and antioxidant activity of pentagamavunon-0 against carbon tetrachloride-induced hepatic injury in rats

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Asian Pacific Journal of Tropical Medicine 2013年第6期6卷 438-442页

作者： Arief Nurrochmad Supardjan Amir Margono Sardjiman Arief Rahman Hakim Ernawati Erna Kurniawati Erva Fatmawati Department of Pharmacology and Clinical Pharmacy Faculty of PharmacyGadjah Mada UniversitySekip Utara Yogyakarta-55281Indonesia Curcumin Research Center Faculty of PharmacyCadjah Mada UniversitySekip Utara Yogyakarta-55281Indonesia

Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in ***:The groups of animals were administered with PGV-0 at die doses 2.5.5,10,and 20 mg/kg b.w.,*** in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride(CClj)(20%,2 ml/kg *** liquid paraffin dp.).The effect of PGV-0 on serum transaminase(SGPT),alkaline phosphates(ALP and total bilirubin were determined in CCl-4-indueed hepatotoxicity in ***,the effects of PGV-0 on glutathione(GSU) content,cutalase(CAT) and NO free radical scavenging activity also were ***:The results demonstrated that PCV-0 significantly reduced the activity of SGPT,serum ALP and total bilirubin in CCl-4 induced rat ***-0 has effect on the antioxidant and free radical defense *** prevented the depletion level of GSH and decrease activity of CAT in CCl-4-induced liver injury in ***-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM. Convulsion:All of our findings suggests that PGV-0 could protect the liver cells from CCl-4- induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.

关键词： Hepatoprotective Antioxidant Pentagamavunon-0 Carbon tetrachloride Rats

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Protective Effect of Phenolic-Rich Extracts from Different Parts of <i>Opuntia joconostle</i>Fruit against Carbon tetrachloride-Induced Oxidative Stress in Mice

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Journal of Biomaterials and Nanobiotechnology 2013年第3期4卷 35-42页

作者： Obed Osorio-Esquivel Alicia Ortiz-Moreno Julieta Herrera-Martínez María Dolores Hernández-Navarro Departamento de Bioingenieria y Biotecnología Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional México City México Departamento de Farmacia Facultad de Química Universidad Autónoma del Estado de México Toluca México Departamento de Morfología Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional México City México

Opuntia joconostle fruit is a rich source of biocompounds such as polyphenols including gallic, vanilic, 4-hidroxybenzoic, cafeic, and syringic acids, catechin, epicatechin, rutin, and vanillin, besides betalains. The objective of this research was to evaluate the effect of supplementation polyphenols-rich extracts from different parts of Opuntia joconostle against carbon tetrachloride-induced oxidative stress in a mouse model. The animals were treated orally with polyphenols-rich extracts at 50, 100 and 200 mg/kg BW for 30 consecutive days. On day 30th the mice received carbon tetrachloride (CCl4) as hepatoxic agent. Biochemical evaluations were carried out 24 h after induction of the oxidative stress. Data showed that methanolic extracts from different parts of Opuntia joconostle exerting protective effect against the CCl4-induced oxidative stress in mice. Histology examination revealed that the damage decreased in groups treated with polyphenols-rich extracts compared to the group that did not receive any treatment. Opuntia joconostle fruit contains many phenolic compounds, flavonoids and betalains. The protective effect of extracts may be related to the phenolic composition and also by a counteraction with other compounds, such as betalains and flavonoids that increase their antioxidant effect.

关键词： Opuntia joconostle Oxidative Stress Carbon tetrachloride Phenolic Compounds

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Protective effect of juice extract of mesocarp rind of Citrullus lanatus in carbon tetrachloride-induced oxidative stress in rats

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Journal of Coastal Life Medicine 2017年第6期5卷 264-269页

作者： Fisayo Abraham Bamisaye Abdulhakeem Olarewaju Sulyman Emmanuel Oladipo Ajani Aminat Bolanle Muhammed Department of Biochemistry Kwara State UniversityMaleteIlorinNigeria

Objective:To investigate the protective roles of juice extract of mesocarp rind of C. lanatus in carbon tetrachloride-induced oxidative stress in rats. Methods: Thirty albino rats were divided into six groups of 5 animals each, namely Groups A–F. The oxidant (CCl4) was used to induce oxidative stress in rats. It was administered as a single subcutaneous injection (2.0 mL/kg body weight) diluted 1:1 in paraffin oil on the 21st day. Animals in Group A (control) received 1 mL of distilled water;Group B received 1 mL of distilled water + CCl4;Group C received 100 mg/kg body weight ascorbic acid + CCl4;while Groups D, E and F were administered with 50, 100 and 200 mg/kg body weight ofC. lanatus extract + CCl4 respectively. The treatments were given once a day and lasted for 21 days. The levels of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), reduced glutathione (GSH) and malondialdehyde (MDA) in the liver and serum were evaluated. Results:The assessment of antioxidant parameters revealed a significant (P< 0.05) hepatic oxidative damage in CCl4 treated albino rats, and this was considerably reversed to almost normal level in rats co-administered with juice extract of mesocarp rind ofC. lanatus at the dose level of 200 mg/kg body weight/day for 21 consecutive days. Conclusions:It can be concluded from this present study that the mesocarp rind ofC. lanatus is rich in antioxidants and thus suggesting the possibility of utilizing it as nutraceutical or functional foods to prevent or manage some critical complications in living cells.

关键词： Antioxidants Citrullus lanatus Carbon tetrachloride Oxidative stress

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Antihepatotoxic Effect of Feronia Limonia Fruit against Carbon tetrachloride Induced Hepatic Damage in Albino Rats

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Chinese Medicine 2010年第1期1卷 18-22页

作者： Rucha Upadhyay Narendra Deo Pandey Shahid Suhail Narvi Amita Verma Bahar Ahmed Department of Chemistry Motilal Nehru National Institute of Technology Department of Pharmaceutical Chemistry Faculty of Pharmacy Hamdard University

Feronia limonia Swingle, though mentioned as a high utility medicinal plant in Ayurveda for the treat-ment of liver disorders, but has no scientific investigations. Therefore, the present study was undertaken to investigate the hepatoprotective activity of extracts of Feronia limonia fruit on albino rat liver, damage induced by single dose of carbon-tetrachloride (1.5 ml/kg, p.o.). The oral administration of extracts (500 mg/kg, p.o.) for 7 days has shown significant hepatoprotective action. There is reduction in the elevated levels of serum enzymes such SGOT, SGPT, ALP and Serum bilirubin and elevation in level of GSH, GPX,GLY and total protein in Feronia limonia protected rats.

关键词： Anti-Hepatotoxic Carbon tetrachloride Feronia Limonia Swingle

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