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Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

World Journal of Hepatology 2013年第7期5卷 379-386页

作者： mirandeli bautista María ngeles Gómez del Rio Juana Benedí María Isabel Sánchez-Reus José A Morales-González Ana María Téllez-López Maricela López-Orozco rea Académica de Farmacia Instituto de Ciencias de la Salud Universidad Autónoma del Estado de Hidalgo Departamento de Bioquímica y Biología Molecular Facultad de Farmacia Ciudad Universitaria Departamento de Farmacología Facultad de Farmacia Ciudad Universitaria Escuela Superior de Medicina Instituto Politécnico Nacional

AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.

关键词： Dichloromethylene diphosphonate Kupffer cells Thioacetamide Hepatotoxicity Cell cycle

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Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

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World Journal of Gastroenterology 2015年第25期21卷 7718-7729页

作者： Eduardo Madrigal-Santillán mirandeli bautista Juan A Gayosso-De-Lucio Yadira Reyes-Rosales Araceli Posadas-Mondragón ángel Morales-González Marvin A Soriano-Ursúa Jazmín García-Machorro Eduardo Madrigal-Bujaidar Iselaálvarez-González JoséA Morales-González Laboratorio de Medicina de Conservación Escuela Superior de MedicinaInstituto Politécnico NacionalPlan de San Luis y Díaz MirónMéxico DF 11340México área Académica de Farmacia ICSaUniversidad Autónoma del Estado de HidalgoPachuca de Sotoestado de HidalgoCP 42000México Escuela Superior de Cómputo Instituto Politécnico NacionalAv.Juan de Dios Bátiz s/n esquina Miguel Othón de MendizabalUnidad Profesional Adolfo López Mateos Departamento de Fisiología Escuela Superior de MedicinaInstituto Politécnico NacionalPlan de San Luis y Díaz MirónColonia Casco de Santo TomasDel.Miguel HidalgoMéxico DF 11340México Laboratorio de Genética Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalAv.Wilfrido MassieuUnidad A.López MateosZacatencoMéxico DF 07700México

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was ***: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 5

关键词： Geranium schiedeanum Liver regeneration Ethanol Free radicals Nuclear factor erythroid-2-relatedfactor 2

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Review of natural products with hepatoprotective effects

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World Journal of Gastroenterology 2014年第40期20卷 14787-14804页

作者： Eduardo Madrigal-Santillán Eduardo Madrigal-Bujaidar Isela álvarez-González María Teresa Sumaya-Martínez José Gutiérrez-Salinas mirandeli bautista ángel Morales-González Manuel García-Luna y González-Rubio J Leopoldo Aguilar-Faisal José A Morales-González Laboratorio Medicina de Conservación Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón Col. Casco de Santo Tomás Del. Miguel Hidalgo México DF 11340 México Laboratorio de Genética Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional Unidad profesional Adolfo López Mateos Col. Lindavista Delegación Gustavo A. Madero México DF 07738 México Secretaria de Investigación y Estudios de Posgrado Universidad Autónoma de Nayarit "Ciu-dad de la Cultura Amado Nervo" Nayarit 28000 México Laboratorio de Bioquímica y Medicina Experimental División de Investigación Biomédica Centro Médico Nacional "20 de Noviembre" ISSSTE México DF 03100 México área Académica de Farmacia Instituto de Ciencias de la Salud UAEH Pachuca Hidalgo 42000 México Escuela Superior de Cómputo Instituto Politécnico Nacional Av. Juan de Dios Bátiz s/n esquina Miguel Othón de Mendizabal Unidad Profesional Adolfo López Mateos México DF 07738 Mexico Facultad de Odontología UNAM México DF 04510 Mexico

The liver is one of the most important organs in the body,performing a fundamental role in the regulationof diverse processes,among which the metabolism,secretion,storage,and detoxification of endogenous and exogenous substances are *** to these functions,hepatic diseases continue to be among the main threats to public health,and they remain problems throughout the *** enormous advances in modern medicine,there are no completely effective drugs that stimulate hepatic function,that offer complete protection of the organ,or that help to regenerate hepatic ***,it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases,with the aim of these alternatives being more effective and less *** use of some plants and the consumption of different fruits have played basic roles in human health care,and diverse scientific investigations have indicated that,in those plants and fruits so identified,their beneficial effects can be attributed to the presence of chemical compounds that are called *** present review had as its objective the collecting of data based on research conducted into some fruits(grapefruit,cranberries,and grapes)and plants[cactus pear(nopal)and cactus pear fruit,chamomile,silymarin,and spirulina],which are consumed frequently by humans and which have demonstrated hepatoprotective capacity,as well as an analysis of a resin(propolis)and some phytochemicals extracted from fruits,plants,yeasts,and algae,which have been evaluated in different models of hepatotoxicity.

关键词： Hepatoprotection Grapefruit Vaccinium spp Vitis vinifera L Opuntia ficus-indica Spirulina Propolis Glucans Alcoholic liver disease

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