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<b>Background and Objective:</b> Paracetamol does not cause toxic effects if given in therapeutic doses, namely below 4 g per day. Use of paracetamol at a dose of more than 4 g per day can result in hepatotoxicity. This study aims to compare the hepatoprotector potency of the ethanol extract of soursop stem bark (<i>A. muricata</i>) against the enzyme activity of SGOT and SGPT in rats induced by toxic doses of paracetamol. <b>Materials and Methods:</b> A Completely Randomized Design (CRD) comprised of 6 treatment groups and 3 replications. Total 27 white male rats were induced hepatotoxicity with 1350 mg of paracetamol on the 7th day, except for normal control (K0) which was given aquadest. The tested animals received akuades as the negative control (K-) 11.34 mg kg¹ b.wt., of Hepa-Q as the positive control (K+), ethanol extract stem bark <i>Annona muricata</i> at a dose of 150 mg kg¹ BB (P1), 300 mg kg¹ BB (P2) and 600 mg kg¹ BB (P3). <b>Results:</b> There was a significant difference (p<0.05) in the levels of SGOT and SGPT after giving ethanol extract of soursop (<i>A. muricata</i>) stem bark. The best treatment for reducing SGOT and SGPT levels in rats induced by paracetamol was the administration of ethanol extract of <i>A. muricata</i> stem bark at a dose of 600 mg kg¹ BB. <b>Conclusion:</b> Based on the results of the study, it was concluded that all ethanol extract of <i>Annona muricata</i> L. stem bark (EEAMSB) doses had the potential to reduce the levels of AST and ALT in paracetamol-induced rats.

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R-(+)-limonene is a monoterpene from plants of the genus Citrus with diverse biological properties. This research evaluated the effects of dietary supplementation with R-(+)-limonene on growth, metabolic parameters in plasma and liver, and the antioxidant and stress responses in silver catfish, Rhamdia quelen, challenged or not with Aeromonas hydrophila. Fish were fed for 67 days with different doses of R-(+)-limonene in the diet (control 0.0, L0.5, L1.0, and L2.0 mL/kg of diet). On the 60th day, a challenge with A. hydrophila was performed. R-(+)-limonene in the diet potentiated the productive performance of the fish. The metabolic and antioxidant responses indicate that R-(+)-limonene did not harm the health of the animals and made them more resistant to the bacterial challenge. Histological findings showed the hepatoprotective effect of dietary R-(+)-limonene against A. hydrophila. Igf1 mRNA levels were upregulated in the liver of fish fed with an L2.0 diet but downregulated with bacterial challenge. The expression levels of crh mRNA were higher in the brains of fish fed with the L2.0 diet. However, the L2.0 diet downregulated crh and hspa12a mRNA expression in the brains of infected fish. In conclusion, the results indicated that R-(+)-limonene can be considered a good dietary supplement for silver catfish.

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The liver is extremely vulnerable to damage because of its role in metabolism. Toxin, metabolic syndrome, alcohol, microorganisms, and autoimmune diseases can be the cause of liver damage. While different etiologies can cause liver disease, pathophysiologically, there are similarities in the role of free radicals, inflammatory mediators, and gut microbiome during the disease development. Therefore, ingredients with antioxidant, antiinflammatory, and antidysbiotic properties have the potential to act as hepatoprotectors; and water kefir is one of them. Water kefir is a traditional fermented drink made from water kefir grains, sugar, and dried fruit. Water kefir is dominated by lactic acid bacteria and yeast as a fermented beverage, and several species of this group of microorganisms have been shown as probiotics. According to researches, water kefir has strong antioxidant, antiinflammatory, and hepatoprotective effects. Even so, there are still few researches reported about water kefir as a hepatoprotective agent. Several studies, on the other hand, showed promising results. This review discusses the relationship between the pathophysiology of liver disease and the pharmacological activity of water kefir and other probiotics in general, which leads to the potential prospect of water kefir research as a hepatoprotective agent.

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INTRODUCTION AND AIMS: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. MATERIALS AND METHODS: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. RESULTS: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. CONCLUSION: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.

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OBJECTIVE: The aim: To investigate the effectiveness of complex protocol treatment with the additional inclusion of a course of the sublingual form of hepatoprotector on the clinical manifestations of patients with chronic pancreatitis in combination with type 2 diabetes mellitus. PATIENTS AND METHODS: Materials and methods: We studied 57 outpatients with chronic pancreatitis in the phase of stable or unstable remission in combination with diabetes mellitus in the phase of stable or unstable remission. Two groups were formed according to randomization principles to study the effectiveness of the proposed correction programs: 1stgroup (30 patients) took protocol treatment for one month, 2nd group (27 patients) - received protocol treatment with a course of hepatoprotector. RESULTS: Results: It was found the results of the impact of two treatment programs on some clinical symptoms and syndromes in patients with chronic pancreatitis. Positive dynamics of clinical symptoms/syndromes were found in both groups of patients, but the therapeutic effect in the 2nd group was more significant. Analysis of the dynamics of the Quality of Life parameters on the scales of a specialized gastroenterological questionnaire under the influence of two treatment programs found statistically significant (p<0.05) changes in the group with the inclusion of hepatoprotector for treatment for all parameters in contrast to the group of protocol treatment, where statistically significant changes on three scales (abdominal pain, gastric reflux, and dyspepsia). CONCLUSION: Conclusions: It is proved that the proposed inclusion in the protocol treatment of a combination of CP and DM2 course of sublingual a demethion in eledtoan increase in its effectiveness in the correction of abdominal pain - by 8.2%, dyspepsia - by 17.8%, constipation - by 7.4% , diarrhea - by 12.9%, astheno-neurotic - by 21.5%, allergic - by 15.9%, autonomic - by 20.1% (p<0.05). Found higher efficacy of treatment with the in clusion of a demethion in relation to that in the group of PL on the dynamics of the parameters of the scales of the GSRS questionnaire by a total of 13.7%, p <0.01: abdominal pain decreased by 22.6% vs. 16.7%, gastricreflux - by 34.7% against 16.9% (p <0.05), diarrhea - by 23.9% against 8.2% (p<0.001), constipation - by 20.6% against 5.9% (0.01), dyspepsia - by 32.4% against 17.9% (p <0.01), respectively. It proved the feasibility of using sublingual demethion in the complex rehabilitation treatment of patients with comorbidity of CP and diabetes mellitus in order to correct clinical symptoms.

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BACKGROUND: Hepatopathies are an important group of disorders in dogs where proper nutritional care is crucial. Supplementation with a hepatoprotectant like silybin can improve liver function and should not interfere with nutrient digestibility. The purpose of this study was to investigate the effect of both pure silybin and commercial hepatoprotectant on nutrients digestibility, liver function indices and health status in healthy dogs (EXP1). Moreover, the second experiment (EXP2) investigated the effect of commercial hepatoprotectant on liver function tests and liver-associated miRNAs concentration in dogs with idiopathic liver disorder. RESULTS: Nutrient digestibility was not affected by treatment in EXP1. Supplementation did alter the serum fatty acid profile, with no clinical relevance. The levels of liver markers such as ALT, AST and GGT significantly decreased. In EXP2, supplementation with commercial hepatoprotectant containing silybin improved liver function tests. A decrease was observed in liver serum markers such as ALT, AST and miR122 concentration. CONCLUSIONS: EXP1 confirmed that silybin (whether pure or as a commercial hepatoprotectant) does not interfere with digestion which subsequently exerts no detrimental effect on dogs' health and metabolism. In EXP2, dietary supplementation with commercial hepatoprotectant containing silybin resulted in a decreased activity of serum liver markers, accompanied by a decrease in the concentration of liver-specific miRNA molecules. Liver function indices were consequently improved. Silybin supplementation can thus serve as an effective therapeutical tool in dogs with hepatopathies.

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OBJECTIVE: The aim: Of this research is to evaluate laboratory changes in the liver blood tests, carbohydrate and lipid metabolism in NAFLD patients with concomitant pre-diabetes, and to study the feasibility of their complex treatment with the inclusion of omega-3 polyunsaturated fatty acids and essential phospholipids. PATIENTS AND METHODS: Materials and methods: We have examined 55 patients with non-alcoholic fatty liver disease on the background of pre-diabetes aged 40 to 75 years. Modification of lifestyle was recommended to all patients as a basic treatment. In addition, the patients were prescribed essential phospholipids in 2 capsules 3 times a day and omega-3 polyunsaturated fatty acids 1000 mg per day for 28 patients (group 1) or rosuvastatin 10 mg per day for 27 persons (group 2). The effectiveness of the treatment was evaluated in 3 months, and the long-term outcomes were evaluated in 12 months. RESULTS: Results: Under the influence of the prescribed treatment, a hypolipidemic effect was observed in both groups, but a significant decline in the activity of alanine aminotransferase and aspartate aminotransferase occurred only under the influence of a combination of essential phospholipids and omega-3 polyunsaturated fatty acids. CONCLUSION: Conclusions: Thus, the described results allow to recommend this combination of medicines to patients with non-alcoholic fatty liver disease and concomitant pre-diabetes.

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Resumo A homeopatia pode ser utilizada na pecuária leiteira como uma alternativa segura aos antibióticos, capaz de reduzir a expansão da resistência microbiana, ao passo que mantém a saúde dos rebanhos. No entanto, os compostos homeopáticos podem também ser usados como protetores do fígado, podendo atuar na modulação da função hepática. Os medicamentos homeopáticos a base de plantas podem ser utilizados como agentes hepatoprotetores, uma vez que possuem a capacidade de prevenir e reparar desordens hepáticas que comumente acometem vacas em lactação. Assim, o conhecimento das propriedades terapêuticas de plantas permite a elaboração de preparos homeopáticos, capazes de preservar a saúde dos animais de produção. Baseado nisso, objetivou-se com esta revisão discorrer sobre compostos vegetais utilizados na homeopatia como hepatoprotetores e seus efeitos no metabolismo hepático e na resposta produtiva de animais ruminantes em lactação.

Abstract Homeopathy can be used in dairy farming as a safe alternative to antibiotics, capable of reducing the expansion of microbial resistance, while maintaining the health of herds. However, homeopathic compounds can also be used as liver protectors, and can act in the modulation of liver function. Herbal homeopathic medicines can be used as hepatoprotective agents, since they have the ability to prevent and repair liver disorders that commonly affect lactating cows. Thus, knowledge of the therapeutic properties of plants allows the preparation of homeopathic preparations, capable of preserving the health of farm animals. Based on this, the aim of this review was to discuss plant compounds used in homeopathy as hepatoprotectors and their effects on liver metabolism and on the productive response of lactating ruminant animals.

Resumen La homeopatía se puede utilizar en la producción lechera como una alternativa segura a los antibióticos, capaz de reducir la expansión de la resistencia microbiana, manteniendo la salud de los rebaños. Sin embargo, los compuestos homeopáticos también pueden usarse como protectores del hígado y pueden actuar en la modulación de la función hepática. Los medicamentos homeopáticos a base de hierbas se pueden utilizar como agentes hepatoprotectores, ya que tienen la capacidad de prevenir y reparar los trastornos hepáticos que comúnmente afectan a las vacas lactantes. Así, el conocimiento de las propiedades terapéuticas de las plantas permite la elaboración de preparados homeopáticos, capaces de preservar la salud de los animales de granja. En base a esto, el objetivo de esta revisión es discutir los compuestos vegetales utilizados en homeopatía como hepatoprotectores y sus efectos sobre el metabolismo hepático y la respuesta productiva de los rumiantes lactantes.

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AIM: To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS: In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS: The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION: Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

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Introducción: la espirulina es un alga que se emplea como un suplemento alimenticio de gran importancia, consumido desde la antigüedad, actualmente son conocidas sus propiedades como hepatoprotector, antioxidante, anticancerígeno, entre otros, que brindan una mejor salud y por ende calidad de vida. Actualmente las enfermedades hepáticas y el cáncer tienen prevalencia convirtiéndose en un gran problema sanitario que aqueja a la humanidad. En este sentido el presente trabajo halla su importancia. Objetivo: realizar una revisión sobre la actividad farmacológica de las diferentes especies de espirulina relacionadas con el efecto hepatoprotector, antioxidante y anticancerígeno. Material y Métodos: se implementó una búsqueda exhaustiva en base de datos en línea como Pubmed, Scopus, Medline y Ebsco, se incluyeron solo trabajos originales completos de corte experimental y clínico publicados en el periodo 2000 a 2019. Desarrollo: se encontraron 2064 artículos relacionados de los cuales 58 cumplían los requisitos exigidos en el presente trabajo, fueron trabajados por análisis documental y agrupación en clusters atendiendo a sus propiedades farmacognósicas. Conclusiones: los artículos revisados refieren el gran potencial que tiene la espirulina como agente hepatoprotector, antiinflamatorio, antioxidante, citotóxico, antimutagénico, apoptótico y anticancerígeno soportado en su gran variedad de contenido nutracéutico(AU)

Introduction: Spirulina is an alga used as a food supplement of great importance that has been consumed since ancient times. At present, its hepatoprotective potential, antioxidant activity and anticancer effect among other properties are known. These properties provide better health and thus better quality of life. Currently, liver diseases and cancer have a significant prevalence, becoming a major health problem afflicting humankind. In this regard, the present work is particularly important. Objective: To review the pharmacological activity of different Spirulina species related to the hepatoprotective, antioxidant and anticancer effect. Material and methods: A rigorous search was carried out in online databases such as Pubmed, Scopus, Medline and EBSCO. Only complete original experimental and clinical works published from 2000 to 2019 were included. Development: A total of 2064 related articles were found. Of them, 58 fulfilled the requirements of the present work. Document analysis and cluster grouping were carried out taking into account its pharmacological properties. Conclusions: The reviewed articles provide information about the great potential of Spirulina as a hepatoprotective, anti-inflammatory, antioxidant, cytotoxic, antimutagenic, apoptotic and anticancer agent supported in its great variety of nutraceutical content(AU)

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BACKGROUND AND AIM: Although existing research confirms the antiparasitic effect of the Malacca plant against Plasmodium, its effect on the liver, one of the target organs of Plasmodium has not been investigated. Therefore, this study was conducted to explore the potential of the ethanolic extract of Malacca (Phyllanthus emblica) leaves in preventing liver damage in mice (Mus musculus) caused by Plasmodium berghei infection. MATERIALS AND METHODS: This study was conducted using the livers of 18 mice fixed in 10% neutral-buffered formalin. A completely randomized design with a unidirectional pattern comprising six treatments was used in this study, with each treatment consisting of three replications. Treatment 0 was the negative control group infected with P. berghei, treatment 1 was the positive control group infected with P. berghei followed by chloroquine administration at a dose of 5 mg/kg BW, and treatments 2, 3, 4, and 5 were groups infected with P. berghei and administered Malacca leaf ethanolic extracts at doses of 100, 300, 600, and 1200 mg/kg BW, respectively. The extracts were administered orally using a gastric tube for 4 consecutive days. Mice were sacrificed on the 7th day and livers were collected for histopathological examination. RESULTS: Histopathological examination of the livers of mice infected with P. berghei demonstrated the presence of hemosiderin, hydropic degeneration, fat degeneration, necrosis, and megalocytosis. However, all these histopathological changes were reduced in the livers of P. berghei-infected mice treated with various doses of Malacca leaf ethanolic extract. The differences between the treatments were found be statistically significant (p<0.05). CONCLUSION: Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with P. berghei. The dose of 600 mg/kg BW was found to be the most effective compared with the doses of 100, 300, and 1200 mg/kg BW.

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Fruit purees can be added to diet as alternative sources of bioactive compounds for the prevention and/or improvement of the complications of metabolic syndrome. In this work we evaluated the effect of the intake of low-fat diets enriched with fruit purees (guava-strawberry, guava-blackberry, guava-soursop, guava-passion fruit) on the body weight and biochemical markers in metabolic syndrome analogy (MSA)-induced rats. The rats (n=6 for each treatment) were induced with a high fat diet and were injected with streptozotocin, one dose every week for 4 consecutive weeks after fasting overnight, then healthy rats were fed with standard diet and MS rats were fed with standard diet plus each of the fruit puree, for 4 weeks. As novel findings, the diet enriched with fruit purees was associated with a reduction in body weight (~13-21 %) and a control in the metabolism of glucose by decreasing plasma glucose (~5963 %). Also, there was a reduction in the total cholesterol, triacylglycerols, low-density lipoproteins, and low enzymatic activities of alanine aminotransferase, alkaline phosphatase and γ-glutamyl transferase, useful metabolites in the control of inflammatory processes in the liver. A notable improvement in the liver morphology was observed indicating that the treatments had a hepatoprotective effect. The diet enriched with guava-blackberry puree caused the best results on most biochemical markers of MS rats. Therefore, diets enriched with fruit purees can be an alternative for MS individuals for the control and improvement of the complications caused by this syndrome.

Los purés de frutas se pueden agregar a la dieta como fuentes alternativas de compuestos bioactivos para la prevención y / o mejora de las complicaciones del síndrome metabólico. En este trabajo evaluamos el efecto de la ingesta de dietas bajas en grasas, enriquecidas con purés de frutas (guayaba-fresa, guayaba-mora, guayaba-guanábana, guayaba-maracuyá) sobre el peso corporal y los marcadores bioquímicos en el síndrome metabólico (SM) inducido en ratas. Las ratas (n = 6 para cada tratamiento) fueron inducidas con una dieta alta en grasas y se les inyectó estreptozotocina, una dosis cada semana durante 4 semanas consecutivas después de ayunar durante la noche. Luego, las ratas sanas fueron alimentadas con una dieta estándar; y las ratas con SM fueron alimentadas con dieta estándar más cada uno de los purés de frutas, durante 4 semanas. Como hallazgos novedosos, la dieta enriquecida con purés de frutas se asoció con una reducción en el peso corporal (~ 13-21 %) y un control en el metabolismo de la glucosa al disminuir la glucosa en plasma (~ 59-63 %). Además, hubo una reducción en el colesterol total, triacilgliceroles, lipoproteínas de baja densidad, y bajas actividades enzimáticas de alanina aminotransferasa, fosfatasa alcalina y gama-glutamil transferasa, metabolitos útiles en el control de los procesos inflamatorios en el hígado. Se observó una mejora notable en la morfología del hígado, lo que indica que los tratamientos tuvieron un efecto hepatoprotector. La dieta enriquecida con puré de guayaba y mora causó los mejores resultados en la mayoría de los marcadores bioquímicos de las ratas con SM. Por lo tanto, las dietas enriquecidas con purés de frutas pueden ser una alternativa para las personas con SM, para el control y la mejora de las complicaciones causadas por este síndrome.

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The active component in cullilawan oil can be synthesized into curcumin analogue product, which has pharmacological activity. The synthesis process by using conventional and microwave methods can produce different isomer products. Different synthesis products and models of animal are used to provide different hepatoprotective effects. The aim of this study was to use the curcumin analogue synthetic products (AKS-k and AKS-m) from cullilawan oil in male mice (Mus musculus L.) liver damage treatment induced by carbon tetrachloride (CCl4). The in vivo method was employed using biochemical of blood and histopathological images of liver cells as indicators. The results showed that the curcumin analogue synthetic product using microwave methods had better pharmacological effects than the conventional method product in terms of the results of blood biochemical analysis and microscopic images of liver cells.

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AIM: This research was conducted to obtain accurate information on the protective effects of Portulaca oleracea L. against hepatogastric diseases. RESULTS: P. oleracea L. (Purslane) has traditionally been used for the treatment of hepatogastric diseases. However, the low number of research studies has shown that P. oleracea L. possesses protective effects against hepatotoxic agents. The safety of P. oleracea L. has been demonstrated in several clinical trials. CONCLUSION: Modern pharmacological studies have indicated the gastroprotective and hepatoprotective effects of P. oleracea L. by using in vivo and in vitro models. However, due to lack of information of its effects in humans, more studies should be conducted to confirm the efficacy of P. oleracea L. in humans.

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Purpose: This research is devoted to designing the synthesis of sulfanyl-substituted 3,5-dimethylisoxazoles, which contain structural analogues of the SAM drug in the molecule. SAM (S-adenosyl-L-methionine), formed in the biosynthetic process, is used as an effective hepatoprotective drug. Complexation and hepatoprotective properties of the combinatorial series of bis(isoxazolylsulfanyl)ethane have been studied. Methods: Bis(isoxazol-4-ylmethylsulfanyl)alkanes were synthesized using the one-pot method. The structures of compounds were established by one-dimensional (1H,13C) and two-dimensional (COSY, HCQS, HMBC) NMR spectroscopy, mass-spectrometry and X-ray diffraction. The biological activity of the combinatorial series of sulfanyl derivatives of diketones, azoles and their metal complexes has been studied by in vivo method. Simulation of the animal associated processes was carried out in accordance with the principles of bioethics. Screening studies of hepatoprotective activity were carried out in a model of acute CC14 intoxication after a single injection intraperitoneally as a 50% solution in olive oil. The pharmacologically known hepatoprotective drug SAM served as a control. Results: Two-step synthesis of novel α,ω-bis(isoxazol-4-ylmethylsulfanyl)alkanes was carried out via the multicomponent reaction between 2,4-pentandione, CH2O and α,ω-dithiols, then the resulting α,ω-bis(1,3-diketone-2-ylmethylsulfanyl)alkanes were transformed by hydroxyl amine to obtain bis-isoxasole derivatives. Promising precursor 1,2-bis(isoxazol-4-ylmethylsulfanyl)ethane was converted to metal complexes by interaction with PdCl2 or CuCl. The obtained compounds were found to be practically non-toxic compounds (1001 - 3000 mg/kg) according to the classification of K.K. Sidorov, but copper complex refers to low-toxic compounds substances (165 mg/kg). Compounds of sulfanyl ethane series demonstrate hepatoprotective activity. Conclusion: Palladium(II) complex being almost non-toxic possesses hepatoprotective activity comparable to the drug like SAM.

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The pathological characteristic of cirrhosis is scarring which results in a structurally distorted and dysfunctional liver. Previously, we demonstrated that Col1a1 and Pparg genes are deregulated in CCl4 -induced cirrhosis but their normal expression levels are recovered upon treatment with IFC-305, an adenosine derivative. We observed that adenosine was able to modulate S-adenosylmethionine-dependent trans-methylation reactions, and recently, we found that IFC-305 modulates HDAC3 expression. Here, we investigated whether epigenetic mechanisms, involving DNA methylation processes and histone acetylation, could explain the re-establishment of gene expression mediated by IFC-305 in cirrhosis. Therefore, Wistar rats were CCl4 treated and a sub-group received IFC-305 to reverse fibrosis. Global changes in DNA methylation, 5-hydroxymethylation, and histone H4 acetylation were observed after treatment with IFC-305. In particular, during cirrhosis, the Pparg gene promoter is depleted of histone H4 acetylation, whereas IFC-305 administration restores normal histone acetylation levels which correlates with an increase of Pparg transcript and protein levels. In contrast, the promoter of Col1a1 gene is hypomethylated during cirrhosis but gains DNA methylation upon treatment with IFC-305 which correlates with a reduction of Col1a1 transcript and protein levels. Our results suggest a model in which cirrhosis results in a general loss of permissive chromatin histone marks which triggers the repression of the Pparg gene and the upregulation of the Col1a1 gene. Treatment with IFC-305 restores epigenetic modifications globally and specifically at the promoters of Pparg and Col1a1 genes. These results reveal one of the mechanisms of action of IFC-305 and suggest a possible therapeutic function in cirrhosis. J. Cell. Biochem. 119: 401-413, 2018. © 2017 Wiley Periodicals, Inc.

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BACKGROUND: Lead is one of the most toxic metals, producing severe organ damage in animals and humans. Oxidative stress is reported to play an important role in lead acetate-induced liver injury. AIM: This study was carried out to investigate the role of ethanol extract of Eucheuma cottonii in protecting against lead acetate-induced hepatotoxicity in male mice. MATERIALS AND METHODS: The sample used fifty male mice which were divided into five groups: negative control (mice were given daily with Aquadest); positive control (mice were given daily with lead acetate 20 mg/kg body weight (BW) orally once in a day for 21 days); and the treatment group (mice were given E. cottonii extracts 200 mg, 400 mg, and 800 mg/kg BW orally once in a day for 25 days, and on the 4th day, were given lead acetate 20 mg/kg BW 1 h after E. cottonii extract administration for 21 days). On day 25, the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured. The data of SGOT, SGPT, ALP, MDA, SOD, and GPx were analyzed with one-way ANOVA, followed by least significant difference test. RESULTS: The results showed that oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT, SGPT, ALP, and MDA levels. Moreover, there was a significant decrease in SOD and GPx levels. Treatment with E. cottonii extracts of 800 mg/kg BW but not with 200 mg/kg BW and 400 mg/kg BW significantly (P < 0.05) decreased the elevated SGPT, SGOT, ALP, and MDA levels as compared to positive control group. Treatment with E. cottonii extracts of 800 mg/kg BW also showed a significant increase in SOD and GPx levels as compared to positive control group. Treating mice with lead acetate showed different histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and fatty degeneration whereas animals treated with lead acetate and E. cottonii extracts showed an improvement in these changes and the tissue appeared with normal structures. CONCLUSION: It can be concluded that E. cottonii extracts could be a potent natural product and can provide a promising hepatoprotective effect against lead acetate-induced hepatotoxicity in mice. SUMMARY: In summary, Oxidative stress reported to play an important role in lead acetate induced liver injury. The lead acetate treatment significantly increased the SGOT, SGPT, ALP, MDA, and decreased the antioxidant enzymes (SOD and GPx) in liver. The inhibition of antioxidant enzymes will increase free radicals in liver tissues and might induce liver injury in mice. The presence of ethanol extract of Eucheuma cottonii with lead acetate showed protective effects as attenuating lead acetate against its liver toxicity, and this may be due to the activity of ethanol extract of Eucheuma cottonii as antioxidant. The antioxidant enzymes (SOD and GPx) were increased, and MDA, SGOT, SGPT, ALP were decreased after ethanol extract of Eucheuma cottonii administration. The enzymatic activities (SOD and GPx) and MDA in mice can be used as biomarkers of heavy metal toxicity such as lead acetate. Histopathological view of liver sections in the lead acetate treated group showed the liver damage, as compared to the negative control group. However, administration of ethanol extract of Eucheuma cottonii significantly improved the histopathological in liver of lead acetate-treated mice. From the results of this study we concluded that the ethanol extract of Eucheuma cottonii could be a potent natural product provide a promising protective effect against lead acetate induced liver toxicity in mice. Abbreviations Used: SGOT: Serum Glutamic Oxaloacetic Transaminase, SGPT: Serum Glutamic Pyruvate Transaminase, ALP: Alkaline Phosphatase, MDA: Malondialdehyde, SOD: Superoxide Dismutase, GPx: Glutathione Peroxidase.

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Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

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Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

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Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl4-induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl4 -induced liver damage in rats.

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