Effects of silybin supplementation on nutrient digestibility, hematological parameters, liver function indices, and liver-specific mi-RNA concentration in dogs.

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.

Liver Damage Produced by Malnutrition is Improved by Dietary Supplementation in Mice: Assessment of a Supplement Based on Buriti (A Cerrado Fruit) and Dairy By-products.

BACKGROUND: Malnutrition induced by dietary restriction produces several metabolic changes that affect body weight, the digestive system, and annex organs, including the liver. Malnutrition generates an inflammatory state and increases oxidative stress. The liver is one of the body vital organs, becoming necessary to analyze the impact of food supplementation on the repair of possible changes that may occur in this organ due to malnutrition. AIMS: To evaluate the effects of a low-cost supplementation derived from Buriti and dairy byproducts on liver recovery in malnourished mice, focusing on the expression of oxidative stressrelated genes, as well as biochemical and histological parameters. METHODS: Swiss mice were divided into six groups and submitted to two treatment phases: food restriction, for malnutrition onset; and renutrition, with mice being fed with different diets. RESULTS: Our results indicate that dietary supplementation was successful in recovering liver damage caused by malnutrition in animal models. The new supplement has been shown to recover liver damage with similar or superior results compared to the commercial reference supplement on the market. CONCLUSION: Our work presents a new composition of low cost food supplement based on buriti and dairy by-products, proven to be effective in the malnutrition treatment of malnutrition. The improvements were proven through the recovery of body weight, reduction of inflammation and oxidative stress.

Omega-3 derivatives, specialized pro-resolving mediators: Promising therapeutic tools for the treatment of pain in chronic liver disease.

The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury.

Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis.

BACKGROUND: Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes. AIM: To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis. METHODS: A literature search was conducted in PubMed and other sources, using the search terms "sarcopenia," "muscle," "malnutrition," "cirrhosis," "liver" and "frailty" from inception to April 2019, to identify the relevant studies and international guidelines. RESULTS: The prevalence of malnutrition/sarcopenia in cirrhosis is 23%-60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. CONCLUSIONS: Malnutrition/sarcopenia and frailty are unique, inter-related and multi-dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

Probiotics for Gastrointestinal and Liver Diseases: An Updated Review of the Published Literature.

BACKGROUND: Probiotics can be viewed as biological agents that modify the intestinal microbiota and certain cytokine profiles, which can lead to an improvement in certain gastrointestinal diseases, including diarrhea, inflammatory bowel disease, and liver disease. DISCUSSION: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. OBJECTIVE: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. METHODS/RESULTS: Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. CONCLUSION: While not efficacious in every disease process studied, probiotics have demonstrated some benefit in several specific gastrointestinal and liver diseases.

Nutrition in Pediatric Chronic Liver Disease.

More than one-half of children with chronic liver disease suffer from malnutrition, which leads not only to a poor quality of life and even possibly catastrophic complications, but also to poor outcomes after a liver transplantation. These children have increased metabolic demands but often decreased intake with malabsorption and altered nutrient utilization, all of which make it difficult to keep up with nutritional demands. Assessment of a patient's nutritional status should be timely, and it should be performed routinely and proactively. When specific nutritional needs are identified, these should be addressed with a multidisciplinary team approach and with the close guidance of an experienced pediatric dietician. The assessment includes anthropometric and laboratory assessments, in addition to a careful physical examination and a detailed patient history. The specific nutritional needs vary, but generally dietary intervention focuses on increasing caloric intake, supplementation with medium-chain triglycerides, and prevention of essential fatty acid and fat-soluble vitamin deficiencies. [Pediatr Ann. 2018;47(11):e445-e451.].

Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases.

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats.

Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML's effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague-Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats' morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer-binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1[Formula: see text] (IL-1[Formula: see text]) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage.

Nutritional Considerations for Dogs and Cats with Liver Disease.

The goals of nutritional management of liver disease in the dog and cat are directed at treating the clinical manifestations as opposed to treating the underlying cause. Specifically, the clinician strives to avoid overwhelming the remaining metabolic capacities of the damaged liver while providing sufficient nutrients for regeneration. A brief overview of liver diseases and associated clinical signs encountered in the dog and cat and a review of specific nutrients are discussed as well as amounts and sources of nutrients recommended to meet nutritional goals in the diseased liver.

When can nutritional therapy impact liver disease?

This article reviews the current literature regarding nutritional therapy in liver disease, with an emphasis on patients progressing to liver failure as well as surgical patients. Mechanisms of malnutrition and sarcopenia in liver failure patients as well as nutritional assessment, nutritional requirements of this patient population, and goals and methods of therapy are discussed. Additionally, recommendations for feeding, micronutrient, branched chain amino acid supplementation, and the use of pre- and probiotics are included. The impact of these methods can have on patients with advanced disease and those undergoing surgical procedures will be emphasized.

La dieta hiperproteica: su repercusión sobre albúmina sérica, líquido ascítico y estado nutricional en cirrosis / Hyperproteic diet: its impact on serum albumin, ascitic fluid and nutritional status in cirrhosis

Los pacientes con cirrosis hepática por cualquier etiología y muy especialmente alcohólica, presentan malnutrición proteico calórica, lo cual pudiera contribuir a la progresión de la enfermedad. El objetivo de esta investigación fue correlacionar el efecto del consumo de una dieta hiperproteica sobre los niveles de albúmina sérica y los niveles de albúmina del líquido ascítico con la ingesta dietética previa y posterior a la intervención nutricional en pacientes con cirrosis hepática; así como su repercusión sobre el estado nutricional. En este estudio prospectivo, experimental, longitudinal se evaluaron 10 pacientes con diagnóstico de cirrosis hepática, Child Pugh B, (8 hombres y 2 mujeres) (30 - 70 años). Se realizó evaluación antropométrica (IMC), bioquímica sérica y del líquido ascítico e indicadores dietéticos. El análisis se realizó mediante el programa SPSS 15 y Test de Wilcoxon (P=< 0,05). La albúmina sérica al inicio=3,6 + 1,3g/dl y 3,5 + 1,1gr/dl al final y la albúmina del líquido ascítico= 1,4 + 0,7g/dl antes y 2,5 + 0,8 g/dl después. En cuanto al estado nutricional al inicio 7 (70%)= normales, 1 (10 %) = desnutrición grado I y 2 (20%) obesidad. Al final: 6 pacientes (60%)= normales, 2 (20%) obesidad, 1 (10%) sobrepeso y 1 (10%) desnutrición grado I. La dieta hiperproteica contribuyó a aumentar los niveles de proteínas y albúmina del liquido ascítico, e igualmente influyó en el estado nutricional

The patients with cirrhosis for all etiology, have malnutrition and more risk of progression of the disease. The objective of this study was to correlate the effect of hyperproteic diet on levels of serum albumin and albumin levels in the ascitic fluid with dietary intake before and after nutritional intervention in patients with cirrhosis of the liver; as well as their impact on nutritional status. This prospective, experimental and longitudinal study assessed 10 patients with diagnosis of liver cirrhosis Child Pugh B, (8 men and 2 women) (30-70 years). Were practicated an anthropometric evaluation (BMI), serum biochemistry and the ascitic fluid and dietary indicators. The analysis was performed using the program SPSS 15 and Wilcoxon Test (P = < 0,05). Serum albumin at the beginning = 3. 6 + 1.3 g/dl and 3.5 + 1.1gr/dl albumin to the end of the liquid ascitic = 1.4 + 0. 7 g/dl before and 2.5 + 0.8 g/dl then. In terms of nutritional status at the beginning 7 (70%) = normal, 1 (10%) = malnutrition grade I and 2 (20%) obesity. At the end: 6 patients (60%) = normal, 2 (20%) obesity, overweight 1(10%) and 1 (10 per cent) malnutrition grade I. We concluded that hyperproteic diet contributed to increase protein and albumin levels from the ascitic fluid, and also influenced on the nutritional status

Compositional characterisation of soluble apple polysaccharides, and their antioxidant and hepatoprotective effects on acute CCl4-caused liver damage in mice.

Water-soluble apple peel polysaccharides (APP) and apple flesh polysaccharides (AFP) were isolated from Pink Lady fruits, and their in vitro antioxidant capacities were characterised by DPPH(), HO(), and O(2)(-) systems, and ferric-reducing antioxidant power assay. Oral administration of APP at 250 and 500 mg/kg bw in mice was shown to be as effective as AFP in lowering the CCl(4)-caused increases of serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities, and hepatic malondialdehyde level, and antagonising the decreases in antioxidant superoxide dismutase and glutathione peroxidase activities caused by CCl(4) (p<0.05). Histopathological examinations further confirmed that both APP and AFP could protect the liver from CCl(4)-induced histological alteration. HPLC analysis also showed similar profiles of monosaccharide composition for APP and AFP with arabinose, galactose and galacturonic acid being main component monosaccharides. All of these findings demonstrate that the extracts of both APP and AFP possess antioxidant and hepatoprotective potential.

Dietary L-arginine supplementation alleviates liver injury caused by Escherichia coli LPS in weaned pigs.

This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate Escherichia coli LPS-induced liver injury through the TLR4 signaling pathway in weaned pigs. Eighteen weaned pigs were allotted to three treatments: non-challenged control, LPS challenged control and LPS + 0.5% Arg. On d 18, pigs were injected with LPS at 100 µg/kg of body weight (BW) or sterile saline. Blood samples were obtained at 4 h post-injection. Pigs were then sacrificed for the collection of liver samples. Arg supplementation (0.5%) alleviated liver morphological impairment, including hepatocyte caryolysis, karyopycnosis and fibroblast proliferation induced by LPS challenge; it mitigated the increase of serum aspartate aminotransferase and alkaline phosphatase activities induced by LPS (P < 0.05); it prevented the increase of hepatic TNF-α, malondialdehyde contents and mast cell number induced by LPS administration (P < 0.05); and it attenuated the elevation of hepatic NF-κB and TLR4-positive cell percentages (P < 0.05). These results indicate that Arg supplementation has beneficial effects in attenuating hepatic morphological and functional injury induced by LPS challenge in piglets. Additionally, it is possible that the protective effects of Arg on the liver are associated with a decreased release of liver pro-inflammatory cytokines and free radicals through inhibiting TLR4 signaling.

Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with short-bowel syndrome.

STUDY OBJECTIVE: To evaluate the use of enteral fish oil for the treatment of parenteral nutrition-associated liver disease (PNALD). DESIGN: Retrospective case series. SETTING: Pediatric academic hospital and outpatient clinic. PATIENTS: Six parenteral nutrition-dependent infants with short-bowel syndrome and PNALD. MEASUREMENTS AND MAIN RESULTS: The six infants received supplementation with enteral fish oil, and treatment was evaluated over a 12-week period. The PNALD, as reflected by elevated total bilirubin levels, completely reversed in four of the six infants within a mean ± SD of 5 ± 2.6 weeks (range 2-8 wks) after initiation of the enteral fish oil supplementation. In addition, improvement in enteral feedings occurred after starting enteral fish oil therapy. CONCLUSION: Enteral fish oil may be an effective adjunctive treatment option for infants with PNALD, particularly for those infants with PNALD who are tolerating some amount of enteral nutrition as the result of an adequate amount of small bowel.

Nutrition in hepatic encephalopathy.

Protein calorie malnutrition (PCM) is a well-known complication of chronic liver disease (CLD). A major contribution to PCM in CLD is restriction of dietary protein intake. After many decades of injudicious reduction in dietary protein, cirrhotic patients are now prescribed appropriate amounts of protein. PCM in CLD is known to be associated with life-threatening complications. In the general approach to these patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Most patients tolerate a normal amount of dietary protein without developing hepatic encephalopathy (HE). Oral branched-chain amino acids (BCAAs) have a limited role in HE. Patients who exhibit dietary protein intolerance originally were thought to be best treated with BCAA formulations. Mixed evidence has been reported in multiple studies. In keeping with other reports, this article shows that in animal protein-intolerant patients, even those with advanced cirrhosis, vegetable protein-based diets are well tolerated. Another approach to management of apparent dietary intolerance is to optimize HE treatment with available medications. This article reviews the causes of HE, minimal HE, and PCM; examines nutrition requirements and assessment; and discusses treatment options for malnutrition in HE.

Hepatoprotective and curative properties of Kombucha tea against carbon tetrachloride-induced toxicity.

Kombucha tea (KT) is sugared black tea fermented with a symbiotic culture of acetic acid bacteria and yeasts, which is said to be tea fungus. KT is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature. In the present study, KT along with black tea (BT) and black tea manufactured with tea fungus enzymes (enzyme-processed tea, ET) was evaluated for hepatoprotective and curative properties against CCl4-induced toxicity, using male albino rats as an experimental model by analyzing aspartate transaminase, alanine transaminase, and alkaline phosphatase in plasma and malondialdehyde content in plasma and liver tissues. Histopathological analysis of liver tissue was also included. Results showed that BT, ET, and KT have the potential to revert the CCl4-induced hepatotoxicity. Among the three types of teas tried, KT was found to be more efficient than BT and ET. Antioxidant molecules produced during the fermentation period could be the reason for the efficient hepatoprotective and curative properties of KT against CCI4-induced hepatotoxicity.

Localization of polypyrimidine-tract-binding protein is involved in the regulation of albumin synthesis by branched-chain amino acids in HepG2 cells.

Long-term supplementation of branched-chain amino acids (BCAA) improves hypoalbuminemia in patients with cirrhosis. Our previous findings have suggested that the binding of polypyrimidine-tract-binding protein (PTB) to rat albumin mRNA attenuates its translation. The aim of the present study was to investigate the role of PTB in the regulation of albumin synthesis by BCAA in human hepatoma cells. HepG2 cells were cultured in a medium containing no amino acids (AA-free medium), a medium containing only 1 amino acid (a BCAA: valine, leucine or isoleucine) or a medium containing all 20 amino acids (AA-complete medium). HepG2 cells cultured in AA-complete medium secreted much more albumin than cells cultured in AA-free medium, with no difference in albumin mRNA levels. In cells cultured in AA-free medium, nuclear export of PTB was observed, and the level of the albumin mRNA-PTB complex was greater than in cells cultured in AA-complete medium. Addition of amino acids stimulated nuclear import of PTB. However, addition of amino acids with rapamycin inhibited the nuclear import of PTB. The addition of leucine, but not of valine or isoleucine, to AA-free medium increased albumin secretion and stimulated the nuclear import of PTB. These data indicate that the mammalian target of rapamycin is involved in the regulation of PTB localization and that leucine promotes albumin synthesis by inhibiting the formation of the albumin mRNA-PTB complex.

[Bioactive substance used for treatment and preventive maintenance of liver diseases].

In the present article the review of bioactive substances rendering beneficial effect on an organism at diseases of a liver is resulted. Action of such classes of bioactive substances as amino acids and their derivatives, vitamins, macro- and microelements, herbal bioactive substances, cytamins is described. Bioactive substances can be used in manufacture food supplements or foodstuffs of a medical and prophylactic feed.