Choosing Appropriate Nutritional Therapy for Patients With Anorexia Nervosa Exhibiting Liver Dysfunction: A Case Report.

Anorexia nervosa (AN) presents with a variety of physical complications such as hypoglycemia, electrolyte abnormalities, and dehydration associated with starvation, requiring rapid weight gain through nutritional therapy. However, despite nutritional therapy, patients are at risk of many serious medical complications, including hypoglycemia, hypophosphatemia, edema, and liver damage. Starvation has been found to cause hepatocyte injury with mild-to-severe increases in liver enzyme levels, and distinguishing between autophagy and refeeding syndrome is important for treatment strategies. Herein, we report a rare case of sudden liver injury after the initiation of nutritional therapy in a patient with AN. A 35-year-old woman was admitted to our hospital for the treatment of weight loss due to AN. Nutritional therapy was initiated at 600 kcal/day and increased to 1500 kcal/day on the 21st day of admission. On the 22nd day after admission, rapid liver injury was observed, with an aspartate aminotransferase level of 141 U/L and an alanine aminotransferase level of 221 U/L. After the exclusion of refeeding syndrome, since there was no evidence of hypokalemia, hypophosphatemia, or fatty liver disease based on blood tests and abdominal echography, we diagnosed starvation-induced hepatocyte autophagy, and she was treated with the same calories. Her liver dysfunction gradually improved thereafter. This case report highlights the clinical utility of identifying the etiology of hepatic dysfunction in patients with AN. Clinicians must make appropriate decisions regarding continuing or reducing nutritional therapy based on relevant tests when patients with AN develop liver dysfunction after the initiation of nutritional therapy.

Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children.

BACKGROUND AND PURPOSE: Iron overload in the body is associated with serious and irreversible tissue damage. This study aimed to investigate the iron-chelating, antioxidant, anti-inflammatory, and hepatoprotective activities of grape seed extract (GSE) supplement as well as its safety in ß-thalassemia major (ß-TM) pediatric patients receiving deferasirox as a standard iron-chelation therapy. MATERIALS AND METHODS: The children were randomly allocated to either GSE group (n = 30) or control group (n = 30) to receive GSE (100 mg/day) or placebo capsules, respectively, for 4 weeks. The serum levels of iron, ferritin, total iron-binding capacity (TIBC), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and glutathione (GSH) as well as superoxide dismutase (SOD) activity and hemoglobin (Hb) concentration were measured pre-and post-intervention. RESULTS: GSE supplement significantly attenuated the serum levels of iron (p = 0.030), ferritin (p = 0.017), ALT (p = 0.000), AST (p = 0.000), TNF-α (p = 0.000), and hs-CRP (p = 0.001). The TIBC level (p = 0.020) significantly enhanced in the GSE group compared with the placebo group. Moreover, GSE supplement remarkably improved the oxidative stress markers, MDA (p = 0.000) and GSH (p = 0.001). The changes in the SOD activity (p = 0.590) and Hb concentration (p = 0.670) were not statistically different between the groups. CONCLUSION: GSE supplement possesses several health beneficial influences on children with ß-TM by alleviating iron burden, oxidative stress, inflammation, and liver dysfunction.

Severe Drug-Induced Liver Injury From Over-the-Counter Medication.

Drug-induced liver injury (DILI) is difficult to diagnose as it presents with a wide variety of clinical manifestations and there is no established specific biomarker. However, clinicians require expertise in diagnosing DILI as it can lead to critical illness, is relatively common, and can be caused by a variety of drugs, herbal medicines, and supplements. A 67-year-old male was admitted to the hospital with a fever, jaundice, and fatigue. Abdominal ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no morphological abnormalities in the hepatobiliary system. On the third day of hospitalization, the liver damage and acute kidney injury progressed, and the patient was transferred to our intensive care unit. To further investigate the cause of multiple organ damage, the patient underwent repeated history taking and additional laboratory testing. In addition to the common causes of hepatic and renal damage, we also tested for rickettsiosis and leptospirosis, as the patient reported partaking regularly in outdoor leisure activities. On day seven of hospitalization, the patient recalled taking over-the-counter herbal flu medications approximately five days prior to admission; therefore, we suspected DILI and performed a drug-induced lymphocyte stimulation test (DLST). The DLST was positive for one drug. As other causes had been ruled out, the patient was diagnosed with severe DILI. The clinical course of the patient was observed with the patient's laboratory data and fever improving spontaneously. This case taught us several important lessons for the investigation of liver injury. Firstly, even with over-the-counter drugs, liver injury can be severe. Secondly, while the DLST is available for investigating DILI, false positives, especially for medicinal herbs, should be noted, and it is necessary to adequately rule out other diseases. Finally, when the cause of liver injury is unclear, patient history taking should be repeated carefully.

Vitamin D Status and Potential Therapeutic Options in Critically Ill Patients: A Narrative Review of the Clinical Evidence.

Vitamin D covers roles of paramount importance in the regulation of multiple physiological pathways of the organism. The metabolism of vitamin D involves kidney-liver crosstalk and requires an adequate function of these organs, where vitamin D is progressively turned into active forms. Vitamin D deficiency has been widely reported in patients living in the community, being prevalent among the most vulnerable subjects. It has been also documented in many critically ill patients upon admission to the intensive care unit. In this context, vitamin D deficiency may represent a risk factor for the development of life-threatening clinical conditions (e.g., infection and sepsis) and worse clinical outcomes. Several researchers have investigated the impact of vitamin D supplementation showing its feasibility, safety, and effectiveness, although conflicting results have put into question its real benefit in critically ill patients. The existing studies included heterogeneous critically ill populations and used slightly different protocols of vitamin D supplementation. For these reasons, pooling up the results is difficult and not conclusive. In this narrative review, we described vitamin D physiology and the pathophysiology of vitamin D depletion with a specific focus on critically ill patients with liver dysfunction, acute kidney injury, acute respiratory failure, and sepsis.

Prim-O-glucosycimifugin attenuates liver injury in septic mice by inhibiting NLRP3 inflammasome/caspase-1 signaling cascades in macrophages.

BACKGROUND: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear. PURPOSE: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway. METHOD: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1ß and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1ß and IL-18 were measured by ELISA assays. RESULTS: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1ß and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950. CONCLUSION: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate.

Infused aqueous curry tea extracts ameliorate Nω -Nitro-L-Arginine Methyl Ester-induced liver dysfunction in male albino Wistar rats.

BACKGROUND: Murraya koenigii (L.) Spreng. (Rutaceae) has been reported to positively affect liver function. However, the effect of M. koenigii leaves on Nω -Nitro-L-Arginine Methyl Ester (L-NAME) induced liver dysfunction is unknown. The aim of the present study was therefore to investigate the effect of M.koenigii leaves as tea on L-NAME induced liver dysfunction. METHODS: Two variants of curry tea were formulated; one was formulated entirely from leaves of M. koenigii, the other was formulated with thaumatin-rich aril obtained from seeds of Thaumatococcus danielii (Benn.) Benth. (Marantaceae). Group I animals served as control and were untreated. Groups II and V animals were administered curry tea (CT). Group III and VI animals received curry-thaumatin tea (CTT). Concurrently, L-NAME (40 mg/kg) was administered to groups IV-VI respectively for 21 days. Blood and liver samples were collected at the end of the study for biochemical, histological, and immunohistochemical analysis. RESULTS: L-NAME induced liver dysfunction evidenced by liver histology, increased activities of ALT, AST, hyperlipidemia, hepatic oxidative stress and increased hepatic NF-kB expression. Administration of CT and CTT ameliorated the L-NAME induced liver dysfunction evidenced by liver histology, increased NO hepatic bioavailability, reduced activity of ALT and AST, increased hepatic antioxidant system and decreased hepatic NF-kB expression. Thaumatin taste/flavor enhancer did not significantly reduce or potentiate the hepatoprotective, antioxidant and anti-lipidemic property of aqueous curry tea extracts in rats. CONCLUSION: L-NAME impaired liver function in rats. CT and CTT interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction. PRACTICAL APPLICATIONS: The study reports that non-selective inhibition of nitric oxide by L-NAME in rats impairs liver function and formulated curry tea types interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction in rats.

COVID-19 and liver dysfunction: What nutritionists need to know.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

Preparation and Evaluation of Possible Antioxidant Activities of Rose Traditional Tablet"(Qurs-e-Vard)" A Selected Traditional Persian Medicine (TPM) Formulation via Various Procedures.

BACKGROUND: Free radicals can lead to liver dysfunction. Quality control of traditional formulations ensures their safe, pure, and pharmaceutical efficacy. "Qurs-e-Vard", containing petals of Rosa damascena Mill., fruits of Rhus coriaria L. and roots of Glycyrrhiza glabra L. has been suggested as a hepatoprotective preparation in Traditional Persian Medicine (TPM). OBJECTIVE: This study was directed at the evaluation of the phytochemical characterization, standardization, and in vitro antioxidant activity determination of a solid formulation and its components. METHODS: Some qualitative and quantitative controls were performed like ash value, heavy metals investigation, and microbial contamination. The phytochemical assays were used for obtaining total phenolic and flavonoid contents with spectrophotometric methods. 2, 2-Diphenyl-1-c (DPPH) and Nitric Oxide (NO) assays were run for determining Radical scavenging activities of the formulation and its components. Ferric reducing antioxidant power assay (FRAP) was determined as well. RESULTS: Total phenolic contents of hydroalcoholic and aqueous extracts of the polyherbal formulation measured respectively, (376±0.93) and (297.6±0.96) mg of gallic acid/g of dry matter. Total flavonoid contents of the formulation were also measured (36.27±0.98) for hydroalcoholic extract and (17.79±0.86) mg of quercetin/g of dry matter for aqueous extract. The IC50 of hydroalcoholic and aqueous extract was obtained (88.14±1.15) and (140.78±2.98) µg/ml, respectively. NO scavenging percentages (200µg/ml) of hydroalcoholic and aqueous extracts were measured (59.11±2.15) and (65.08±2.35). FRAP values of hydroalcoholic and aqueous extracts were achieved (255.24±3.45) and (134.57±3.45) µg/ml as well. CONCLUSION: Our findings indicated that this polyherbal formulation and its components have justifiable antioxidant effects.

Decaisnea insignis Seed Oil Inhibits Trimethylamine-N-oxide Formation and Remodels Intestinal Microbiota to Alleviate Liver Dysfunction in l-Carnitine Feeding Mice.

Elevated circulating level of the intestinal microbiota-derived l-carnitine metabolite trimethylamine-N-oxide (TMAO) has recently been linked to many chronic diseases. The purpose of our study was to investigate the effects of omega-7-enriched Decaisnea insignis seed oil (DISO) on reducing TMAO formation to prevent the l-carnitine-induced hepatic damage in mice. Feeding of mice with 3% l-carnitine in drinking water clearly increased the serum and urinary levels of TMAO (p < 0.05 vs Normal), whereas the serum and urinary TMAO formation was sharply reduced by DISO administration (p < 0.05). Meanwhile, DISO resulted in strong inhibition against the elevation of hepatic injury marker (AST, ALT, and ALP) activities and dyslipidemia (TC, TG, LDL-C, and HDL-C), as well as liver inflammatory cytokine (IL-1, IL-6, TNF-α, and TNF-ß) release in l-carnitine-fed mice (p < 0.05). As revealed by 16S rDNA gene sequencing, DISO significantly inhibited the l-carnitine-induced elevations in the abundance of Firmicutes, Proteobacteria, and Erysipelotrichaceae and the increases in the proportion of Lactobacillus and Akkermansia, revealing that DISO attenuated the l-carnitine-caused gut dysbiosis. These findings suggested that DISO could alleviate liver dysfunction in l-carnitine-fed mice, which might be due to the protection against TMAO formation by modulating the gut microbiota.

Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey.

BACKGROUND: Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose-effect on AEs. METHODS: A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. RESULTS: Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose-effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. CONCLUSIONS: IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

Osteopathic Physical Exam Findings in Chronic Hepatitis C: A Case Study.

Greater than two-thirds of all Hepatitis C virus (HCV) infections are chronic, leading to extrahepatic changes in the body. The objective of this article was to describe various musculoskeletal findings that can be elicited during an osteopathic structural exam in the setting of liver dysfunction along with an overview of hepatic viscerosomatics and Chapman's points. Osteopathic medicine is a branch of modern medicine that utilizes hands-on diagnosis and treatment through musculoskeletal manifestations in addition to the standard allopathic practices. Herein, we presented a case of untreated chronic HCV infection, complicated by polysubstance abuse, with positive findings on osteopathic physical exam consistent with hepatic pathology.

Transdermal fennel essential oil nanoemulsions with promising hepatic dysfunction healing effect: in vitro and in vivo study.

Fennel (Foeniculum vulgare Mill.) is a member of family Apiaceae. Trans-anethole, the major component of Fennel essential oil (FEO), possesses antioxidant and hepatoprotective effects. Transdermal nanoemulsions (NEs) are advanced colloidal systems for systemic and controlled drug delivery through the stratum corneum barrier. FEO NEs were prepared using the oil Lauroglycol™ 90, as it provides a larger NE existence zone than Captex® 300, in the constructed phase diagrams. Six systems were prepared using Tween20/propylene glycol (S/CoS) in the ratios 2:1 and 3:1 with oil to S/CoS mass ratios 1:9, 2:8 and 3:7. Physicochemical characterization revealed optimum properties regarding thermodynamic stability, droplet size and pH with a Newtonian flow pattern. In vitro permeation study in rat skin revealed the highest cumulative amount permeated (µg/cm2), flux and permeability coefficient values for F4 made up of 2% FEO, 4.67% Lauroglycol™ 90, 60% S/CoS in the ratio 3:1. Results of the in vivo hepatic dysfunction study in rats indicate promising significant amelioration of liver function reflected in ALT, AST, ALP, bilirubin, albumin, malondialdehyde and ammonia plasma levels. The results signify the promising approach of FEO NEs in achieving remedy of liver toxicity. The most promising effect is inherent to F4 which imparts a more positive effect than FEO.

[Noble Heart Failure Therapy Using Food Compositions].

　Hemodynamic stresses, including hypertension and myocardial infarction, activate neurohumoral factors such as the sympathetic nervous system and the renin-angiotensin system, and can lead to the progression of heart failure. Established pharmacological agents such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and ß-blockers target extra-cellular molecules and receptors on the cell membrane. These agents have shown some efficacy for the treatment of heart failure, but the long-term survival rate of patients with heart failure remains low. Additional effective pharmacological approaches are urgently required. Our previous studies have demonstrated that curcumin, a natural polyphenol derived from the root of Curcuma longa, prevented the development of heart failure in rat models of myocardial infarction and hypertensive heart disease. However, until recently curcumin's poor water solubility and extremely low bioavailability have presented serious challenges to its clinical applicability. In recent years, highly absorbable curcumin preparations have been developed using methods such as nanoparticle formation and micellization, and there are now high expectations for their wide clinical application. Our group has developed a highly absorbable curcumin formulation called Theracurmin using nanoparticulation and surface processing techniques. Our preliminary data indicated that Theracurmin may improve left ventricular diastolic function. Furthermore, we have already completed and are currently carrying out several clinical trials using Theracurmin against heart failure-related diseases. This paper summarizes and discusses the potential clinical applications of curcumin, focusing on our highly absorbable curcumin formulation, Theracurmin.

Aerobic training and L-arginine supplement attenuates myocardial infarction-induced kidney and liver injury in rats via reduced oxidative stress.

INTRODUCTION: The aim of the present study was to determine the effect of exercise training and l-arginine supplementation on kidney and liver injury in rats with myocardial infarction (MI). MATERIAL AND METHODS: Four weeks after MI, 50 male wistar rats randomly divided into five followed groups: sham surgery without MI (Sham, n=10), Sedentary-MI (Sed-MI, n=10) 3: L-Arginine-MI (La-MI, n=10) 4: Exercise training-MI (Ex-MI, n=10) and 5: Exercise and L-arginine-MI (Ex+La-MI). Ex-MI and Ex+La-MI groups running on a treadmill for 10 weeks with moderate intensity. Rats in the L-arginine-treated groups drank water containing 4% L-arginine. Tissues oxidative stress and kidney and liver functional indices were measured after treatments. RESULT: Urea as a kidney function indexes, increased in Sed-MI group in compared to sham group and decreased significantly in Ex-MI and Ex+La-MI groups. The level of catalase (CAT) and glutathione stimulating hormone (GSH) of kidney were significantly lower in the MI-groups compared with the Sham group and kidney Malondialdehyde (MDA) levels increased after MI and significantly decreased in response to aerobic training and L-arginine. As well as, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as liver injury indices, increased in MI-groups and decreased by training and L-arginine. In this regards, liver MDA and CAT respectively increased and decreased in MI-groups, but aerobic training and L-arginine increased liver glutathione per-oxidase (GPx) and decreased liver MDA. CONCLUSION: These results demonstrated that kidney and liver function impaired 14 weeks after MI and aerobic training and L-arginine supplementation synergistically ameliorated kidneys and liver injury in myocardial infarction rats through oxidative stress reduction.

Hepatoprotective Effect of Essential Oils from Hyptis crenata in Sepsis-Induced Liver Dysfunction.

No specific therapeutics are available for the treatment of sepsis-induced liver dysfunction, a clinical complication strongly associated with the high mortality rate of septic patients. This study investigated the effect of the essential oil of Hyptis crenata (EOHc), a lamiaceae plant used to treat liver disturbances in Brazilian folk medicine, on liver function during early sepsis. Sepsis was induced by the cecal ligation and puncture (CLP) model. Rats were divided into four groups: Sham, Sham+EOHc, CLP, and CLP+EOHc. EOHc (300 mg/kg) was orally administered 12 and 24 h after surgery. The animals were sacrificed for blood collection and liver tissue samples 48 h after surgery. Hepatic function was evaluated by measuring serum bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase, and alanine aminotransferase (ALT) levels. The levels of malondialdehyde and the activity of superoxide dismutase, catalase, and GSH peroxidase (GSH-Px) were measured for assessment of oxidative stress. Liver morphology was analyzed by hematoxylin and eosin staining. EOHc normalized serum ALP, ALT, and bilirubin levels and inhibited morphological changes. In addition, we observed that EOHc inhibited elevation in hepatic lipid peroxidation and reduction of the glutathione peroxidase activity induced by sepsis. Our data show that EOHc plays a protective effect against liver injury induced by sepsis.

N-Acetyl-l-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats.

AIM: Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not. METHODOLOGY: We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity -LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat). KEY FINDINGS: Chronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels. SIGNIFICANCE: Our study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS.

Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann-Pick-Disease Type C1.

Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study an additive hepatoprotective effect of a combination of 2-hydroxypropyl-ß-cyclodextrin (HPßCD), miglustat and allopregnanolone (combination therapy) with the previously established monotherapy using HPßCD. We examined transgene effects as well as treatment effects on liver morphology and hepatic lipid metabolism, focusing on hepatic cholesterol transporter genes. Livers of Npc1-/- mice showed hepatic cholesterol sequestration with consecutive liver injury, an increase of lipogenetic gene expression, e.g., HMG-CoA, a decrease of lipolytic gene expression, e.g., pparα and acox1, and a decrease of lipid transporter gene expression, e.g., acat1, abca1 and fatp2. Both, combination therapy and monotherapy, led to a reduction of hepatic lipids and an amelioration of NPC1 liver disease symptoms. Monotherapy effects were related to pparα- and acox1-associated lipolysis/ß-oxidation and to fatp2-induced fatty acid transport, whereas the combination therapy additionally increased the cholesterol transport via abca1 and apoE. However, HPßCD monotherapy additionally increased cholesterol synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA expression, probably as a result of increased hepatocellular proliferation.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation.

BACKGROUND: Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. METHODS: To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. RESULTS: Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. CONCLUSION: These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction.

GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS.

BACKGROUND: This study aims to examine the protective effect of green tea on the disturbances in oxidative stress and apoptosis related factors, mostly produced due to perinatal lipopolysaccharide (LPS) exposure, that subsequently induces liver cell damage. MATERIALS AND METHODS: Anti-free radical, Antioxidant, scavenging, geno-protective, and antiapoptotic activity of aqueous green tea extract (AGTE) were assessed against LPS-induced hepatic dysfunction in newborn-rats. AGTE at doses of 100 & 200 mg/kg was orally administered daily to rat dams, during gestation and lactation. RESULTS: AGTE was observed to exhibit protective effects by significantly attenuating LPS-induced alterations in serum AST, ALT, bilirubin, and albumin levels. Significant increase in the total antioxidant capacity (TAC), DNA contents, and reduction in nitric oxide (NO) levels were observed in AGTE treated rats comparing LPS-toxicated ones. Additionally, AGTE treatment significantly down-regulated apoptotic markers and this effect was directly correlated to the degree of hepatic fibrosis. The possible mechanisms of the potential therapeutic-liver protective effect of AGTE could be due to free radical scavenging potential and antiapoptotic properties caused by the presence of antioxidant polyphenolic components in AGTE. CONCLUSION: We thereby propose, based on our findings, that the anti-free radical and anti-apoptotic inducing properties of AGTE active constituents attribute to its functional efficacy as anti-fibrotic agent.

GC-MS analysis and hepatoprotective activity of the n-hexane extract of Acrocarpus fraxinifolius leaves against paracetamol-induced hepatotoxicity in male albino rats.

CONTEXT: In Egypt, the burden of liver diseases is exceptionally high. OBJECTIVE: To investigate the components of the n-hexane extract of Acrocarpus fraxinifolius Arn. (Leguminosae) and its hepatoprotective activity against paracetamol (APAP)-induced hepatotoxicity in rats. MATERIAL AND METHODS: TRACE GC ultra gas chromatogaphic spectrometry was used for extract analysis. Thirty albino rats were divided into six groups (five rats in each). Group 1 was the healthy control; Groups 2 and 3 were healthy treated groups (250 and 500 mg/kg b.w. of the extract, respectively) for seven days. Group 4 was hepatotoxicity control (APAP intoxicated group). Groups 5 and 6 received APAP + extract 250 and APAP + extract 500, respectively. RESULTS: Chromatographic analysis revealed the presence of 36 components. Major compounds were α-tocopherol (18.23%), labda-8 (20)-13-dien-15-oic acid (13.15%), lupeol (11.93%), phytol (10.95%) and squalene (7.19%). In the acute oral toxicity study, the mortality rates and behavioural signs of toxicity were zero in all groups (doses from 0 to 5 g/kg b.w. of A. fraxinifolius). LD50 was found to be greater than 5 g/kg of the extract. Only the high dose (500 mg/kg b.w.) of extract significantly alleviated the liver relative weight (4.01 ± 0.06) and biomarkers, as serum aspartate aminotransferase (62.87 ± 1.41), alanine aminotransferase (46.74 ± 1.45), alkaline phosphatase (65.96 ± 0.74), lipid profiles (180.39 ± 3.51), bilirubin profiles (2.30 ± 0.06) and hepatic lipid peroxidation (114.20 ± 2.06), and increased body weight (11.58 ± 0.20), serum protein profile (11.09 ± 0.46) and hepatic total antioxidant capacity (23.78 ± 0.66) in APAP-induced hepatotoxicity in rats. CONCLUSION: Our study proves the antihepatotoxic/antioxidant efficacies of A. fraxinifolius hexane extract.