Polyene Phosphatidylcholine Research Articles

Pharmacotherapies for Drug-Induced Liver Injury: A Current Literature Review.

Drug-induced liver injury (DILI) has become a serious public health problem. For the management of DILI, discontinuation of suspicious drug or medicine is the first step, but the treatments including drugs and supporting approaches are needed. Reference to clinical patterns and disease severity grades of DILI, the treatment drugs were considered to summarize into hepatoprotective drugs (N-acetylcysteine and Glutathione, Glycyrrhizin acid preparation, Polyene phosphatidylcholine, Bicyclol, Silymarin), anticholestatic drug (Ursodeoxycholic acid, S-adenosylmethionine, Cholestyramine), immunosuppressants (Glucocorticoids) and specific treatment agents (L-carnitine, Anticoagulants). The current article reviewed the accumulated literature with evidence-based medicine researches for DILI in clinical practice. Also the drawbacks of the clinical studies involved in the article, unmet needs and prospective development for DILI therapy were discussed.

Lipidomic-based investigation into the therapeutic effects of polyene phosphatidylcholine and Babao Dan on rats with non-alcoholic fatty liver disease.

In recent years, with the improvement of people's living standards, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. In this paper, the metabolic disorders in Sprague Dawley (SD) rats were induced by a choline-deficient, l-amino acid-defined (CDAA) diet. The therapeutic effects of polyene phosphatidylcholine (PPC) and Babao Dan (BBD) on NAFLD were observed. Lipidomic analysis was performed using ultra-high-performance liquid chromatography-Orbitrap MS, and data analysis and lipid identification were performed using the software LipidSearch. Both PPC and BBD can reduce lipid accumulation in the liver and improve abnormal biochemical indicators in rats, including reduction of triglycerides, total cholesterol, alanine transaminase and aspartate transaminase in serum. In addition, lipids in rat serum were systematically analyzed by lipidomics. The lipidomic results showed that the most obvious lipids with abnormal metabolism in CDAA diet-induced rats were glycerides (triglycerides and diacylglycerols), phospholipids and cholesterol esters. Both BBD and PPC partly reversed the disturbance to lipids induced by the CDAA diet. PPC may be more effective than BBD in alleviating NAFLD because it has a better effect on inhibiting the abnormal accumulation of lipids and reducing the inflammatory reaction in the body.

S2694 Severe Acute Liver Failure in a Patient With SARS-CoV-2 Infection

Introduction: Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, are regularly found to have elevated LFTs. Up to 46% had elevated AST and 35% had elevated ALT. Occasional elevations in GGT, ALP, and total bilirubin are also seen. These elevations were usually below 5 times the upper limit of normal (ULN). Less than 10% of patients had severe liver injury (ALT > 5 times ULN). Hepatic injury in COVID-19 can be attributed to numerous causes including direct injury, drug toxicity and inflammatory storm. Direct injury is thought to occur when SARS-CoV-2 binds directly to ACE-2 which are abundantly expressed in biliary and liver epithelial cells. We present the case of an 88-year-old COVID-19 patient with severe liver failure managed conservatively. Case Description/Methods: 88-year-old male with history of CHF, atrial fibrillation on Apixaban, DM-2, HTN and recent diagnosis of COVID-19 presented with shortness of breath. Vitally, he was normotensive but hypoxic. Initial labs are shown in Table 1. He denied an established history of liver disease, alcohol use or hepatotoxic drug use. Chest CTA had findings concerning for COVID-19 pneumonia and acute pulmonary embolism. He was not started on Remdesivir due to elevated LFTs. His acute hepatitis panel and acetaminophen level were negative. The patient’s LFTs continued to worsen over his hospital course (Image 1). Transfer to a tertiary liver center was not considered due to his tenuous condition, age, and comorbidities. On day five the patient’s AST and ALT started trending down. However, total bilirubin continued to rise, and ALP stayed relatively stable. His respiratory status continued to worsen, and he was eventually transitioned to comfort care. Discussion: In the absence of an established history of liver disease, alcohol abuse, or hepatotoxic drug use, we believe that our patient’s acute liver failure might have been a direct complication of COVID-19 infection. Treatment with 1-2 drugs from the following categories: hepatoprotective, anti-inflammatory, and jaundice-reducing agents including polyene phosphatidyl choline, glycyrrhizic acid, bicyclol, and vitamin E has been proposed to reduce the burden of liver injury. With the increasing number of cases of liver injury with COVID-19, it is pivotal to identify its pathogenesis, acute interventions, and potential long-term complication to treat this life-threatening condition promptly and effectively.Table 1.: demonstrating our patient’s initial labs.Figure 1.: Image 1 demonstrating lab trend of our patient over his hospital stay.

Exploring the efficacy and safety of polyene phosphatidylcholine for treatment of drug-induced liver injury using the Roussel Uclaf causality assessment method: a propensity score matching comparison.

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI).Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores <6 were further evaluated by a panel of hepatologists. The primary outcome was the proportion of patients with ALT normalization at discharge. Propensity score matching was used to identify 183 matched pairs of patients (366 patients in total) from 25,927 patients with DILI.Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups.Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.

A woman with anti-mitochondrial antibody-negative primary biliary cholangitis for a long-term intermittent elevated hepatic enzymes: a case report

: Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver and autoimmune disease. It characterizes the anti-mitochondrial antibody (AMA) positive and detectable in nearly all patients, acting as a major diagnostic and etiological marker. Here, we reported a patient who was diagnosed with PBC while her AMA was negative. It was a rare subtype of PBC with specific characteristics. This patient suffered long-term elevated hepatic enzyme and cirrhosis while without any other hepatic damage symptoms. Strangely, none of the classic serum markers of cirrhotic etiology was positive, including the hepatic virus antigen, AMA, anti-liver/kidney microsome (LKM) antibody, ceruloplasmin. Whereas some systemic immune parameters like erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) appeared unnormal. Moreover, the result of hepatic histology appeared representative PBC. All in all, her test results were unusual and prone to misdiagnosed. After considering all these results carefully and completely. The patient was confirmed diagnosed with AMA negative PBC. With the therapy of ursodeoxycholic acid and polyene phosphatidylcholine, the liver function profile has been increasingly improved. It reminded us in spite that AMA played an important role in PBC diagnose, we should pay attention to the AMA-negative, which usually acts as a puzzle and complicated case prone to misdiagnosis. Besides, we also reviewed the studies till date which containing etiology, characteries and prognosis of AMA-negative PBC, in order to learn more about this novel subtype.

Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4/MyD88/NF-κB pathway.

This study aimed to explore the therapeutic effects and underlying mechanism of berberine (BBR) on the non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD). Rats were randomly divided into the following 4 groups: control (normal diet), model (HFD), polyene phosphatidylcholine HFD+PPC, and BBR (HFD+BBR) group. The NAFLD models were prepared by feeding with HFD for 12 weeks. The liver tissues were observed by oil red O staining. H-E staining was used to detect pathological changes in the liver tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected by an automatic biochemical analyzer. ELISA was performed to observe the inflammatory cytokines (TNF-α, IL-6, and IL-1β) expressions. The levels of TLR4, MyD88, and NF-κB p65 were analyzed using western blot and qRT-PCR, respectively. The nuclear translocation levels of NF-κB in the primary liver cells were measured using flow cytometry. BBR could significantly alleviate the liver tissue steatosis and inflammatory cell infiltration; reduce the NAFLD activity scores and serum levels of ALT, AST, TC, and LDL-C; decrease the levels of TNF-α, IL-6, and IL-1β, and reduce the expression of TLR4, MyD88, and NF-κB in the liver tissues. BBR could also reverse the nuclear translocation of NF-κB in the primary liver cells. BBR alleviated the progress of NAFLD and liver damage, which might contribute to inhibit the nuclear translocation of NF-κB via the TLR4/MyD88/NF-κB pathway.

A real-world data analysis of the use of hepatoprotective drugs in outpatients in six cities of China from 2015 to 2019

Objective To investigate the use of hepatoprotective drugs in China in recent years, and to put forward related suggestions. Methods The outpatient prescription data of hepatoprotective drugs were collected from 85 hospitals in 6 cities of China from 2015 to 2019, and a real-world data analysis was performed to analyze the payment method, issuing department, drug category, and use of hepatoprotective drugs. Results A total of 1 113 575 prescriptions were extracted, involving 38 hepatoprotective drugs such as compound glycyrrhizin, polyene phosphatidylcholine, and bicyclol. Hepatoprotective drugs were mainly in tertiary hospitals, and the highest number of prescriptions containing hepatoprotective drugs were observed in department of infectious diseases, department of gastroenterology, and department of tuberculosis. Anti-inflammatory hepatoprotective drugs accounted for the highest proportion of all prescriptions, mainly compound glycyrrhizin, polyene phosphatidylcholine, and bicyclol. Of all prescriptions, 253 429 (22.76%) had the combination of multiple hepatoprotective drugs, with the highest number of 6 drugs, among which polyene phosphatidylcholine combined with bicyclol accounted for the highest proportion. Conclusion There are large quantities of hepatoprotective drugs used by outpatients in China. At present, the hepatoprotective drugs are clinically applied rationally, but there are still some problems to be solved, such as the combination of drugs.

扶正化瘀片与多烯磷脂酰胆碱治疗非酒精性脂肪肝的疗效比较

扶正化瘀片与多烯磷脂酰胆碱治疗非酒精性脂肪肝的疗效比较

TLR-2-mediated metabolic reprogramming participates in polyene phosphatidylcholine-mediated inhibition of M1 macrophage polarization.

This study aimed to investigate whether the classic hepatoprotective drug polyene phosphatidylcholine (PPC) regulates macrophage polarization and explores the potential role of TLR-2 in this process. In RAW264.7 macrophages and murine bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS), PPC significantly inhibited the production of IL-6, TNF-α, and the mRNA expression of M1-type macrophage markers. Consistently, PPC reduced the mRNA expression of several key enzymes in the pathways of glycolysis and lipid synthesis while increasing the expression of key enzymes associated with lipid oxidation. Moreover, blocking the glycolytic pathway using 2-deoxy-D-glucose (2-DG) significantly enhanced the anti-inflammatory effect of PPC. However, inhibition of lipid oxidation using GW9662 (an inhibitor of PPAR-γ) and GW6471 (an inhibitor of PPAR-α) abolished the anti-inflammatory effect of PPC. Interestingly, TLR-2 expression in macrophages was significantly downregulated after exposure to PPC. Moreover, pre-activation of TLR-2 hampered the anti-inflammatory effect of PPC. In addition, PPC did not inhibit the secretion of IL-6 and TNF-α in TLR-2-/- BMDMs that were activated by LPS. This was consistent with the increased expression of M1 markers and glycolytic and lipid synthesis enzymes but decreased lipid oxidation-related enzymes. These results showed that PPC inhibits the differentiation of M1-type macrophages, which was most likely related to TLR-2-mediated metabolic reprogramming.

Dimethylacetamide-induced toxic hepatitis in spandex workers: clinical presentation and treatment outcomes.

Dimethylacetamide (DMAc) exposure has been associated with toxic hepatitis, and no clinical treatment has been reported. To investigate the clinical manifestations of DMAc-induced symptoms and how to rescue the functional loss due to occupational exposure. Clinical observations of 60 spandex factory workers with the exposure to DMAc from January, 2017-19. Chinese drugs (reduced glutathione, polyene phosphatidylcholine, glycyrrhizin compound, Hugan tablets and ornithine aspartate) were used to evaluate the therapeutic improvements in DMAc-exposed patients. Our data found that 58.3% patients had no distinct clinical symptoms, but 41.7% patients felt fatigue, and 21.7% patients suffered abdominal discomfort and appetite loss, and 8.3% patients had yellow skin and sclera. The ultrasonic and CT imaging revealed that some patients have fatty livers, intrahepatic calcifications, hepatomegaly, gallbladder wall edema and abdominal effusions. Biochemical analysis showed that the alanine aminotransferase (ALT) (P < 0.001), aspartate aminotransferase (AST) (P < 0.001), lactate dehydrogenase (LDH) (P < 0.001) and bilirubin (P < 0.01) statistically decreased after the drug treatment, but alkaline phosphatase (P>0.05) and glutamyl transpeptidase (P>0.05) did not decrease. Twenty-nine out of the thirty-one patients' abnormal blood ammonia recovered. The risk factor of ALT on hospitalization time was significantly related (P < 0.01). The drugs above are sufficient to rescue functional loss in DMAc-induced toxic hepatitis, in part via the regulations of ALT, AST, LDH, bilirubin and ammonia. Workers with the exposure to DMAc should receive specific drugs to maintain the health and prevent functional loss in the long term.

Evaluate the Efficacy and Safety of Polyene Phosphatidylcholine Injection (AYP-101) for the Reduction of Submental Fat

Evaluate the Efficacy and Safety of Polyene Phosphatidylcholine Injection (AYP-101) for the Reduction of Submental Fat

Gut microbiota signatures and lipids metabolism profiles by exposure to polyene phosphatidylcholine.

The aim of the study was to address the causality links and identify specific features of the gut microbiota signatures contributing to host lipids metabolism in the presence or absence of polyene phosphatidylcholine (PPC) administration, and evaluate potential risk of PPC consumption. About 20 C57BL/6J mice were randomly allocated into two groups, normal diet group (CK) and PPC administration group (205.2 mg/kg). Compared with CK group, the contents of unsaturated fatty acids were increased and the saturated fatty acids were decreased in PPC group. The content of free fatty acids (FFA) and lipopolysaccharides (LPS) were significantly decreased (P < 0.05), and expression of carnitine palmitoyltransferase 1A (CPT1A), cluster of differentiation 36 (CD36), liver fatty acid binding protein (L-FABP), fatty acid transport protein 5 (FATP5), and fatty acid synthase (FASN) were significantly decreased in the mRNA and protein levels after treated by PPC (P < 0.05, P < 0.01). Also, we found that acetic acid in feces was significantly increased after consumption of PPC (P < 0.05). After PPC administration the relative abundances of Firmicutes and Clostridia were increased within the phylum level and the class level, respectively. Microbial abundances in genus level were dominated by Lachnospiraceae and Lachnospiraceae_NK4A136_group, whereas the proportion of sequences assigned to Bacteroidetes within the phylum level, class Bacteroidias and Mollicutes, order Anaeroplasmatalesl, genus Bacteroidales_S24-7_group were decreased in metagenomes of treated group with PPC and did not significantly influence on the accumulation of trimethylamine-N-oxide (TMAO). This study revealed that intake of PPC could regulate the gut microbiota signatures and lipids metabolism in mice without TMAO accumulations. © 2019 BioFactors, 45(3):439-449, 2019.

The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data.

To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

Polyene phosphatidylcholine overcomes oxaliplatin resistance in human gastric cancer BGC823 cells

Intrinsic or acquired resistance to oxaliplatin (L-OHP) is a major reason of treatment failure in gastric cancer and limits therapeutic success. Here we generated an oxaliplatin resistant gastric cancer cell line, BGC823/L-OHP, to investigate the effect of a hepatoprotective compound, polyene phosphatidylcholine (PPC), on conquest of oxaliplatin resistance. BGC823/L-OHP cells showed less sensitive to L-OHP directed growth inhibition than the parental BGC823 cells. PPC treatment significantly increased anti-proliferative activity of L-OHP on resistant cells and promoted L-OHP triggered apoptosis, indicating that drug resistance was overcome. Mechanistically, L-OHP incubation stimulated upregulation of an ABC family protein, ABCF2, and the expression was inhibited by PPC. Moreover, expression levels of the stemness factor Nanog and its regulator TLR4 were notably enhanced in BGC823/L-OHP cells and reduced by PPC treatment. To conclude, PPC can overcome oxaliplatin resistance in gastric cancer cells via promoting apoptosis, inhibiting ABCF2, as well via reducing cancer stem cell-like features. The combination therapeutic strategy could serve to increase oxaliplatin effectiveness in the clinic.

Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease

Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus" , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences (P<0.05) except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; P<0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27) µg/L vs. (0.82±0.28) µg/L, P<0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72) µg/L vs. (7.87±3.96)µg/L, P<0.05]. (5) After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant. (6) Compared with before treatment, fecal flora in combined groups was all reduced (P<0.01), but it was comparable before and after treatment in control group. Conclusions: Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

Exenatide improving antioxidant ability of nonalcoholic fatty liver disease of rats

Objective To investigate the exenatide effect on fat-induced nonalcoholic fatty liver disease(NAFLD) of rat. Methods NAFLD models were established after 12 weeks of high fat diet feeding,a total of 120 SD rats were randomly divided into control group(CON group),model group(HFD group),exenatide low,medium,high dose group(ELD group,EMD group,EHD group) and polyene phosphatidylcholine treatment group(PDC group),with 20 rats in each group.After given appropriate treatment,half of the rats were sacrificed after 4 and 8 weeks.HE staining of liver slices,antioxidant factors were performed. Results With the dose of exenatide became larger,and the time got longer,the liver fat and the inflammatory response were significantly reduced and the fat particles were significantly reduced; serum and liver total antioxidant capacity was significantly improved. Conclusion Exenatide improves antioxidant ability of NAFLD of rats. Key words: Non-alcoholic fatty liver disease; Exenatide; Antioxidant ability

The effect and comparison of commonly used liver-protection drugs for irradiated HL-7702 by X

Objective: To investigate the effect of different mechanisms of liver-protection drugs in clinic and compare which one is best for the proliferation of irradiated HL-7702, laying the basis of liver-protection drugs choose in clinic on theory and practice. Methods: Human liver parenchyma cells HL-7702 were given single 6 MV X ray irradiation at a dose of 10Gy, the cells' morphology were detected under an inverted microscope at 24h, 48h and 72h. Then, MTT was used to assess the survival rate of the cells to evaluate the effect of the X ray. The representive medicines which mechanism may relate to RILD were chosen and diluted into various concentrations with culture medium according to clinical and relative reports. Different concentrations of medicines were used to protect the cells damaged by the X ray. Comparing the effect with MTT and measure SOD, MDA for the best one. Further research on its protection of oxidative damage. T-test, F test and non- paramiter test were used for statistical analysis. Results: 2.5 mg/ml and 1 mg/ml of magnesium isoglycyrrhizinate both have an effect on the proliferation of liver cells, especially the concentration of 1 mg/ml. The injection of polyene phosphatidyl choline show trivial effect at the concentrations of 250 μmol/L and reduced glutathione(GSH) did not demonstrate relative functions. Further research on the magnesium isoglycyrrhizinate, found its protection at 48h to oxidative damage (P < 0.05), but the effect is weak at 24h and 48h. Conclusions: In three kinds of representing medicines, magnesium isoglycyrrhizinate has preferable effects on liver parenchyma cells and show a bright future in the treatment of RILD.

Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease.

The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.

The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD.MethodsC57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR.ResultsAt the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered.ConclusionThese findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

Rapid CO breath test screening of drugs for protective effects on ribavirin-induced hemolysis in a rabbit model: a pilot study

Hemolytic anemia is a major side effect of ribavirin antiviral treatment for chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral response and erythropoietin can take several weeks to alleviate anemia. The purpose of the present study was to screen potentially protective drugs against ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO breath test for measuring erythrocyte (RBC) lifespan, the gold standard diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five groups (N = 3/group): one vehicle control group, one ribavirin (only)-treated (RBV) group, and three groups initially treated with ribavirin only, followed by a combination of ribavirin with prednisone (RBV + Pred), polyene phosphatidyl choline (RBV + PPC), or reduced glutathione (RBV + GSH). RBC lifespan was calculated from accumulated CO measured in a closed rebreath apparatus, blood volume measured by the Evan’s blue dye (EBD) dilution test, and hemoglobin concentration data. The RBC lifespan was normal in the vehicle control group (44–60 d), but reduced significantly in all of the ribavirin-treated groups before the addition of screened drugs (17–35 d). RBC lifespan rebounded significantly with the addition of glutathione, but not with the addition of prednisone or polyene phosphatidyl choline. A similar overall drug effect pattern was seen in the hemoglobin concentration and reticulocyte count data. In conclusion, the results of this pilot study indicate that reduced glutathione can attenuate ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our modified rapid CO breath test is feasible and reliable for use in animal studies.