Decrease In Liver Enzymes Research Articles

Hepatoprotective Effect of Cranberry Nutraceutical Extract in Non-alcoholic Fatty Liver Model in Rats: Impact on Insulin Resistance and Nrf-2 Expression.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a pathological accumulation of triglycerides (TGs) in the hepatocyte in the absence of alcohol intake. Untreated NAFLD is expected to progress into liver fibrosis. Cranberry is rich in polyphenols with antioxidant and anti-inflammatory activities.HypothesisThe present study was performed to evaluate our hypothesis of the possible anti-fibrotic effect of cranberry nutraceuticals in a high fat cholesterol diet induced (HFCD)-NAFLD in rats, focusing on improving insulin sensitivity and modulating the expression of nuclear factor erythroid-2-related factor-2 (Nrf2) (a transcription factor responsible for regulating cellular redox balance).MethodMale albino wistar rats (12 weeks) received HFCD and/or cranberry (50 and 100 mg/kg/day, three times/week) orally for 8 consecutive weeks.ResultsIn comparison to the HFCD group, cranberry treated groups (50 and 100 mg/kg) showed marked hepatoprotection, where it significantly decreased liver enzymes (alanine transaminases by 49 and 64% and aspartate transaminases by 45 and 64%; respectively), TGs, and ameliorated the histopathological alterations (such as inflammatory cells infiltration and ballooning degeneration) induced by HFCD. Cranberry also alleviated oxidative stress (malondialdehyde, glutathione, catalase and superoxide dismutase) and inflammation (tumor necrosis factor- alpha, interleukine-6 and nuclear factor kappa-b) and significantly reduced the HOMA-IR and TyG index. On the other hand, cranberry treated groups (50 and 100 mg/kg) showed a marked increase in the expression of adiponectin, by 8 and 13-fold, insulin receptor substrate-2 by 21 and 79%, and Nrf2 by 13 and 61%, respectively. Notably, cranberry significantly reduced the fibrotic markers, TGF–β and α-SMA expression and collagen deposition.ConclusionThe present study showed that cranberry significantly attenuated NAFLD, in a dose dependent manner, which could be partially recognized by its antioxidant, anti-inflammatory activities, and its ability to improve insulin sensitivity. Notably, our study proves for the first time that the anti-fibrotic activity of cranberry is promising.

Liver disease in children and Adolescents with Type1 Diabetes Mellitus

Abstract Glycogenic hepatopathy (GH) is a very rare complication seen mostly in patients with type 1 diabetes mellitus (T1DM) in whom glycemic control has been poor for a long time. We assessed liver diseases in children and adolescents with type 1 diabetes mellitus by detection of elevated liver transaminases and confirmed by fibro scan and ultrasound. One hundred and seven children and adolescents with T1DM were subjected to detailed history, physical examination, laboratory investigation and radiological investigation. Liver transaminases, mean HbA1c and pelviabdominal ultrasound were done for all patients while fibro scan for those with elevated liver enzymes only. Patients with elevated liver enzymes were reassessed after one year. Only nine of our patients have elevated liver enzymes. HbA1c and fibro scan abnormalities (F stage) were significantly higher in patients with elevated liver enzymes. (p < 0.001) After follow up a significant decrease in liver enzymes, fibro scan abnormalities and HbA1c in the group with elevated liver enzymes initially was detected. (p < 0.001) We concluded that liver disease is not a common complication in patients with long standing uncontrolled diabetes which can be reversed after proper control.

Bredemolic Acid Ameliorates Selected Liver Function Biomarkers in a Diet-Induced Prediabetic Rat Model.

Background Prediabetes is an intermediary hyperglycaemic state that precedes type 2 diabetes mellitus (T2DM) in which abnormal metabolism of glucose and lipids occurs in organs such as the liver. Evidence has shown that, about 70% of T2DM patients develop hepatic dysfunction which is found to begin during the prediabetic stage. Bredemolic acid, a pentacyclic triterpene, has been found to improve insulin sensitivity in diet-induced prediabetic rats. The effects of this compound on liver function, however, are unknown. This study was therefore designed to investigate the effects of BA on liver function in high fat-high carbohydrate (HFHC) diet-induced prediabetic rats. Methods Thirty-six (36) male rats that weigh 150 g–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (Results The induction of prediabetes resulted in increased release of liver enzymes (AST and ALT), increased liver glycogen and triglyceride, lipid peroxidation, and decreased sterol regulatory element-binding protein (SREBP1c) and antioxidant enzymes. However, the administration of BA decreased liver enzyme concentrations, decreased hepatic oxidative stress, and improved antioxidant enzymes such as SOD and GPx. Conclusion BA administration improved liver function in diet-induced prediabetic rats in the presence or absence of dietary intervention.

RecombinantLactococcus lactisExpressing Ling Zhi 8 Protein Ameliorates Nonalcoholic Fatty Liver and Early Atherogenesis in Cholesterol-Fed Rabbits

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, including dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome, all of which lead to lipid deposition in the liver causing inflammation and fibrosis. Several clinical trials have shown that certain Chinese herbal medicines with anti-inflammatory effects can be used as adjuvant therapy to prevent the development of cardiovascular events and liver disease. Ling Zhi 8 (LZ8) is an immunomodulatory protein isolated from a medicinal mushroom and has been well documented to possess a broad range of pharmacological properties. This study aimed to evaluate the protective effects of recombinant Lactococcus lactis expressing LZ8 protein on NAFLD and atherogenesis in a cholesterol-fed rabbit model. Twelve rabbits were divided into three groups and fed with syrup only, L. lactis vehicle, or recombinant L. lactis-LZ8 once a day on weekdays for five weeks, respectively. The gene expression of IL-1β in the aorta was significantly suppressed after oral administration of L. lactis-LZ8. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the subendothelial space. LZ8 also inhibited the expression of IL-1β in the liver, decreased fat droplet deposits and infiltration of inflammatory cells, and improved liver function by decreasing liver enzymes in an animal model. Our results suggest that the Lactococcus-expressing LZ8 appears to be a promising medicine for improving both NAFLD and early atherogenesis owing to its anti-inflammatory effect. Furthermore, it is available as a low-cost food-grade product.

Salvia hispanica (Chia) seeds afford hepatoprotection against Isoniazid and Rifampicin induced toxicity in a murine model

Salvia hispanica L. (chia) seeds are a rich source of omega-3 fatty acid and polyphenolic compounds with documented antioxidant property protecting against oxidative stress, which is implicated in the pathophysiology of drug-induced hepatotoxicity. Hence, the present study evaluates the effects of Salvia hispanica seeds in an animal model of antitubercular drug induced hepatic damage. Adult wistar rats were divided into six groups; normal control, hepatotoxic control, test groups treated orally with ground Salvia hispanica seeds at doses 250,500 and 1000mg/day respectively, standard control receiving silymarin at a dose of 50mg/kg orally. Hepatotoxicity was induced by administering isoniazid with rifampicin at a dose of 100mg/kg each intraperitoneal. After administration of drugs for a period of 21 days, the blood samples were evaluated for estimation of liver enzymes (AST, ALT, and ALP), total protein, albumin and total bilirubin and the liver was dissected and sent for histopathological evaluation. The hepatotoxic group showed a significant increase in liver enzymes and total bilirubin compared to normal control. There was a significant decrease in liver enzymes and total bilirubin in the drug treated and silymarin treated groups when compared to the control. However, there was no significant difference in protein and albumin between groups. Histopathological evaluation of the liver further confirmed the hepatoprotective potential of the seeds of Salvia hispanica. Salvia hispanica seeds protect against drug induced liver injury in a murine model and the underlying mechanism can be accorded to its antioxidant activity.

Investigating the impact of silymarin on liver oxidative injury.

Introduction:Various drugs affect liver problems caused by general hypoxia, including silymarin. Due to the fungal killer toxins, nowadays, silymarin (milk thistle) is used as an effective drug in the prevention and treatment of liver diseases and liver toxicity. In addition, silymarin protects the liver cells from solvents and chemical substances. The aim of this paper is to investigate the impact of silymarin on liver problems induced by general hypoxia.Material and Methods:This study was a double-blinded clinical trial on patients with hypoxia who referred to the hospital emergency department. Patients were randomly divided into case and control groups. The case group was treated with silymarin at a dose of 280 mg with orally gavage technique and the control group was treated with a placebo every 8 h for 3 days. To investigate the leukocytosis, liver enzymes levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), prothrombin time (PT), partial thromboplastin (PTT), international normalized ratio (INR), and white blood cell (WBC) were measured before and after the intervention. SPSS 21 software was used to analyze the data.Results:In the silymarin group, liver enzymes were lower than the placebo group on the third day after treatment (P < 0.05). There was no significant difference between the two groups in terms of coagulation factors and WBC count on the third day after treatment (P > 050). On the third day after treatment, the amount of GGT was lower in the silymarin group (P < 0.05).Conclusion:Silymarin decreased liver enzymes (ALT, AST, and CPK) and the level of GGT. Therefore, it is recommended to be used in patients with hypoxic liver injury.

The possible protective role of omega 3 on liver of L thyroxine treated male albino rats. Histological and immunhistochemical study

Background: Hyperthyroidism is a condition associated with oxidative damage of liver. Omega-3 fatty acids are effective in various medical conditions due to antioxidant, anti-inflammatory, anti-apoptotic and anti-fibrotic activities.Aim of the work: Here we evaluate the potential effects of omega-3 fatty acids on experimentally induced hyperthyroidism. Materials and methods: Thirty adult male rats were divided equally into 3 groups; Control group (G1) received saline. Hyperthyroid (GII) received L-thyroxine group 0.1μg/g/day intraperitoneal for 6 weeks. L-thyroxine+Omega-3 group (GIII) received L-thyoxine as previous group then 12% of eicosapentaenoic acid (EPA), and 18% of docosahexaenoic acid (DHA) for 4 weeks (from 3rd to 6th weeks). Blood samples were taken for detection of liver enzymes, serum T3 and TSH. Liver samples were taken for light and electron microscopic examination. Immunohistochemical staining of CD68, Caspase 3 and proliferating cell nuclear antigen (PCNA) were done.Results: L-thyroxine over dose decreased TSH, increased serum T3 and liver enzymes (ALT &AST). Also, it induced patches of cytoplasmic vacuolation, dense nuclei, vascular congestion and significant increase of collagen fibers. Electron microscopic changes revealed rarified cytoplasm and mitochondria with destructed cristae in most hepatocytes, . Significant increase of caspase3 and CD68 immunoexpression and significant decrease of (PCNA) immunoexpression were noticed. Concomitant treatment with omega 3 showed decreased liver enzymes and T3. Improvement of most morphological alterations in the hepatocytes was observed. Significant decrease of collagen fibers, caspase 3 and CD68 immunoexpression was observed and significant increase of PCNA immunoexpression.Conclusion: Combined treatment with omega 3 ameliorated most of L. thyroxine induced liver changes and serological parameters.

Chrysin Effect in Prevention of Acetaminophen-Induced Hepatotoxicity in Rat.

Acetaminophen is a commonly used analgesic drug that induces hepatotoxicity at high doses and produces the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) through oxidase isoenzyme system. The antioxidant and anti-inflammatory activity of flavonoid chrysin has been reported in different studies. The present study was conducted to investigate the protective effect of chrysin on acute acetaminophen-induced hepatotoxicity. The cytotoxicity of chrysin on fibroblast cells was evaluated using MTT assay, and then, 54 rats were divided into nine groups of six, and acetaminophen (1500 mg/kg) was administered in all groups except for the control group, second and the seventh groups (40 mg/kg), and all groups were treated with chrysin for 14 days. Liver enzymes, inflammatory factors TNF-α and IL-2, and total antioxidant activity were measured in serum while liver tissue was histopathologically examined. Based on the MTT assay results, 31.25, 62.5, 125, 250, and 500 μg/mL chrysin had no adverse effects on healthy fibroblast cells (P < 0.05). Chrysin decreased the level of liver enzymes (ALT, AST, and ALP), which were previously increased after the use of acetaminophen (p < 0.05). The hepatoprotective effect and total antioxidant capacity increased in a dose-dependent manner and the effect of the highest concentration of chrysin was equal to the effect of silymarin (P < 0.05). TNF-α in groups 4 to 6 decreased in a dose-dependent manner (P = 0.04), and chrysin did not show any significant reducing effect on IL-2 compared to silymarin. Chrysin prevents the necrosis and injury of acute acetaminophen-induced hepatotoxicity by decreasing liver enzymes and TNF-α and increasing total antioxidant capacity and protecting the liver tissue.

Silver nanoparticles as a therapeutic agent in experimental cyclosporiasis

Cyclosporiasis is an emerging worldwide infection caused by an obligate intracellular protozoan parasite, Cyclospora cayetanensis. In immunocompetent patients, it is mainly manifested by self-limited diarrhea, which is persistent and may be fatal in immunocompromised patients. The standard treatment for cyclosporiasis is a combination of two antibiotics, trimethoprim and sulfamethoxazole. Gastrointestinal, haematologic and renal side effects were reported with this combination. Moreover, sulfa allergy, foetal anomalies and recurrence were recorded with no alternative drug treatment option. In this study, silver nanoparticles were chemically synthesized to be evaluated for the first time for their anti-cyclospora effects in both immunocompetent and immunosuppressed experimental mice in comparison to the standard treatment. The effect of silver nanoparticles was assessed through studying stool oocyst load, oocyst viability, ultrastructural changes in oocysts, and estimation of serum gamma interferon. Toxic effect of the therapeutic agents was evaluated by measuring liver enzymes, urea and creatinine in mouse sera. Results showed that silver nanoparticles had promising anti-cyclospora potentials. The animals that received these nanoparticles showed a statistically significant decrease in the oocyst burden and number of viable oocysts in stool and a statistically significant increase in serum gamma interferon in comparison to the corresponding group receiving the standard treatment and to the infected non-treated control group. Scanning electron microscopic examination revealed mutilated oocysts with irregularities, poring and perforations. Biochemical results showed no evidence of toxicity of silver nanoparticles, as the sera of the mice showed a statistically non-significant decrease in liver enzymes in immunocompetent subgroups, and a statistically significant decrease in immunosuppressed subgroups. Furthermore, a statistically non-significant decrease in urea and creatinine was recorded in all subgroups. Thus, silver nanoparticles proved their effectiveness against Cyclospora infection, and this will draw the attention to its use as an alternative to the standard therapy.

P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits

Abstract Background Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities. Methods and findings In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes. Figure 1 Conclusions Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect. Acknowledgement/Funding TCVGH-1067317C, TCVGH-1063108C

Toxicity and tissue distribution of methylsulfonylmethane following oral gavage in broilers

An experiment was conducted to investigate the toxicity and tissue distribution of methylsulfonylmethane (MSM) following oral gavage in broilers. A total of four hundred and thirty-two 15-day-old Ross 308 male broilers were allotted to 6 treatments with 6 replicates of 12 birds per replicate and administered a single oral dose of MSM at 0, 50, 100, 300, 1,000, or 2,000mg/kg BW (Study 1). Another one hundred and sixty-eight 3-day-old chicks were allotted to either control or test group (Study 2) and administered a daily oral gavage of either 0 or 1, 500mg/kg BW of MSM for 21 D consecutively. Blood and tissue samples were collected over a 48h (Study 1) or 21 D (Study 2) period and analyzed for MSM concentrations. Toxicity was assessed through changes in hematology and clinical blood chemistry. In Study 1, plasma MSM concentrations were below 167μg/mL at all time-points in birds receiving up to 300mg/kg BW, and were significantly higher (P < 0.05) in birds receiving 1,000 or 2,000mg/kg BW. Similarly, only the highest 2 MSM dosages elicited increased lymphocyte and decreased heterophil counts at 8h (P < 0.003) and decreased hematocrit at 48h (P = 0.015). Growth performance variables were unaffected by MSM in Study 2, and plasma and tissue MSM concentrations were highest on study day 21, with MSM-dosed birds always exhibiting higher (P < 0.03) concentrations compared with the control. Birds in Study 2 that were dosed with MSM had decreased liver enzyme concentrations at day 7 and 21 and decreased glucose and phosphorus at day 7. Importantly, MSM was detected in plasma and all tissues of control groups, confirming that MSM is synthesized de novo in chickens. In conclusion, oral MSM at either acute (single dose at 1,000 to 2,000mg/kg BW) or sub-chronic (1,500mg/kg BW daily for 21 D) concentrations did not cause any adverse effects on growth or clinical outcomes and appeared to be absorbed and distributed throughout the body.

Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/ Reperfusion Injury during Liver Transplantation.

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

Vitamin C &lt;i&gt;in-vivo&lt;/i&gt; Effect on Liver Enzymes and Some Endogenous Antioxidants in Paracetamol-Induced Model of Liver Toxicity on Wistar Rats

This study aimed at assessing the in-vivo effect of Vitamin C on liver enzymes and some endogenous antioxidants in paracetamol-induced model of liver toxicity on Wistar rats. The rats were grouped into four groups of five animals each; groups 1 and 2 were control (positive and negative), while group 3 and 4 received vitamin C 500 mg/kg and silymarin 100 mg/kg respectively. Dosing was oral and daily for 6 days according to their body weights. All the animals except the positive control group (Group 1) were administered paracetamol 3 g/kg on the 7th day, and then observed for 24 hours before sample collection for biochemical indices and liver histological studies. Paracetamol caused a significant (p&lt;0.05) increase in liver enzymes, significant (p&lt;0.05) decrease in antioxidant enzymes, and necrosis in liver tissues when compared to the control. Administration of 500 mg/kg Vitamin C prior to induction of liver damage by PCM resulted in significant (p&lt;0.05) decreased liver enzyme and well as an increase in the antioxidant enzymes. Pre-treatment of the animals with vitamin C showed a reversal of the toxic effect of paracetamol on the rats.Keywords: Vitamin C, liver enzymes, paracetamol, toxicity.

Relation between microRNA‐21, transforming growth factor β and response to treatment among chronic hepatitis C patients

Persistence of hepatitis C virus(HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments. The current study aimed to investigate the relation between miRNA-21 expression profiles, transforming growth factor β (TGF-β) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients. This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real-time polymerase chain reaction and TGF-β1 serum levels were measured by using enzyme-linked immunosorbent assay. There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA-21 (P = .001*) and serum levels of TGF-β1 ( P = .337) among HCV patients after receiving treatment. Nearly all responders to direct antiviral drugs showed increased levels of both miRNA-21 and TGF-β1. This may indicate an interplay between TGF-β1 and miRNA-21 during remission or progression of viral infection. Thus miRNA-21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.

132-OR: Effects of Dapagliflozin, an SGLT2 Inhibitor, on Hepatic Steatosis and Fibrosis Evaluated by Transient Elastography in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Objective: To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Research Design and Methods: In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin (5 mg/day) group (n=33) or to the control group (n=24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed by using a transient elastography (FibroScan) to measure the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Results: At baseline, LSM was positively correlated with several markers and scoring systems for liver fibrosis in a total of 57 patients with T2D and NAFLD. In week 24, CAP showed a significant decrease from 314±61 to 290±73 dB/m (P=0.0424) in the dapagliflozin group, while there was no significant change in the control group. In addition, LSM tended to decrease from 9.49±6.05 kPa to 8.01±5.78 kPa in the dapagliflozin group. In 14 patients from this group with LS values ≥8.0 kPa, indicating significant liver fibrosis, LSM decreased significantly from 14.7±5.7 to 11.0±7.3 kPa (P=0.0158). Furthermore, serum alanine aminotransferase and γ-glutamyltranspeptidase levels decreased in the dapagliflozin group, but not in the control group, and visceral fat mass was significantly reduced in the dapagliflozin group. Conclusions: Based on these findings, the SGLT2 inhibitor dapagliflozin improves liver steatosis in parallel with a decrease of liver enzymes in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis in only patients with significant liver fibrosis. (UMIN000022155) Disclosure Y. Aso: Research Support; Self; Ono Pharmaceutical Co., Ltd. T. Jojima: None. T. Iijima: None. I. Usui: None.

COMPARATIVE EVALUATION OF IN VITRO ANTIOXIDANT AND IN VIVO HEPATOPROTECTIVE ACTIVITIES OF ETHANOLIC LEAF AND ROOT EXTRACTS OF CLEOME GYNANDRA

In vitro antioxidant and in vivo hepatoprotective activities of Cleome gynandra ethanolic leaf and root extracts were assessed. In vitro antioxidant activity was carried by DPPH, Nitric oxide, hydroxyl radical and phosphomolybdenum assays. Hepatoprotective activity was evaluated by Carbon tetrachloride (CCl4) induced hepatotoxicity in albino rats.The animals were divided into seven groups (Four test groups - Ethanolic Leaf and Root Extracts of Cleome gynandra of 100 mg/kg and 200 mg/kg, standard silymarin (100 mg/kg), toxic control-carbon tetrachloride and vehicle). On the eight day, the blood was collected and parameters like serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP) and Total bilirubin (TB) were estimated. Significant antioxidant status with good IC50 values similar to standard ascorbic acid was obtained. A significant decrease in liver enzymes was observed in test groups comparable to silymarin. From the results obtained, ethanolic leaf extract has contributed better hepatoprotection compared with root extract in experimental rats.

Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients.

Hepatitis E virus (HEV) genotype 3 infection frequently progresses to chronic disease with persisting HEV viremia in immunocompromised patients. Here, we evaluated the prevalence of HEV infection in renal allograft recipients and investigated the efficacy and tolerability of ribavirin monotherapy. A total of 947 recipients on average 8.7years post transplant were screened for anti-HEV IgG, IgM and HEV-RNA. Sixteen HEV-viremic renal allograft recipients were treated with ribavirin for 12weeks. HEV-RNA concentration, laboratory and clinical parameters were assessed at baseline, during therapy and 12weeks after treatment cessation. HEV-genotyping was performed in all HEV-viremic patients. Past HEV infection was detected serologically in 18% of the renal allograft recipients. Ongoing HEV replication was found in 16 recipients (all genotype 3). Unanimously, distinct HEV sequences were revealed in all HEV-viremic patients. At the start of ribavirin treatment, median HEV-RNA viral load was 4.3×106 (8000-5.0×106 )IU/mL. Ninety-four percentage of HEV-infected allograft recipients showed a sustained virological response 12weeks after treatment cessation. Ribavirin treatment was associated with rapid decrease in liver enzymes and rare occurrence of anemia. Prevalence of active HEV infection is important in renal transplant patients without signs of nosocomial infection. Ribavirin treatment was safe and effective.

Good Response of Lupus Hepatitis to Mycophenolate Mofetil and Belimumab as of Lupus Exanthema to Rituximab: A Case Report

A 66-year-old male patient had been primarily treated for cutaneous lupus erythematosus 15 years ago. He received local corticosteroids and following systemic immunosuppressants: methylprednisolone (MP), chloroquine (removed due to retinal haemorrhage), cyclosporine A and azathioprine (both removed due to non-response). Due to polyarthralgia methotrexate as well as golimumab were started. Despite good response, both drugs had to be stopped due to development of hepatitis confirmed by liver biopsy (virus serological tests were negative). Early after onset of a combination treatment with 1 g mycophenolate mofetil (MMF) per day orally and 10 mg/kg belimumab intravenously at weeks 0, 2, 4, followed by every 4 weeks, a marked decrease in liver enzymes could be detected. Due to insufficient response of lupus exanthema, hydroxychloroquine (HCQ) was added. After 9 months of belimumab administration, the biologic therapy was switched to rituximab (1000 mg intravenously at weeks 0 and 2) in order to achieve a better control of cutaneous manifestation. Surprisingly, after the very first infusion a rapid and marked improvement of lupus exanthema was noticed. Such an improvement had not been experienced since 2003. We could confirm an excellent response of systemic lupus erythematosus (SLE)-associated hepatitis as well as arthralgias to MMF and belimumab. Additionally, there was an excellent and prompt response of SLE-associated skin lesions to rituximab and MMF, despite the fact, that these drugs are still not approved for treatment of SLE. Verbal informed consent was obtained from the patient for the presentation of his disease course and images.

Hepatic and renal toxicity and associated factors among HIV-infected children on antiretroviral therapy: a prospective cohort study.

The aim of the study was to investigate the prevalence of renal function and liver enzyme abnormalities among HIV-infected children, changes in prevalence with time on combination antiretroviral therapy (cART), and the factors associated with these abnormalities. A prospective cohort study was conducted among HIV-infected children < 18 years old (n = 705) who were on first-line cART. Liver enzymes, renal function, haematology, immunology and virological response were assessed at enrolment and followed bi-annually for 18 months. Liver fibrosis and cirrhosis were assessed using noninvasive markers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis score (FIB-4). The median age was 12 [interquartile range (IQR) 8-14] years; 53.3% of patients were male. At enrolment, the median cART duration was 3.3 (IQR 1.1-6.1) years; 177 (25.1%) and 83 (11.8%) patients had elevated AST and alanine aminotransferase (ALT), respectively. A tenth of the children had an APRI score > 0.5, suggesting liver fibrosis. Being on a zidovudine (ZDV)- or nevirapine (NVP)-based regimen and having a viral load > 1000 HIV-1 RNA copies/mL were significantly associated with elevated ALT. Twenty-four (3.4%) and 84 (12.1%) patients had elevated creatinine and blood urea nitrogen (BUN), respectively. As cART duration increased by 6 months, median BUN increased by 1.6 [95% confidence interval (CI) 0.4-2.7] mg/dL (P = 0.01); the glomerular filtration rate (GFR) decreased by 35.6 (95% CI 17.7-53.4) mL/min/1.73 m2 (P < 0.0001); and AST and ALT decreased by 1.4 (95% CI 0.4-2.5) IU/L (P = 0.01) and 1.4 (95% CI 0.2-2.6) IU/L (P = 0.01), respectively. A high prevalence of liver enzyme and renal function abnormalities was observed at enrolment. Decreasing liver enzyme levels during follow-up are possibly reassuring, while the progressive reduction in GFR and the increase in BUN are worrisome and require further study.

Biochemical Activity and Hypoglycemic Effects of Rumex obtusifolius L. Seeds Used in Armenian Traditional Medicine.

Diabetes mellitus (DM) is a serious chronic metabolic disorder. Various diseases are being treated with medicinal plants and that is because of the less side effects of the current therapy. The diversity of plants in Armenia is due to the singularity of natural environment. However, biochemical activity of these plants has not been studied well. Thus, the goal was to investigate biochemical activity and antihyperglycemic properties of Rumex obtusifolius L. in rabbits with hyperglycemia. The high content of total phenolic compounds, flavonoids, and tannins has been determined in this plant extract. Oral administration of ethanol extract showed significant effect on hyperglycemia, reducing fasting glucose levels (57.3%, p<0.05), improving glucose tolerance, and increasing liver glycogen content (1.5-fold, p<0.01) compared to the hyperglycemic control group. Furthermore, ethanol extract of R. obtusifolius reduced total cholesterol, low-density lipoprotein cholesterol levels, and vice versa increased high-density lipoprotein cholesterol levels and also decreased liver enzymes levels (alanine aminotransferase and aspartate aminotransferase) compared with untreated group. These findings suggest that R. obtusifolius may have beneficial effects and should be supplement, as herbal remedy in the treatment of DM.