Whether cellular apoptosis is a primary mechanism promoting steatohepatitis or is a secondary phenomenon resulting from tissue inflammation is under investigation, but the evidence that PGC-1β seems to avoid cell death in steatotic

liver suggests an important role of this coactivator in cellular survival during the development of NASH, thus avoiding the causal relationship between apoptosis and fibrosis that could lead to the progression of steatohepatitis to more severe liver diseases, such as cirrhosis and hepatocarcinoma. Taken together, our findings suggest PGC-1β coactivator as a potential player in the hepatocyte protection against steatohepatitis. Indeed, the ability of PGC-1β mice to induce mitochondrial β-oxidation and promote find more TG clearance in the blood, together with the ability to conserve the Z-VAD-FMK clinical trial expression of metabolic pathways whose transcription is greatly compromised during steatohepatitis, might be the main

mechanisms by which PGC-1β overexpression protects liver from steatohepatitis. In support of the theory that PGC-1β is able to protect from steatohepatitis acting on lipid accumulation through mitochondrial functions and TG clearance, its constitutive activation in mice fed an HFD diet protected also against steatosis. In contrast with previous studies that reported that the PGC-1β dependent up-regulation of mitochondrial proteins is not sufficient to prevent lipid overload in animals fed with HFD,20 in our models hepatic triglyceride and cholesterol levels are greatly reduced, leading to an improvement of steatotic phenotype. These discrepancies could be due to the different models used for this study, since our mice with constitutive overexpression of PGC-1β were challenged with a chronic high-fat feeding. 上海皓元 Nevertheless, it could be interesting to better investigate the differences between acute and chronic overexpression of this coactivator with short- and long-term steatogenic diets. In conclusion, this work bolsters the concept that a combined action

of PGC-1β on lipid synthesis and secretion, as well as on mitochondrial β-oxidation and oxidative phosphorylation, could ameliorate liver disease in steatosis and steatohepatitis progression. We thank S.A. Kliewer, J.M. Taylor, and A. Vidal-Puig for their tools and support. Additional Supporting Information may be found in the online version of this article. “
“See article in J. Gastroenterol. Hepatol. 2012; 27: 888–892. Helicobacter pylori (HP) infection affects 70–90% of the population in developing countries and 25–50% in developed countries.1 HP causes chronic gastritis and development of various gastric and extra-gastric diseases, such as peptic ulcer, stomach cancer, MALToma and adult idiopathic thrombocytopenic purpura.2,3 Eradication of HP has been shown to be effective for preventing and treating such diseases. Therefore, world-wide eradication of HP has long been a desired objective.

The same HCV RNA selleck compound assay was used for Studies P05216, C216, and 108, so we are not aware of an obvious, biologically plausible explanation for a higher

rate of transient detectable/BLOQ HCV RNA levels during follow-up among SVR subjects in Study 108. However, both P05216 and C216 used the same contract laboratory for HCV RNA analyses, whereas a different contract laboratory was used for Study 108. Differences in assay performance related to the specific laboratory performing the analyses could be a possible explanation of different reporting frequencies of low level, detectable HCV RNA. As shown in Table 2, among subjects who achieved SVR (based on

at any point during follow-up, and less than 1% of all follow-up results from SVR-achieving subjects were reported as detectable. All of these detectable HCV RNA measures were either below or near the assay LLOQ. In contrast to the Vendor A results reported for C216 and P05216, for Study 108, Vendor B reported a 9% frequency (>15- and 45-fold higher than P05216 and C216, respectively) of detectable follow-up FK506 mouse HCV RNA among SVR-achieving subjects, representing 24% of all SVR subjects (Table 2). As in C216 and P05216, all of these detectable HCV RNA measures were either below or near the assay LLOQ. Reanalyses conducted by Vendor A for a subset of Study 108 samples from follow-up and various on-treatment timepoints yielded a reduced frequency of detectable/BLOQ HCV RNA results. The extent of this reduced frequency of detectable/BLOQ results varied by timepoint. For samples reported as detectable/BLOQ by Vendor B, 40% and 70% of those from week 4 and week 12 on-treatment timepoints, respectively, and 92% for follow-up timepoints, were reported by Vendor A as undetectable. Taken together, the higher

frequency of follow-up detectable/BLOQ results from SVR subjects 上海皓元 reported by Vendor B for Study 108 correlated with the higher frequency of detectable/BLOQ results reported during treatment, and was associated with less difference in SVR rates based on detectable/BLOQ versus undetectable HCV RNA during treatment. Our analyses of boceprevir and telaprevir clinical trials indicate that undetectable and detectable/BLOQ HCV RNA levels during treatment are qualitatively different, and this difference is clinically relevant. An on-treatment HCV RNA level that is detectable/BLOQ is, on average, indicative of a reduced virologic response compared with an HCV RNA level that is undetectable at the same timepoint.

Till final follow-up, BBS resolution without stenting was achieved in 4 patients. Intraductal RFA appears to be safe and effective for the management of BBS, however, randomized studies with longer follow-up are warranted. Key Word(s): 1. ERCP; 2. biliary

stricture; Presenting Author: NING CHEN Additional Authors: LIMING ZHANG, YULAN LIU Corresponding Author: YULAN LIU Affiliations: Peking University People’s Hospital Objective: Multiple primary malignant neoplasm had been reported occasionally, but cases which diagnosed at the early stage of the simultaneous carcinomas and been treated successfully by mini-traumatic therapies are rare. Here we report Sirolimus research buy such a case. Methods: A 64-year old male presented with recurrent epigastric discomfort for 6 months.

He had no past history of any other chronic diseases. Gastroscopy showed a 4 * 2 cm lesion with coarse plica mucosa at the antrum. Narrow Band Imaging (NBI), magnifying endoscopy and endoscopic ultrasonography indicated the lesion to be a early carcinoma, localized to mucosa. Histology of biopsies showed severe dysplasia and intramucosal carcinoma. Endoscopic submucosal dissection (ESD) was planned to perform and the patient was hospitalized. When undergoing routine examination, chest see more X ray found a possible malignant mass in the left upper lung and abdominal CT scan suspected carcinoma in gall bladder. Initially, mass in the lung had been suspected to be metastasis from stomach and if that was the case, ESD is contraindicated and surgery plus chemotherapy should be considered. But after careful discussion with thoracic surgeon and radiologist, mass in the lung was considered to be a primary neoplasm and should 上海皓元医药股份有限公司 be treated after ESD by thoracoscope, since thoracoscope may damage pulmonary function and delay the ESD. The mass in gall bladder was thought to be a individual neoplasm and laparoscopic cholecystectomy was recommended. Results: ESD was then

performed in the first step, followed by laparoscopic cholecystectomy, when histology showed Xanthogranulomatous Cholecystitis. 1 month later, biopsy during thoracoscope confirmed adenocarcinoma in the lung by frozen section and left upper lobe was resected. Conclusion: The patient had been followed up for 1 year and been well. Key Word(s): 1. gastric carcinoma; 2. ESD; Presenting Author: ZHI QUN LI Additional Authors: ENQIANG LINGHU, JIANGYUN MENG, HONGBIN WANG, XIANGDONG WANG Corresponding Author: ENQIANG LINGHU Affiliations: Department of Gastroenterology and Hepatology, the Chinese PLA General Hospital; Department of Gastroenterology and Hepatology, the PLA General Hospital Objective: Validate and improve the accuracy, feasibility of endoscope measurement ruler to measure the diameter of esophageal and gastric varices.

Till final follow-up, BBS resolution without stenting was achieved in 4 patients. Intraductal RFA appears to be safe and effective for the management of BBS, however, randomized studies with longer follow-up are warranted. Key Word(s): 1. ERCP; 2. biliary

stricture; Presenting Author: NING CHEN Additional Authors: LIMING ZHANG, YULAN LIU Corresponding Author: YULAN LIU Affiliations: Peking University People’s Hospital Objective: Multiple primary malignant neoplasm had been reported occasionally, but cases which diagnosed at the early stage of the simultaneous carcinomas and been treated successfully by mini-traumatic therapies are rare. Here we report Alvelestat molecular weight such a case. Methods: A 64-year old male presented with recurrent epigastric discomfort for 6 months.

He had no past history of any other chronic diseases. Gastroscopy showed a 4 * 2 cm lesion with coarse plica mucosa at the antrum. Narrow Band Imaging (NBI), magnifying endoscopy and endoscopic ultrasonography indicated the lesion to be a early carcinoma, localized to mucosa. Histology of biopsies showed severe dysplasia and intramucosal carcinoma. Endoscopic submucosal dissection (ESD) was planned to perform and the patient was hospitalized. When undergoing routine examination, chest NVP-AUY922 nmr X ray found a possible malignant mass in the left upper lung and abdominal CT scan suspected carcinoma in gall bladder. Initially, mass in the lung had been suspected to be metastasis from stomach and if that was the case, ESD is contraindicated and surgery plus chemotherapy should be considered. But after careful discussion with thoracic surgeon and radiologist, mass in the lung was considered to be a primary neoplasm and should 上海皓元医药股份有限公司 be treated after ESD by thoracoscope, since thoracoscope may damage pulmonary function and delay the ESD. The mass in gall bladder was thought to be a individual neoplasm and laparoscopic cholecystectomy was recommended. Results: ESD was then

performed in the first step, followed by laparoscopic cholecystectomy, when histology showed Xanthogranulomatous Cholecystitis. 1 month later, biopsy during thoracoscope confirmed adenocarcinoma in the lung by frozen section and left upper lobe was resected. Conclusion: The patient had been followed up for 1 year and been well. Key Word(s): 1. gastric carcinoma; 2. ESD; Presenting Author: ZHI QUN LI Additional Authors: ENQIANG LINGHU, JIANGYUN MENG, HONGBIN WANG, XIANGDONG WANG Corresponding Author: ENQIANG LINGHU Affiliations: Department of Gastroenterology and Hepatology, the Chinese PLA General Hospital; Department of Gastroenterology and Hepatology, the PLA General Hospital Objective: Validate and improve the accuracy, feasibility of endoscope measurement ruler to measure the diameter of esophageal and gastric varices.

The median age was 63.5 years

(IQR: 7.2). The cohort was predominantly male (84%) and black (55%). The median time elapsed since KT was 4.1 years (IQR: 3.5), the median GFR was 51 ml/min (IQR: 19.0), and the median HCV VL was 1.4 million IU/ml (IQR: 3.5). The most frequent genotypes were 1a (45%) and 1b (30%). Fifteen (35%) patients had previously failed HCV Tx prior to KT. Forty-two (63%) patients had a liver biopsy prior to KT, revealing advanced fibrosis (F3-F4) in 7 (17%). Four (6%) patients developed cirrhosis (1 with advanced fibrosis pre-KT, 2 without advanced fibrosis pre-KT and 1 without any biopsy) after KT. Less than half of the Tx eligible cohort had regular F/U with a GI or hepatologist. In univariate analysis, prior LT (OR 2.08, p=0.005), diagnosis of cirrhosis (OR 2.17, p=0.036) and prior HCV Tx (OR 1.71, p=0.05) were associated with regular liver F/U. Conclusion: A strategy to identify KT recipients selleck chemicals with chronic HCV for IFN-free therapies demonstrated that over half were eligible for Tx. However, only half of the patients had regular F/U with a GI/hepatologist. this website These results suggest a need for pro-active identification and assessment of HCV infected patients in this newly eligible population by transplant centers. Disclosures: Joseph A. Odin – Advisory Committees or Review Panels: Bristol

Meyers Squibb, AbbVie Douglas Dieterich – Advisory Committees or Review Panels: merck, Idenix, Jans-sen ; Consulting: Gilead, BMS Thomas D. Schiano – Advisory Committees or Review Panels: vertex, salix, merck, gilead, pfizer; Grant/Research Support: massbiologics, itherx The following people have nothing to disclose: Genevieve Huard, Anna Patel, Brian Kim, Badr Aljarallah, Ponni Perumalswami, Sara Geatrakas, Jawad Ahmad, Vinay Nair, Gene Y. Im BACKGROUND: People who inject drugs (PWID) have historically been perceived to have “difficult to treat” disease, with physicians citing concerns 上海皓元医药股份有限公司 regarding compliance, assumed high re-infection rates and perceived inferior treatment

outcomes. METHODS: A retrospective analysis of outcomes to anti-HCV therapy (pegylated interferon and ribavirin) in PWID was undertaken at our institution from 2002 – 2012, and compared to non-PWID patients receiving identical therapy. Analysis of SVR, discontinuation rates, and re-infection rates were recorded. Of 1,071 patients included in the study, the PWID subgroup comprised 724 patients who had a remote or recent history of injecting drug use with 347 patients in the non-PWID subgroup having other defined risk factors for HCV. Baseline characteristics of each group are outlined in table 1. RESULTS: SVR rate in the PWID cohort was 64.2% compared to 62.2% in the non-PWID group, and no statistically significant difference in SVR was observed across genotypes (Table 1). Furthermore, there was no difference in the number of patients failing to complete treatment (8.3% in the PWID group vs 7.2% in the non-PWID group).

A possible explanation for this apparent lack of improvement in clinical management of cirrhosis is the 47% prevalence among our patients of comorbidities or complications other than those we considered in our analysis. Comorbidity has recently been demonstrated to increase both all-cause and cirrhosis-related mortality,27 and its importance is corroborated by the observation Alectinib supplier that a quarter of our patients did not die from cirrhosis, compared with 15%–20% in the older studies.3, 7 Differences in alcohol consumption also may be of importance; the proportion of abstainers in our cohort matched that in the older studies, but in those studies only complete

teetotalers counted as abstainers.3, 7 Among patients in our study, mortality increased further following the development RG7420 nmr of complications, in accordance with the existing

literature.28 Probably the higher proportion of persistent drinkers among patients with complications contributed to this association. Mortality among patients with variceal bleeding has previously been found to be similar in those with and without a history of ascites,28 but our results and those from a recent German study demonstrate that this is not the case.29 A likely explanation for the emerging importance of ascites among patients with variceal bleeding is that bleeding is less fatal now than it was in the past.30 In fact, the mortality of patients with complications was consistently lower in our study than in older studies.3, 6, 7, 10, 31 The largest earlier study, including 122 Spanish patients with alcoholic cirrhosis and 171 patients with nonalcoholic cirrhosis,11 reported that the risk of developing ascites, variceal bleeding, or hepatic encephalopathy increased steadily by 7%–10% per year in the cohort as a whole.11–14 This is consistent with our finding that 49% of patients without complications at cirrhosis diagnosis developed medchemexpress complications within 5 years. At the same time, the risk in our study was much higher during

the first year (22%) than during the following 4 years (27%, or about 7% per year). In the Spanish study, patients were not included when the clinical diagnosis was made, but when it had been confirmed by a liver biopsy in a specialist unit.11 However, patients at highest risk of complications may not have survived from clinical diagnosis to inclusion, and the risk of complications could therefore have been underestimated. Furthermore, although our study corroborates previous findings that ascites is usually the first complication to appear,11, 28 we also found a high risk of variceal bleeding or hepatic encephalopathy as the first complication. This indicates that patients with alcoholic liver cirrhosis should always be considered at risk of all three complications.

Recently, Qin et al. reported a comprehensive analysis of miRNAs in PBMCs from PBC.[37] Since we did not perform a comprehensive analysis, it is difficult to compare our results with this reported. The results reported by Qin et al. were also different from those reported by Padgett et al.,[14] who used liver tissue samples. Differences in genetic background and sample size might have also affected Abiraterone cost the results. The present target cases included those

following treatment with UDCA. We also did not analyze changes over time, meaning that the influence of treatment cannot be ruled out. We need to conduct more studies with a larger number of cases as well as examine the influence of treatment. Recent findings of abnormal expressions of specific miRNAs in various diseases are expected to lead to the development of new diagnostic biomarkers and therapeutic agents.[38] For the miRNAs

identified in the present study, more detailed investigations should be carried out to examine the relationship between their expressions and the LDK378 mw pathology of PBC. A part of this study was supported by Health Labour Sciences Research Grant from Research on Measures for Intractable Diseases, the intractable hepato-biliary disease study group in Japan. “
“UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA The cytokine tumor necrosis factor alpha (TNF-α; MCE TNF) plays a critical role early in liver regeneration following partial hepatectomy (PH). TNF stimulates at least three different pathways leading to nuclear factor kappa B (NF-κB) activation, apoptosis signaling by way of caspase-8 (Casp8), and activation of cJun N-terminal kinases (JNK). The present study aimed to better

define the role of Casp8 during liver regeneration. We performed PH in mice lacking Casp8 specifically in hepatocytes (Casp8Δhepa) and determined their liver regeneration capacity by measuring liver mass restoration and kinetics of cell cycle progression. Casp8Δhepa mice showed an accelerated onset of DNA synthesis after PH, delayed hepatocyte mitosis, but overall normal liver mass restoration. Analysis of immediate TNF-dependent signaling pathways revealed that loss of Casp8 prevents proteolytic cleavage of the receptor-interacting protein 1 (RIP1) in hepatocytes and subsequently triggers premature activation of NF-κB and JNK/cJun related signals. In order to define the role of NF-κB in this setting we blocked NF-κB activation in Casp8Δhepa mice by concomitant inactivation of the NF-κB essential modulator (NEMO) in hepatocytes. Lack of NEMO largely reverted aberrant DNA synthesis in Casp8Δhepa mice but resulted in incomplete termination of the regeneration process and hepatomegaly. Conclusion: Casp8 comprises a nonapoptotic function during liver regeneration by balancing RIP1, NF-κB, and JNK activation.

However, one isolate had cryptic chloroplasts that were difficult to observe using LM, and another had an eyespot that was so reduced as to be almost undetectable. Another isolate lacked visible chloroplasts but did possess the characteristic eyespot. Nuclear rDNA phylogenies strongly supported a monophyletic Esoptrodinium clade containing all isolates from this study together with a previous sequence from Portugal, within the Tovelliaceae. Esoptrodinium subclades were largely correlated with cytological differences, and the data suggested that independent chloroplast

and eyespot reduction and/or loss may have occurred within this taxon. Overall, the isolates encompassed the majority of cytological diversity reported in previous observations of Bernardinium/Esoptrodinium GSK1120212 clinical trial in field samples. Systematic issues with the current

taxonomic distinction between Bernardinium and Esoptrodinium are discussed. “
“The feasibility of utilizing discrete excitation-emission spectra (DEEMs) to identify dominant groups of phytoplankton at both the genus and division levels was investigated. First, the characteristics of selleck inhibitor in vivo DEEMs were extracted using Coif2 wavelet. Second, optimal characteristic spectra of scale vectors (SOCS) and time-series vectors (TOCS) were selected by Fisher linear discriminant analysis (FLDA). Third, the SOCS and TOCS were sorted using hierarchical cluster analysis (HCA), and a two-rank database was established according to their discrimination ability. Fourth, the discrimination of phytoplankton was established by nonnegative least squares (NNLS). For single-species samples, the correct identification ratios (CIRs) were 62.9%–100% at the genus level and 95.1%–100% at the division level. The dominant species in the mixtures had corresponding CIRs of 87.5% and 97.9%, and 23 dominant species were correctly identified. Prorocentrum donghaiense D. Lu, Thalassiosira nordenskioeldi Cleve, Chaetoceros socialis Lauder (bloom-forming species with a density of about 107 cell·L−1), and Skeletonema costatum (Grev.) Cleve (a dominant 上海皓元医药股份有限公司 species with a density of 104–106 cell·L−1 in seawater) were identified at the genus level. Other dominant

species in seawater were identified at the division level if their density was 105–106 cell·L−1. “
“The athecate, pseudocolonial polykrikoid dinoflag-ellates show a greater morphological complexity than many other dinoflagellate cells and contain not only elaborate extrusomes but sulci, cinguli, flagellar pairs, and nuclei in multiple copies. Among polykrikoids, Polykrikos kofoidii is a common species that plays an important role as a grazer of toxic planktonic algae but whose life cycle is poorly known. In this study, the main life cycle stages of P. kofoidii were examined and documented for the first time. The formation of gametes, 2-zooid-1-nucleus stages very different from vegetative cells, was observed and the process of gamete fusion, isogamy, was recorded.

[39] DNA hypermethylation refers principally to the gain of methylation at specific sites HSP mutation that are unmethylated under normal conditions. This aberrant methylation occurs mainly in short CpG-rich DNA stretches called “CpG islands”. DNA methylation can lead to gene silencing by either preventing or promoting the recruitment of regulatory proteins to DNA. Alternatively, it can provide binding sites for methyl-binding domain proteins, which can mediate gene repression through interactions with HDAC. This phenomenon of aberrant promoter CpG island

hypermethylation has been associated with the stabilization of transcriptional repression and loss of gene function, and occurs fundamentally in tumor suppressor genes. In contrast, DNA hypomethylation is associated mainly with the loss of DNA methylation in genome-wide regions. DNA hypomethylation has been reported in several tumor types, such as colorectal and gastric cancers. DNA hypomethylation occurs in many gene-poor genomic areas, including repetitive elements, retrotransposons and introns, where it leads to genomic instability.[40] To evaluate the significance of alterations in DNA methylation during human hepatocarcinogenesis, we have previously examined expression levels of DNA methyltransferases and DNA Crizotinib research buy methylation status in HCC. Significant overexpression of DNMT1, DNMT3A and DNMT3B was observed

in HCC compared with the corresponding MCE non-cancerous liver tissues. DNA hypermethylation on CpG

islands of p16 and methylated-in-tumor (MINT)1, 2, 12 and 31, and DNA hypomethylation on pericentromeric satellite regions satellites 2 and 3 were detected in HCC. Thus, aberrant expression of DNA methyltransferases and aberrant DNA methylation status on CpG islands and pericentromeric satellite regions play critical roles during human hepatocarcinogenesis.[41] We have also reported that the incidence of increased DNMT1 protein expression in HCC correlated significantly with poor tumor differentiation and portal vein involvement. Moreover, the recurrence-free and overall survival rates of patients with HCC exhibiting increased DNMT1 protein expression were significantly lower than those of patients with HCC that did not exhibit increased expression. Increased DNMT1 protein expression may play a critical role in the malignant progression of HCC and be a biologic predictor of both HCC recurrence and a poor prognosis in HCC patients.[42] DNMT3B is required for methylation on pericentromeric satellite regions during mouse development.[43] To clarify the molecular mechanism underlying DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis, we examined mutations of the DNMT3B gene and expression levels of splice variants of DNMT3B in HCC cases. Mutation of the DNMT3B gene was not found in HCC.

No existing animal model of alcoholic liver disease faithfully recapitulates the pathological features of advanced forms of Vemurafenib molecular weight AH; therefore, this study aimed to develop an acute-on-chronic alcoholic liver disease model by combining chronic low-dose treatment with carbon tetrachloride (CCl4) or 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) to induce hepatic fibrosis with the intragastric alcohol feeding protocol. Methods: We evaluated several study designs using C57BL6/J mice (male, 9 weeks of age). First, increasing duration of CCl4 treatment (0.2 ml/kg, 2× weekly i.p. for up to 6 weeks) were used to induce

chronic liver fibrosis. Second, feeding DDC (up to 0.1 % w/w, 4 weeks) in the diet resulted in chronic liver fibrosis and cholestasis. Alcohol (up to 27 g/ kg/day for up to 28 days) was administered intragastrically at the end of the pro-fibrogenic treatments. Results: We observed increased mortality in the experimental groups which were treated first with CCl4 for 6 weeks then administered alcohol intragastrically in combination with continuous treatment PD-0332991 ic50 with CCl4 (0.1 ml/kg, 2× week) (CCl4+CCl4+EtOH) and mice treated

with DDC diet for 4 weeks then administered alcohol intragastrically in combination with continuous treatment with DDC diet (0.05 %( w/w), 4 weeks) (DDC+DDC+EtOH). We observed increased exacerbation of liver and kidney injury only in mice of CCl4+CCl4+EtOH group. The liver and kidney histopathological evaluation, as well as other histological and molecular markers were evaluated. Conclusions: High mortality in mice with liver fibrosis that were treated with alcohol was associated with both liver and kidney injury, similar to AH in humans. The mouse models evaluated in this study reproduce features of an acute-on-chronic type clinical scenario with many features of AH. Disclosures: Ramon Bataller – Advisory Committees or Review Panels: Sandhill; Consulting: VTI The following people have nothing to disclose: MCE Shinji Furuya, Takeki Uehara, Yuki Kato, Oksana Kosyk, Gemma Odena,

Hiroshi Kono, Ivan Rusyn Purpose: 5-HT7 receptors, those central effects are well known, are also included in peripheral phenomenon. Paracetamol (PARA) has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. This study aimed to determine potential role of peripheral liver 5-HT7 receptors during PARA induced hepatotoxicity in mice. Methods: 105 mice were divided into 7 groups as each composed of 15 rats: 1) Control, 2) PARA (400 mg/kg, po), 3) PARA+ agonist 5 mg/kg (ip), 4) PARA+ agonist 10 mg/kg (ip), 5) PARA+ antagonist 10 mg/kg (ip), 6) PARA+ antagonist 20 mg/kg (ip), 7) PARA+agonist 10 mg/kg+antagonist 20 mg/ kg (ip). 5 mice per group were sacrificed in three different time points (4, 8 and 12 hours after PARA administration). Blood and tissue samples were collected.