Liver Cell Necrosis Research Articles

Antioxidative and Hepatoprotective Effects of Physalis peruviana Extract against Acetaminophen-Induced Liver Injury in Rats

The aim of this study was to examine the antioxidant activities of Physalis peruviana L. (Solanaceae) aqueous extract (PPWE) and its protective effect against acetaminophen (APAP)-induced hepatotoxicity in rats. Using different models of antioxidant assay, namely ferric thiocyanate, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power, PPWE showed a dose-dependent increase in antioxidant activities, with total antioxidant activity (IC50: 0.81 μ g/ml) close to that of vitamin C (IC50: 0.89 μ g/ml). APAP at 850 mg/kg significantly increased the levels of serum glutamic pyruvic transaminase (sGPT), glutamic oxaloacetic transaminase (sGOT) and alkaline phosphatase (sALP). However, pre-treatment with PPWE at doses 150, 300, and 600 mg/kg body weight significantly prevented the increase in these enzymes, which are the major indicators of liver hepatitis. Biochemical assays of liver homogenate showed that PPWE at 150∼ 600 mg/kg significantly enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) concentrations, and diminished the level of thiobarbituric acid reactive substances (TBARS). Furthermore, liver histological observation also showed an obvious amelioration in the liver cell necrosis, liver lesion, and fatty changes in PP-treated groups. High performance liquid chromatographic analysis showed that ellagic acid (ca. 0.2%) but not others could be the major component contributing to the antioxidant and hepatoprotective activities of PPWE. The present study concludes that PPWE possesses antioxidant activity and potent hepatoprotective effect against APAP-induced liver injury in rats.

Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.

Acute hepatitis in a patient with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary syndrome characterized by recurrent episodes of fever and serositis. In this report, we describe a Japanese patient with FMF and Sjögren's syndrome, in whom acute elevations of transaminase occurred. The histological findings from the liver biopsy specimens demonstrated a nonspecific hepatitis, with liver cell necrosis and interlobular inflammatory cell invasion, without the presence of interface hepatitis or bile duct injury. This case underscores the possibility that MEFV mutations contribute to hepatic inflammation, as seen in this case, by way of an alteration of the pyrin function.

Toxicity and anthelmintic efficacy of crude aqueous of extract of the bark of Sacoglottis gabonensis

The water extract of the stem bark of Sacoglottis gabonensis was evaluated for its preliminary acute toxicity and anthelmintic efficacy against gastro-intestinal nematodes of small ruminants and mice in both in vitro and in vivo studies. Intra-peritoneal administration of doses ranging from 400 to 3200 mg/kg of the aqueous stem bark extract produced varying degrees of toxicity manifested as depression, drowsiness and unsteady gait, paralysis of the hind limbs, dyspnoea, coma and death. The pathological lesions noted at necropsy were mainly congestion and edema of the lungs, bronchi and bronchioles and hepatomegally with focal necrosis of liver cells. The severity of the clinical symptoms and pathological lesions were dose-related. In the in vitro study, the extract significantly ( P < 0.05) reduced the hatching of strongyline nematode eggs from naturally infected small ruminants. The 100 mg/ml concentration of the extract produced the highest (94.4%) inhibition on nematode egg hatch and the result was comparable to similar effect produced by either levamisole (100% at 15 mg/ml) or albendazole (99.7% at 6.25 mg/ml). In rats experimentally infected with Heligmosomoides polygyrus, treatment with the S. gabonensis stem bark aqueous extract significantly ( P < 0.05) reduced adult worm burden and completely inhibited faecal egg output 5 days post treatment.

Purification, characterization and potent lung lesion activity of an l-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom

l-amino acid oxidases (LAOs) are one of the major components of snake venoms, which possess numerous biological functions. However, little is known of the influence of LAOs on organ lesions. In the present study, a unique LAO from Agkistrodon blomhoffii ussurensis snake venom named ABU-LAO was purified by Heparin-Sepharose FF chromatography followed by an ion-exchange chromatography procedure. The purified ABU-LAO appears a dimer with a molecular mass of approximately 108.8 kDa. Kinetics studies showed that ABU-LAO is very active towards its substrates l-Asn, l-Phe, l-Tyr, l-Leu, l-Ile and l-Trp. The most striking observation in the present study is that ABU-LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. ABU-LAO also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. In conclusion, ABU-LAO potently induces lesions in lungs and livers. The ability of ABU-LAO will contribute to the understanding of the pathogenesis of snakebite wound.

Pacheco’s disease in a Hungarian zoo bird population: A case report

An epizootic of Pacheco's disease is reported from a zoo bird population. The infection was introduced by wild-captured Patagonian conures (Cyanoliseus patagonus) despite 61 days of quarantine. The disease affected several parrot species and, interestingly, three out of seven bearded barbets (Lybius dubius). The mortality rate was 30.93%. Autopsy revealed abdominal hyperaemia with liver haemorrhages and, in less rapid cases, yellowish discoloration and fragility of the liver. Death was caused by the collapse of circulation. Histopathology demonstrated liver cell necrosis, disintegration of the lobular structure, and a few intranuclear inclusion bodies. Icosahedral virions were detected by electron microscopy. The virus was isolated in the allantoic cavity of embryonated chicken eggs as well as in chicken embryo fibroblast cell culture. A 281-bp-long fragment of psittacid herpesvirus DNA was detected by PCR in cell culture material and liver samples of the affected birds. To our knowledge this is the first report of Pacheco's disease in bearded barbets as well as the first occurrence of Pacheco's disease in Hungary.

Pericentral Liver Cell Necrosis Associated with the Use of High-Dose Intravenous Methylprednisolone

Pericentral Liver Cell Necrosis Associated with the Use of High-Dose Intravenous Methylprednisolone

Immunological response in alcoholic liver disease

The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD.

Alcoholic liver disease

Alcohol excess is associated with a spectrum of disease ranging from simple steatosis through steatohepatitis to cirrhosis and, in some, hepatocellular carcinoma. Alcoholic steatohepatitis itself has a variable histological picture, but a constant feature is the presence of ballooning degeneration of hepatocytes. Recent studies have emphasized the importance of apoptosis as a mechanism of cell death in this condition. It is accompanied by varying degrees of perivenular, centrilobular, and pericellular fibrosis. When severe and associated with perivenular liver cell necrosis (central sclerosing hyaline necrosis), there may be precirrhotic portal hypertension. The pattern of fibrosis may initially be diffuse with little nodule formation, but in time there is frequently the development of a micronodular cirrhosis. In approximately 15% of patients with established cirrhosis, hepatocellular carcinoma develops; several precursor lesions are now recognized which can be detected histologically. Several authors have drawn attention to additional components of the spectrum of alcoholic liver disease, including vascular changes, portal tract inflammation and fibrosis, ductular reaction, and iron overload. The morphology of alcoholic liver disease can be significantly affected by abstinence; furthermore, the clinical and morphological phenotype can be significantly influenced by the presence of comorbid conditions such as nonalcoholic fatty liver disease or viral hepatitis. Biopsy appearances can provide important prognostic information in alcoholic liver disease, and this review incorporates a proposed grading and staging schema for assessment of histological severity.

Efeitos da oxigenoterapia hiperbárica em ratos submetidos à ligadura das veias hepáticas: avaliação da mortalidade e da histologia do fígado e baço

To evaluate the effects of hyperbaric oxygen therapy in rats submitted to instantaneously hepatic vein obstruction. 30 Holtzman adult male rats were utilised, distributed into two groups: 1) hepatic vein obstruction; 2) hepatic vein obstruction associated with hyperbaric oxygen therapy. General anaesthesia was utilized by a solution composed of ketamine chloride (40 mg/ml) and meperidine chloride (10 mg/ml) in a dose of 50/mg/weight, applied into the right gluteus muscle. The animals belonged to group 2 were submitted to hyperbaric oxygen therapy, 8 hours after the operations, in a 2,5 atmosphere, which lasts 120 minutes per day, in consecutive 20 days. The statistical analysis was made in relation to mortality and histological study of livers and spleens utilizing the Fisher test, and the results were considered statistically significant when p < 0.05. Occurred seven (46.67%) deaths between animals belonged to group 1 and no deaths in the animals belonged to group 2. The histological studies made in the livers and spleens of the animals belonged to group 1 showed many alterations in the following percentages: thrombosis of hepatic, portal and center-lobular veins in five (33.3%), very extensive necrosis of liver cells in seven (46.7%), and light in eight (53.3%), Kupffer cells developed and hypertrophied in 14 (93.3%), high congestion of the spleen purple in six (40.0%) and moderate and severe hemossiderinosis spleen in 14 (93.3%). The analysis of this parameters in the group 2 only showed light necrosis of liver cells, Kupffer cells light developed and hypertrophied, moderated congestion of the spleen purple and light hemossiderinosis spleen. All these parameters analysed showed significantly difference (p < 0.05) between these two groups. It could be concluded that the hyperbaric oxygen therapy applied in rats, with instantaneously hepatic vein obstruction decreased their post-surgical mortality and their early deleterious effects in the liver and spleen.

함초의 간독성에 대한 보호효과

본 연구는 함초 물추출물을 2주간 투여 해 온 횐쥐에 <TEX>$CCl_4$</TEX> 투여로 인한 간독성 발현 정도를 조사하기 위해 수행되었다. SD-Rat를 2주 동안 함초 추출물 100 mg/kg이 되도록 복강내에 투여한 다음날인 15일째, <TEX>$CCl_4$</TEX>를 투여하고 12시간 후에 에테르 마취 후 간과 혈청을 분리하여 측정하였다. AST, ALT는 대조군에 비해서 함초 투여군이 <TEX>$65.56\%$</TEX>와 <TEX>$59.04\%$</TEX>로 억제 되었다. MDA수치는 대조군과 비교해서 함초 투여군의 간 homogenate에서 <TEX>$53.74\%$</TEX> 억제되었고, 미토콘드리아에서는 <TEX>$89.86\%$</TEX>억제되었다. SOD의 활성은 대조군과 비교해서 함초 투여군의 간 homogenate에서 <TEX>$42.51\%$</TEX>억제되었고, 미토콘드리아에서는 <TEX>$38.42\%$</TEX>억제 되었다. 조직 실험 결과 <TEX>$CCl_4$</TEX>으로 나타난 간세포의 괴사와 울혈이 함초 투여군에서는 조직실험 결과 감소되는 것으로 나타났다. 모든 데이터는 <TEX>$CCl_4$</TEX>로 유도된 간독성을 함초 추출물이 보호하는 결과를 보였으며, 이는 간독성에 대한 보호효과를 가진 약물 소재 개발에 이용될 수 있다고 본다. This study was carried out to investigate the effects of Salicornia herbacea L. (SH) on carbon tetrachloride <TEX>$(CCl_4)-induced$</TEX> hepatotoxicity. Sprague-Dawley rats were intraperitoneally administered the SH at 100 mg/kg per day for two weeks. Then single dose of <TEX>$CCl_4$</TEX> (3.3 ml/kg) was injected into rats. Twelve hours later, they were anesthesized with ether and dissected. <TEX>$SH-CCl_4-administered$</TEX> group showed <TEX>$65.56\%\;and\;59.04\%$</TEX> of inhibitory effects in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, compared to <TEX>$CCl_4-treated$</TEX> group (p<0.05). Malonedialdehyde (MDA) levels of <TEX>$SH-CCl_4-administered$</TEX> group in liver homogenate and mitochondria were significantly inhibited by <TEX>$53.74\%,\;89.86\%$</TEX>, and respectively, compared to <TEX>$CCl_4-treated$</TEX> group (p<0.05). Superoxide dismutase (SOD) activities of <TEX>$SH-CCl_4-administered$</TEX> group in liver homogenate and mitochondria were significantly inhibited by <TEX>$42.51\%,\;and\;38.42\%$</TEX>, respectively, compared to <TEX>$CCl_4-treated$</TEX> group (p<0.05). The histological examinations showed that the liver cell necrosis and centrilobular congestive aggregation induced by <TEX>$CCl_4$</TEX> were clearly eliminated by the administration of SH. These results suggest that SH could have the protective effects against hepatotoxicity.

Fatal Venlafaxine Overdose With Acinar Zone 3 Liver Cell Necrosis

We present a case of fatal venlafaxine overdose in a 34-year-old male with a history of depression and previous suicide attempts. He presented unwell, and his condition deteriorated with the development of rhabdomyocytolysis and renal failure. Although treatment was provided, this was unsuccessful, and he died within a day of his admission. A postmortem examination was performed, and the findings included an acinar zone 3 pattern of liver cell necrosis and a very high level of serum venlafaxine in the deceased. No other elevated drug levels were detected. From this case, it is clear that venlafaxine overdose was the primary cause of a fatal acinar zone 3 pattern of liver cell necrosis. As far as we are aware, this is the first reported case of fatal acinar zone 3 liver necrosis caused by venlafaxine overdose alone.

Effect and mechanisms of FR167653, a dual inhibitor of TNF-α and IL-1, on BCG plus LPS induced-liver injury

To investigate the effect of FR167653, a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), on Bacillus Calmétte-Guérin (BCG) plus lipopolysaccharide (LPS) induced-liver injury and its mechanisms. Mouse liver injury was established by tail vein injection of 2.5 mg BCG, and 10 d later with 10 microg LPS. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed by spectrophotometry. Liver samples were stained with hematoxylin and eosin. Rat hepatocytes (HCs) and Kupffer cells (KCs) were isolated by collagenase IV and pronase perfusion, and purified by density gradient separation. TNF-alpha and IL-1 concentrations were measured with ELISA. TNF-alpha and IL-1 mRNA in KCs was analyzed with RT-PCR. FR167653 significantly decreased the elevated transaminase (ALT, AST) activity in serum of liver injured mice. Meanwhile, the degree of inflammatory cell infiltration and liver cell necrosis was also ameliorated. TNF-alpha and IL-1 production by KCs stimulated with LPS was significantly inhibited by FR167653. RT-PCR analysis demonstrated that FR167653 also reduced the augmented expression of TNF-alpha and IL-1 mRNA in KCs. However, FR167653 up to 10 micromol/L did not have a toxic effect on KC viability. In addition, FR167653 alleviated the HC injury induced by LPS pre-treated Kupffer cell-conditioned medium (KCCM). Addition of anti-IL-1 and anti-TNF-alpha MAbs significantly decreased the ALT level released from HCs incubated with LPS or FR167653 pre-treated KCCM. TNF-alpha and IL-1 released from activated KCs were involved in BCG plus LPS induced liver injury. FR167653 significantly attenuated hepatocyte injury via inhibition of TNF-alpha and IL-1 released from activated KCs.

The Liver and Hemorrhagic Shock

l c t i t z i U o t l r p g a d c t r istorical perspective lthough anecdotal reports of liver trauma such as that f Hellwig and Orr alluded to the effect of shock on the iver, the first large clinical review of liver ischemia was ublished by Bywaters in 1946. Forty-two patients dyng from blunt trauma were presented and autopsy maerial was examined. Twenty-seven (64%) patients in his group were hypotensive, as defined in this study by systolic blood pressure less than 90 mmHg, from 1 to ore than 10 hours. Histologically, some degree of liver ecrosis was found in eight of these patients, particularly n those with more prolonged periods of shock. The attern of necrosis was noted to be midzonal or paracenral, sparing the periportal and, many times, the central egions of the lobule. The earliest necrotic changes were een as soon as 24 hours after injury. Bywaters concluded hat the most likely explanation for this phenomenon as liver anoxia from hemorrhagic shock. The role of hock in production of hepatocyte necrosis was eluciated by Ellenberg and Osserman in 1951. Of 34 paients with central liver cell necrosis, 32 (94%) were ssociated with shock. Again, the duration of shock eemed to be a principal determinant of the presence of ecrosis. The midzonal pattern of cell damage, however, as not as clearly seen. Preexisting conditions, such as irrhosis, in many of the patients might have resulted in ore extensive lobular injury than was seen by others. In 967, Kantrowitz and coauthors published a detailed linicopathologic analysis of four patients suffering arked liver impairment after hemorrhagic shock. Hyerbilirubinemia began early, around the third or fourth ostoperative day, and progressed to profound degrees, p to 39 mg/dL by postoperative days 9 to 18. This was ssociated with elevations of alkaline phosphatase, hich gave the impression of cholestatic jaundice de-

A Case of Neonatal Hemochromatosis‐Like Liver Failure with Spontaneous Remission

A Case of Neonatal Hemochromatosis‐Like Liver Failure with Spontaneous Remission

Formes pauci-symptomatiques du syndrome respiratoire aigu sévère (sras)

IntroductionUne épidémie de pneumopathies atypiques est apparue en novembre 2002 dans la région Chinoise de Guangdong. Elle a ensuite été décrite sous le nom de syndrome respiratoire aigu sévère (SRAS) à partir de nouveaux foyers survenus à Hanoi et à Hong Kong en février 2003. En France, 5 cas reliés au même patient source ont été rapportés.ObservationNous rapportons l’observation d’un patient de 52 ans contact direct avec un cas probable de SRAS. À l’admission, le patient présente une hyperthermie isolée sans symptomatologie respiratoire associée à une lymphopénie et une cytolyse hépatique. La radiographie thoracique est normale. La tomodensitométrie thoracique objective l’existence d’un aspect en verre dépoli sous pleural. L’étude par PCR des prélèvements naso-pharyngés précoces (36e heure) à la recherche du coronavirus associé au SARS sera négative. La confirmation du cas sera obtenue par l’étude sérologique.ConclusionsCette observation illustre l’existence de présentations cliniques frustres du syndrome respiratoire aigu sévère. La contagiosité des formes pauci symptomatiques n’est pas connue. Des analyses sérologiques permettront de mieux les préciser. Le danger actuel d’une recrudescence saisonnière particulièrement hivernale ne peut être écarté. Dans ce contexte, l’existence et la reconnaissance des formes pauci symptomatiques pour lesquelles la contagiosité ne peut être écartée est primordiale.

Pathophysiological Role of Poly(ADP-Ribose) Polymerase (PARP) Activation during Acetaminophen-Induced Liver Cell Necrosis in Mice

DNA fragmentation in hepatocytes occurs early after acetaminophen (AAP) overdose in mice. DNA strandbreaks can induce excessive activation of poly(ADP-ribose) polymerases (PARP), which may lead to oncotic necrosis. Based on controversial findings with chemical PARP inhibitors, the role of PARP-1 activation in AAP hepatotoxicity remains unclear. To investigate PARP-1 activation and evaluate a pathophysiological role of PARP-1, we used both PARP inhibitors (3-aminobenzamide; 5-aminoisoquinolinone) and PARP gene knockout mice (PARP-/-). Treatment of C3Heb/FeJ mice with 300 mg/kg AAP resulted in DNA fragmentation and alanine aminotransferase (ALT) release as early as 3 h, with further increase of these parameters up to 12 h. Few nuclei of hepatocytes stained positive for poly-ADP-ribosylated nuclear proteins (PAR) as indicator for PARP-1 activation at 4.5 h. However, the number of PAR-positive cells and staining intensity increased substantially at 6 and 12 h. Pretreatment with 500 mg/kg 3-aminobenzamide before AAP attenuated hepatic glutathione depletion and completely eliminated DNA fragmentation and liver injury. Delayed treatment several hours after AAP was still partially protective. On the other hand, liver injury was not attenuated in PARP-/- mice compared to wild-type animals. Similarly, the specific PARP-1 inhibitor 5-aminoisoquinolinone (5 mg/kg) was not protective. However, 3-aminobenzamide attenuated liver injury in WT and PARP-/- mice. In summary, PARP-1 activation is a consequence of DNA fragmentation after AAP overdose. However, PARP-1 activation is not a relevant event for AAP-induced oncotic necrosis. The protection of 3-aminobenzamide against AAP-induced liver injury was due to reduced metabolic activation and potentially its antioxidant effect but independent of PARP-1 inhibition.

Adenoviral gene transfer of ABIN‐1 protects mice from TNF/galactosamine‐induced acute liver failure and lethality†

Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a central role in acute and chronic hepatitis B and C infection and alcoholic liver disease as well as fulminant liver failure. TNF-induced liver failure is characterized by parenchymal cell apoptosis and inflammation leading to liver cell necrosis. The transcription factor NF-kappaB is believed to mediate at least part of the proinflammatory effects of TNF, and is therefore a favorite drug target. However, NF-kappaB also suppresses TNF-mediated hepatocyte apoptosis, implicating a potential cytotoxic effect of NF-kappaB inhibitors in the liver. This dual function of NF-kappaB emphasizes the need for therapeutics that can inhibit both TNF-induced NF-kappaB activation and cell death. Here we describe that adenoviral expression of the NF-kappaB inhibitory protein ABIN-1, but not an IkappaBalpha superrepressor (IkappaBalpha(s)), completely prevents lethality in the TNF/D-(+)-galactosamine-induced model of liver failure. Protection was associated with a significant decrease in TNF-induced leukocyte infiltration as well as hepatocyte apoptosis. The differential effects of ABIN-1 and IkappaBalpha(s) suggest a role for an NF-kappaB independent function of ABIN-1. Indeed, ABIN-1 was found to prevent not only NF-kappaB activation, but also apoptosis of cultured hepatocytes in response to TNF, explaining its protective effect against TNF-induced liver failure. In conclusion, ABIN-1 has a dual NF-kappaB inhibitory and anti-apoptotic activity in the liver, which might be of considerable interest for the treatment of inflammatory liver diseases.

Hepatobiliary changes, antibody response, and alteration of liver enzymes in hamsters re-infected with Opisthorchis viverrini

We investigated pathological changes, antibody response, and liver enzymes in hamsters re-infected with Opisthorchis viverrini. Group 1 received a single dose of 50 metacercariae; Groups 2 and 3 were first dosed with of 30 metacercariae and re-infected with 20 more once or twice at three month intervals. Inflammation and liver cell necrosis were observed on 3D (day 3) for Group 3 and 7D for Group 2 in comparison with 21D for Group 1. Pathological changes included peri-ductal fibrosis, bile duct dilation, and small bile duct formation. Increased O. viverrini-specific IgG levels ranked in the order Group 3 > Group 2 > Group 1. Liver enzyme activity was related to inflammatory cell infiltration. Re-infection induced faster inflammation and more severe pathological changes in association with parasite-specific antibody during chronic inflammation. This study emphasizes that there is an important relationship between the gradual decreases of inflammation with a concomitant increase in fibrosis after re-infection.

Biliary intervention augments chemotactic reaction and aggravates cholestatic liver injury in rats

Background Intervention of the biliary system is frequently done in patients with obstructive jaundice and is associated with significant morbidity and mortality. The pathogenesis is unknown. Materials and methods A rat model of bile duct ligation (BDL) for 2 weeks was established in which biliary intervention was feasible by injection of normal saline through an indwelling catheter in the bile ducts. Plasma levels of C-C chemokine MCP-1 and C-X-C chemokine MIP-2 were measured by using ELISA. Blood monocytes, Kupffer cells, and neutrophils in the liver were characterized with antibodies to ED1, ED2, and myeloperoxidase (MPO). Lipid peroxidation was measured by malondialdehyde contents and apoptosis by TUNEL stain of the liver. Results Biliary intervention resulted in an increase of plasma MCP-1 and MIP-2 proteins by 1 h, which declined to normal level by 3 h in both sham and BDL rats. The levels in BDL rats were significantly higher than in sham at most points. There was a transient increase of ED1- and ED2-positive cells and MPO-staining cells in sham rat liver by 1 h after intervention. ED2-positive cells increased significantly by 1 h, while ED1- and MPO-positive cells decreased, yet insignificantly after intervention in BDL rats. The cell counts in BDL were constantly higher than in sham. Malondialdehyde increased precipitously in BDL by 3 h and was significantly higher than in sham throughout the study period. Parenchymal liver injury, manifested by elevated ALT, as well as apoptosis and necrosis of liver cells, was significantly increased in BDL rats, but not in sham rats. Conclusion Biliary intervention augments chemokine expression, precipitates lipid peroxidation, and aggravates liver injury in cholestatic rats.