Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced by Plasmodium berghei ANKA Infection.

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium-infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.

The visceral larva migrans caused by Toxocara canis: a case report.

Hepatic toxocarosis is caused by the dog´s roundworm, Toxocara canis. Responsible for an eosinophilic inflammatory syndrome causing liver damage that can be detected on ultrasound, computed tomography and sometimes magnetic resonance imaging. We report the case of a nine-year-old child, living in countryside, with a notion of cohabitation with canids. He presented a digestive symptomatology revealed by abdominal pain, with a hemeosinophilia in the hemogram. The etiological assessment of hyper eosinophilia objectified a positive Toxocara canisserology. The imaging assessment in search of digestive visceral lesions, found multiple heterogeneous hypoechogenic areas, poorly defined, scattered in the liver. On the abdominal CT scan, its areas appear of unenhanced density and low density and better visible after injection of contrast product. This observation reveals that imagery, although not very specific, helps in the assessment of liver damage from digestive toxocarosis.

Therapeutic effect of Moringa oleifera and Thymus vulgaris oils against hepatic coccidiosis in experimentally infected rabbits.

The present study was conducted to detect the therapeutic effect of Moringa oleifera and Thymus vulgaris oils on hepatic coccidiosis in experimentally infected rabbits. Also, immunomodulatory effect of the two oils was detected. Twenty-four Newzealand rabbits were used in this study and divided into 4 groups; healthy rabbits, experimentally infected rabbits with Eimeria stiedae oocysts, and two infected treated groups (one with moringa (200 mg/kg) and the other with thyme (500 mg/kg) oils). The results showed highly significant reduction in oocysts shedding (P<0.001 and P<0.05) in the two infected and treated rabbits than the infected non-treated rabbits in almost all days post infection (PI). Thyme oil was more potent and stopped oocysts shedding earlier at the day 34 PI compared to moringa oil at the day 41 PI. Microscopically, there was a damage in the oocysts shed by treated rabbits. Macroscopically, the livers of thyme oil treated rabbits showed more enhancement with protection percentage 75% than those treated with moringa oil in which protection percentage was 55%. The highest titer of antibodies was detected in moringa oil treated rabbits. It was concluded that both moringa and thyme oils had an anti-coccidial effect with thyme oil superiority. So, thyme oil could be useful as an alternative product for the control of rabbit coccidiosis.

Flexible 3D Cell-Based Platforms for the Discovery and Profiling of Novel Drugs Targeting Plasmodium Hepatic Infection.

The restricted pipeline of drugs targeting the liver stage of Plasmodium infection reflects the scarcity of cell models that mimic the human hepatic phenotype and drug metabolism, as well as Plasmodium hepatic infection. Using stirred-tank culture systems, spheroids of human hepatic cell lines were generated, sustaining a stable hepatic phenotype over 4 weeks of culture. Spheroids were employed in the establishment of 3D Plasmodium berghei infection platforms that relied on static or dynamic culture conditions. P. berghei invasion and development were recapitulated in the hepatic spheroids, yielding blood-infective merozoites. The translational potential of the 3D platforms was demonstrated by comparing the in vitro minimum inhibitory concentration of M5717, a compound under clinical development, with in vivo plasma concentrations that clear liver stage P. berghei in mice. Our results show that the 3D platforms are flexible and scalable and can predict the efficacy of antiplasmodial therapies, constituting a powerful tool for integration in drug discovery programs.

Toxocariasis Suspected of Having Infiltrated Directly from the Liver to the Lung through the Diaphragm.

A 37-year-old woman presented to our hospital with mild abdominal pain experienced for 2 months and hepatic nodules in segments 3 and 8. Peripheral blood eosinophilia was observed, and toxocariasis was serologically diagnosed. Seventeen days after the first imaging evaluation, a new lesion was found in segment 9 of the right lung, which was contiguous through the diaphragm to the hepatic nodule in segment 8. After treatment with albendazole, the liver and lung nodules disappeared. We suspect that larvae had directly invaded the lung from the liver, through the diaphragm.

Clinical and laboratory characterizations of hepatic capillariasis.

Hepatic capillariasis is a rare and neglected parasitic disease caused by infection with Capillaria hepatica in human liver. The disease is not well described and the information for the disease's clinical manifestation, laboratory findings and disease management strategy is not well reported. The limited information for this neglected infection often results in the delay of diagnosis or misdiagnosed to other diseases, therefore the real prevalence or severity of the infection may be underestimated. More case report with systemic analysis and features summary of this disease is needed to better understand the serious zoonotic disease. This study included systemic analysis of 16 patients infected with hepatic capillariasis in China between 2011-2017, including clinical manifestations, laboratory/radiative image findings and treatment results. Clinical manifestation included sustained fever (56.25%), respiratory disorder (37.5%), abdominal pain (37.5%), diarrhea (25%), leukocytosis (93.75%) and eosinophilia (100%). No egg was detected in feces of all patients. Over 60% patients showed elevated level of hepatic enzymes and proteins related to liver fibrosis in sera. Ultrasound and MRI examinations displayed scattered parasitic granuloma leisure in affected liver. Liver biopsy revealed parasite eggs, necrotized parasitic granulomas and septal fibrosis. Treatment with albendazole combined with corticoids for several treatment courses cured all patients with capillariasis. The difficulty of diagnosis, apparent damage of liver functions and potential fibrosis make the disease's prevalence and severity underestimated.

The polysaccharide from Inonotus obliquus protects mice from Toxoplasma gondii-induced liver injury.

The study aimed to explore the protective effects and mechanism of Inonotus obliquus polysaccharide (IOP) on liver injury caused by Toxoplasma gondii (T. gondii) infection in mice. The results showed that treatment with IOP significantly decreased the liver coefficient, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and nitric oxide (NO), and increased the contents of antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH). IOP effectively decreased the expression of serum tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ) and interluekin-4 (IL-4) in T. gondii-infected mice. In agreement with these observations, IOP also alleviated hepatic pathological damages caused by T. gondii. Furthermore, we found that IOP down-regulated the levels of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), phosphorylations of nuclear factor-κappaB (NF-κB) p65 and inhibitor kappaBα (IκBα), whereas up-regulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). These findings suggest that IOP possesses hepatoprotective effects against T. gondii-induced liver injury in mice, and such protection is at least in part due to its anti-inflammatory effects through inhibiting the TLRs/NF-κB signaling axis and the activation of an antioxidant response by inducing the Nrf2/HO-1 signaling.

Small Molecules Effective Against Liver and Blood Stage Malarial Infection.

Malaria is a lethal disease causing devastating global impact by killing more than 8,00,000 individuals yearly. A noticeable decline in malaria related deaths can be attributed to the most reliable treatment, ACTs against P. falciparum. However, the cumulative resistance of the malaria parasite against ACTs is a global threat to control the disease and, therefore the new effective therapeutics are urgently needed, including new treatment approaches. Majority of the antimalarial drugs target BS malarial infection. Currently, scientists are eager to explore the drugs with potency against not only BS but other life stages such as sexual and asexual stages of the malaria parasite. Liver Stage is considered as one of the important drug targets as it always leads to BS and the infection can be cured at this stage before it enters into the Blood Stage. However, a limited number of compounds are reported effective against LS malaria infection probably due to scarcity of in vitro LS culture methods and clinical possibilities. This mini review covers a range of chemical compounds showing efficacy against BS and LS of the malaria parasite's life cycle collectively (i.e. dual stage activity). These scaffolds targeting dual stages are essential for the eradication of malaria and to evade resistance.

Hepatic schistosomiasis with massive splenomegaly: a case report and literature review.

Schistosomiasis is a parasitic disease caused by Schistosoma species. Intestinal and hepatic schistosomiases are the most common forms of chronic disease. We describe a case of a 26-year old patient from Eritrea who was referred to our hospital with abdominal pain and diarrhea. The diagnosis of hepatosplenic schistosomiasis was made by liver biopsy and the patient was treated with praziquantel. Hepatic schistosomiasis is characterised by deposition of schistosomal eggs in the liver which results in a host cell immune response and leads to granuloma formation and neoangiogenesis. This is hallmarked by different grades of periportal fibrosis with portal hypertension leading to splenomegaly. Normal liver architecture is preserved and periportal fibrosis can be reversible if treated adequately and timely. With a recent native schistosomiasis cluster report from France and the expected influx to Europe of persons from regions endemic for schistosomiasis, increased awareness of this disease in healthcare practitioners is needed. We review the epidemiology, pathogenesis, clinical presentation and treatment of schistosomiasis.

Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.

Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196), P < 0.01. The rise in sCD14 was lower (P < 0.01) in the rifaximin group (median rise 122 ng/mL, IQR-184, 783) than in the non-rifaximin group (median rise 832 ng/mL, IQR 530, 967). TNFR1 decreased (P < 0.01) in the rifaximin group (median -39 ng/mL IQR-306, 563) but increased in the non-rifaximin group (median 166 ng/mL, IQR 3, 337). Other markers remained unaffected. Rifaximin led to a reduction of inflammatory markers and bacterial 16S rRNA which may implicate BT in the inflammation in HSS.

Hepatic Paragonimiasis Mimicking Hepatocellular Carcinoma.

Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus Paragonimus. Ectopic infection may occur but rarely involves the liver. Here, we report a case of hepatic paragonimiasis in a Chinese man who was initially suspected to have hepatocellular carcinoma. He had been previously diagnosed with chronic hepatitis B. No specific symptoms or abnormal blood test results were observed, except for a significant rise in serum alfa-fetoprotein. Magnetic resonance imaging revealed a 12-cm mass with inhomogeneous signal intensity at the left lobe of the liver. Laparoscopic left hemihepatectomy was performed. He was finally diagnosed as hepatic paragonimiasis upon pathological examination and antibody serology. The postoperative course was uneventful. He received a standard course of praziquantel and recovered well. Our case is unique in its tumor-like characteristic and protrudes the difficulty of differential diagnosis with both benignant and malignant hepatic diseases by imaging studies or non-specific symptoms. Hepatic paragonimiasis is unusual; however, it should be considered in the differential diagnosis of liver malignancy by clinicians.

Hepatosplenic schistosomiasis: playing hide-and-seek with an elusive parasite.

A 27-year-old man of Eritrean origin presented with persistent left-sided abdominal pain. Initial investigation showed signs of liver fibrosis, portal hypertension and splenomegaly. A diagnosis of hepatosplenic schistosomiasis was suspected on grounds of elevated total IgE, grey area antischistosomiasis antibodies and the high endemic status of his native country. However, repeated microscopy of faecal and urine samples, as well as rectal biopsies, failed to demonstrate schistosomal eggs. Finally, the diagnosis of hepatosplenic schistosomiasis was established through demonstration of a Schistosoma mansoni egg in a liver biopsy taken in an attempt to clarify the cause of the above findings. The patient had recently been treated for uncomplicated malaria. Lowered schistosomiasis worm/egg burden and hence reduced sensitivity of classic microscopy-based schistosomiasis testing was attributed to the antischistosomal activity of the antimalarial chemotherapy.

DIAGNOSIS AND THERAPY OF LIVER FLUKE (FASCIOLOIDES MAGNA) INFECTION IN FALLOW DEER (DAMA DAMA) IN SERBIA.

Giant liver fluke ( Fascioloides magna ) infection is an important health problem of cervids in southeastern Europe. We measured the prevalence and intensity of infection with F. magna in a fenced area near the Danube River in the South Backa District of Serbia. Parasitologic, pathomorphologic, and histopathologic examinations were conducted from November 2007 to February 2008, beginning with a population of 127 adult fallow deer ( Dama dama ). After a positive diagnosis, therapy with triclabendazole-medicated corn was applied. Deer were treated at four baiting stations, using medicated feed providing triclabendazole at an estimated dose of 10-14 mg/kg of body weight per deer. Treatment lasted for 7 d in early February 2008 and an additional 7 d 2 wk later. For the complete success of pharmacotherapy it was necessary to prevent any contact of deer with the snail intermediate host ( Galba truncatula ). Intervention in the habitat, removing grass and low vegetation, and draining ponds reduces the possibility of contact. Six months after the treatment, livers of hunted deer were reddish, with fibrous tracks; pigmentation and cysts in the parenchyma were surrounded by a fibrous capsule and their fecal samples contained no eggs of F. magna . Over the following years, livers of hunted deer were negative, and the last control cull in March 2015 confirmed complete absence of infection. We reconfirmed the presence of giant liver flukes in fallow deer in Serbia, apparently the result of natural spread across the Danube from Hungary and Croatia. We also report that the treatment of deer with triclabendazole-medicated corn is an effective method for administration of therapeutic doses of drug in semicaptive deer. Interventions in the environment are necessary to prevent recontact of deer with habitats used by the snail intermediate host, and enable the success of the therapy.

HEPATOPROTECTIVE ROLE OF PLACENTA HYDROLISAT - LAENNEC IN THE TREATMENT OF PATIENTS WITH VIRAL AND PARASITIC LIVER DISEASES.

The article presents data on non-alcoholic fatty liver disease and chronic viral hepatitis C in combination with opisthorchosis invasion. With the system approach considers the specific features of the clinical, laboratory and functional data in patients with combined pathology. Observed frequency of the pain, asthenic and allergic cholestatic syndromes, the latter as part of the triad Paltsev. The high efficiency of the placenta hydrolisat - laennec, as means of pathogenetic therapy.

IFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.

In C57BL/6 mice, Leishmania donovani infection in the liver provoked IFN-γ-induced expression of the immunity-related GTPases (IRG), Irgm1 and Irgm3. To gauge the antileishmanial effects of these macrophage factors in the liver, intracellular infection was analyzed in IRG-deficient mice. In early- (but not late-) stage infection, Irgm3(-/-) mice failed to properly control parasite replication, generated little tissue inflammation and were hyporesponsive to pentavalent antimony (Sb) chemotherapy. Observations limited to early-stage infection in Irgm1(-/-) mice demonstrated increased susceptibility and virtually no inflammatory cell recruitment to heavily-parasitized parenchymal foci but an intact response to chemotherapy. In L. donovani infection in the liver, the absence of either Irgm1 or Irgm3 impairs early inflammation and initial resistance; the absence of Irgm3, but not Irgm1, also appears to impair the intracellular efficacy of Sb chemotherapy.

Significance of Charcot Leyden crystals in liver cytology-A case report.

Charcot Leyden crystals are colorless, hexagonal, bipyramidal crystals formed from aggregation of material from disintegrating eosinophils. Eosinophilic infiltrate along with the presence of Charcot Leyden crystals is an indirect evidence of parasitic infestation. Here, we report a case where fine-needle aspiration cytology smears prepared from hepatic space occupying lesion showed numerous Charcot Leyden crystals along with eosinophilic infiltrate, indicating parasitic infection.

Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice.

BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER), an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i) by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii) by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii) by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv) by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

Hepatic cysticercosis: a rare entity.

Hepatic cysticercosis is a very rare entity; only four cases have been reported to date. High-resolution ultrasonography of the abdomen is the initial and most reliable modality for evaluation of hepatic cysticercosis. Medical therapy is the mainstay of treatment. We report a case of hepatic cysticercosis in a 28-year-old male who presented with right upper quadrant pain, fever, and jaundice. The article also describes the imaging patterns of hepatic cysticercosis based on different stages of evolution.