Evaluation of the hepatoprotective and antioxidant effects of Tegillarca granosa flesh body extract against potassium bromide toxicity via targeting the histomorphometry,chromosomal and expressions of TGF-β1,VEGF and COX-2 genes in rats

The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(T.granosa)flesh body extract.Twenty adult male albino rats were equally distributed into four groups;Group(I)treated with physiological saline(control group),Group(II)was orally gavaged by 200 mg/kg of T.granosa body extract day after day,Group(III)was intoxicated by KBr(150 mg/kg bwt day after day orally)and finally,Group(IV)was given a combination of T.granosa flesh body extract plus KBr with similar doses in the second and third groups.At the end of one month,blood,liver tissue and bone marrow samples were collected to be used for the required laboratory examinations.In response to KBr toxicity,there was a significant increase in serum antioxidant biomarkers,which was accompanied by a significant change in hepatocyte ultrastructure and a significant change in carbohydrate and protein levels within the liver organ.In addition,KBr intoxication resulted in a substantial increase in the incidence of chromosomal aberrations such as holes,splits,deletions,fragments,ploidy,and ring chromosomes,as well as significant upregulation of TGF-1,VEGF,and COX-2 gene expression.The hepatotoxic effect of KBr was counteracted by treatment with T.granosa flesh body extract.T.granosa flesh body extract has a curative antioxidant and numerous protective effects against KBr hepatotoxicity.

Hepatotoxicity Induced by High Dose of Methylprednisolone Therapy in a Patient with Multiple Sclerosis: A Case Report and Brief Review of Literature

Toxic hepatitis due to drugs is an important and frequent drug adverse reaction in clinical practice. Here, we report a case of high dose methylprednisolone-induced acute hepatitis in a 51-year-old woman that suffers from multiple sclerosis while steroids are usually safe drugs with regards to liver injury and even they are the treatment choice of autoimmune hepatitis, but the literatures about corticosteroids showed are not entirely safe to liver injury and they have occasionally linked to hepatotoxicity. Although recent reports have demonstrated that prednisolone may cause hepatitis. This case report includes a brief review of the relevant literature on corticosteroids-induced hepatitis that is presented.

Updated Review on the Panorama of Liver Diseases in Benin

Introduction: The aim of this work was to take stock of the epidemiological aspects of liver diseases in Benin. Methods: Two methods were used: documentary research and collection of the position of gastroenterologists on the subject. For the literature search, the sources interviewed were Medline, African Journal On Line (AJOL), Google and Google scholar. Additional searches were made on the websites of European gastroenterology societies (AFEF, EASL). A collection of the opinions of gastroenterologists, most of them members of the Beninese Society of Hepato-gastroenterology was made. Results: From a nosological point of view, the most frequent and serious liver diseases in Benin are mainly infectious: viral hepatitis B and C (9.9% and 4.12% of the general population in 2013). Bacterial liver diseases (ascites fluid infections and tuberculosis of the liver) come in 3rd position after cirrhosis and hepatocellular carcinoma. Amoebic abscesses of the liver tend to regress. The toxic causes are dominated, in addition to alcoholic liver diseases (steatosis, cirrhosis), by drug lesions: two fatal cases of hepatotoxicity by artesunate-amodiaquine combination and asymptomatic and transient cytolysis in 23.8% of 63 children less than 5 years old treated with arthemether-lumefantrine combination have been described. Phytotherapy, alone or in combination with modern drugs, can in some cases be hepatotoxic. Plants with recognized medicinal virtues (may be harmful to the liver (Senna, Moringa oleifera, tamarind). Chronic aflatoxicoses secondary to the consumption of contaminated food (maize, cassava or peanuts) are relatively under-documented. Overload diseases (in particular alcoholic or non-alcoholic fatty liver) are on the increase (3.19% of 662 ultrasounds in 1995 against 14.5% of 411 in 2011 in Cotonou) partly due to the demographic and nutritional transition underway in Benin. These diseases, often blamed on spells cast, lead to hospital deaths from cirrhosis or hepatocellular carcinoma in young economically active subjects. Conclusion: Despite anti-infectious therapeutic advances, the prevention of toxic and metabolic hepatopathies is essential. Clinical research is crucial.

Aqueous Leaves Extract of Gongronema latifolium (Benth) Downregulates the Expression of IFN-γ, IL-10 and Cell Surface Markers in Rabbits

Background: The pathophysiology of the inflammatory process reveals intricate signaling which includes the IL-1β, IL-6, and TNFα pathways that could serve as drug targets. Aim: This study determined the effect of the aqueous extract of Gongronema latifolium (AEGL) leaves on the expression of IFNγ, IL-10, CD3, and CD56 in rabbits. Materials and Methods: ELISA tests were performed to determine the effect of the AEGL on the expression of a pro-inflammatory cytokine (IFNγ), an anti-inflammatory cytokine (IL-10), and CD3 and CD56 cell surface markers in rabbits. Twenty cross-bred male rabbits with an average weight range of 1.0 - 1.5 kg were selected. The rabbits were separated into four groups of four rabbits each treated as follows: Grp1 is the untreated control;Grp2 is the treated control;and Grp3, Grp4, and Grp5 were treated with 200, 400, and 600 mg/kg of AEGL respectively for 28 days. Results: The AEGL showed its greatest inhibitory effect in Group 4 on IL-10 (118.5 pg/ml), and IFNγ (332 pg/ml) on days 14 and 21 respectively. AEGL also showed the highest inhibition of CD3 expression on days 14 and 21 (0 pg/ml) in Group 3;and CD56 expression on day 21 (630.5 pg/ml) in Group 4. Conclusion: AEGL showed exhibited strong T cell mediated anti- inflammatory, and immunomodulatory activity in test rabbits within the 28-day period which can be confirmed by cell based assays. Specifically at 400 mg/kg, AEGL exhibited the greatest anti-inflammatory activity which is suggestive of its maximum effective dose.

Hepatoprotective effects of S-adenosyl-L-methionine against alcohol-and cytochrome P450 2E1-induced liver injury

S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the naïve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected to open a new way of developing various specific therapeutics based on the high plasticity and responsiveness of MSCs.

Biopsy-confirmed fenofibrate-induced severe jaundice:A case report

BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic injury(hepatocellular or cholestatic).This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease.We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARY A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test.Abdominal ultrasound and computed tomography showed no biliary obstruction or nonspecific findings in the liver.Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis.Following the biopsy,steroid therapy was initiated and after 3 wk of treatment,the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSION In patients with hyperlipidemia,treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis,warranting clinical attention.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Antitumor and off-target effects of cholesterol-conjugated let-7a mimics in an orthotopic hepatocellular carcinoma xenograft nude mouse model

Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration ofChol-let-7a andChol-miRCtrl in the kidney and the bladder decreased much slowly in the xenograft animals, especially in theChol-miRCtrl group. Finally, RT-PCR analysis showed thatlet-7a levels were significantly increased in Chol-let-7a-treated xenografts compared withChol-miRCtrl group (P=0.003) and blank xenograft group (P=0.001);however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively.Conclusions: Chol-let-7a, administered either continuously or intermittently, showed effective antitumor efficacy.Chol-let-7a had some off-target effects, such as mild acute hepatitis-like inflammation and non-specific drug-induced kidney injury. The intermittent dosing regimen resulted in less damage than the continuous regimen, while maintaining relatively satisfactory antitumor efficacy, which could be useful for the investigation and possible clinical use of miRNA treatment regimens in the future.