Histopathological Examination Of Liver Tissues Research Articles

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses-Induced Hepatotoxicity in Rats.

Background and Aims Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.

Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats

Quetiapine is an atypical antipsychotic drug used for treatments of patients with schizophrenia. Although hepatotoxic effects related to quetiapine treatment were reported in a few studies, potential hepatotoxicity of this drug was not identified clearly. Therefore, it was aimed to evaluate possible hepatotoxic effects of quetiapine by oral administration of this drug at 10 and 20 mg/kg doses to rats for 30 days in our study. For this purpose, plasma aspartate aminotransferase, alanine aminotransferase, total bilirubin and direct bilirubin levels as markers of hepatotoxicity were determined and histopathological examination was performed in liver tissues. According to our results, serum aspartate aminotransferase and alanine aminotransferase levels were significantly increased in quetiapine-administered groups, whereas total and direct bilirubin levels were significantly increased in high dose group. Histopathological examination of liver tissue indicated that necrotic areas were observed in 10 mg/kg quetiapine-administered group whereas necrotic areas were present and sinusoidal dilatation was observed in 20 mg/kg quetiapine-administered group. According to these results, we concluded that quetiapine may induced hepatotoxic effects in rats, dose-dependently.

Hypocholesterolemic effects of watermelon fruit rind on rats

PurposeWatermelon (Citrullus lanatus) fruit and its rind are known to contain phytochemicals that may have health benefits. The aim of this paper is to investigate the potential hypocholesterolemic effect of watermelon fruit rind (WR) using rats who are fed a high-cholesterol diet.Design/methodology/approachRats were divided into six groups and fed diets for eight weeks containing normal control diet or normal control diet with either 1% cholesterol, 5% WR, 10% WR, 1% cholesterol + 5% WR or 1% cholesterol + 10% WR. Triglycerides, total cholesterol and lipoprotein levels in serum and liver samples were determined, and histopathological examination of liver tissues was carried out.FindingsDiets containing 1% cholesterol led to hypercholesterolemia, characterized by increased levels of total cholesterol and low-density lipoproteins in rat serum and liver samples. Incorporation of 10% WR into the diet of the otherwise hypercholesterolemic rats led to significant reduction in serum levels of total cholesterol (from 266.2 to 222.7 mg/dL) and low-density lipoproteins (from 159.5 to 94.4 mg/dL). In addition, these rats also exhibited improvements in hepatic tissue structure compared to the hypercholesterolemic rats.Originality/valueThese results support the potential use of WR as a hypocholesterolemic agent. Further research is needed to ascertain the hypocholesterolemic effect of WR in human.

Therapeutic role of calcium and vitamin K3 in chemically induced hepatocarcinogenesis – new tools for cancer treatment

HCC has been reported to be immensely occurring carcinoma worldwide. Recent days the mortality occurred due to liver cancer has also been found to be increased at an alarming speed affecting mostly the young patients. The aim of the current study was to decipher the role of calcium and vitamin K3 in the treatment of chemically induced hepatocarcinogenesis in the male Wistar rats. Liver cancer was induced via a subnecrogenic dose of 160 mg/kg body weight, diethylnitrosamine (DENA) when associated with fasting/refeeding in male Wistar rats. It elevated the serum glutamate oxaloacetate (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total cholesterol (CH), triglycerides (TG), alfa-fetoprotein (AFP) and reduced high-density lipoprotein (HDL). Histopathological examination of liver tissue showed marked carcinogenicity of the chemical carcinogen. Food, water intake and animal weights were also assessed, respectively. The animals exposed to DENA showed a significant decrease in the body weight. The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of calcium and Vit K (ad libitum) combination at higher dose than the normal dietary requirement (3 mg/kg) daily for 12 weeks p.o. Physiological and biochemical analysis showed the beneficial effects of calcium and vitamin K3 combination in the animals exposed to DENA. The results deciphered the beneficial effects of calcium and vitamin K3 in combination.

Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression

AimsLysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. Main methodsHepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson’s trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. Key findingsSilymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. SignificanceSilymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF.

Impact of Mesenchymal Stem Cells and Vitamin D on Transforming Growth Factor Beta Signaling Pathway in Hepatocellular Carcinoma in Rats

Background:Transforming growth factor-beta (TGF-β) signaling is recognized as being critical for carcinogenesis. Vitamin D has proved to exert numerous tumor suppressive effects. Effects of bone marrow derived mesenchymal stem cells (BM-MSCs) on tumor progression are still controversial. The present study was conducted to evaluate the effects of BM-MSCs and vitamin D on TGF-β signaling in an experimental hepatocellular carcinoma (HCC) model in rats.Materials and Methods:The study was conducted on fifty female white albino rats divided equally into 5 groups: controls, HCC induced by diethyl-nitrosamine (DENA) and carbon tetrachloride (CCl4), HCC plus MSCs, HCC plus vitamin D and HCC plus both MSCs and vitamin D. The following parameters were assessed in rat liver tissues: TGF-β and Smad2 protein levels by ELISA and western blotting, respectively, gene expression of Smad3, Smad7, Snail, HNF4α and MMP-2 and histopathological lesions. Serum levels of alpha fetoprotein (AFP), ALT and albumin were also assessed.Results:TGF-β protein levels and gene expression of its downstream effectors (Smad3 and Snail), in addition to Smad2 protein levels were significantly higher in the HCC group than in the control group. On the other hand, they were significantly down-regulated in all treated groups with most significant amelioration with both MSCs and vitamin D. Also, the serum levels of AFP were significantly increased in the untreated HCC group, and this was again reversed in all treated groups. Histopathological examination of liver tissue revealed that administration of MSCs or vitamin D into HCC rat group improved the histopathological picture with residual tumor pathology, while administration of both MSCs and vitamin D showed better restoration of liver parenchyma. These data suggest that the TGF-β signaling pathway could be used as a therapeutic target in HCC.

Liver histopathological alteration after repeated intra-tracheal instillation of titanium dioxide in male rats.

The present study designed to evaluate the toxic effect of anatase TiO2 NPs on BALF biochemical changes and liver alteration in rats. Titanium dioxide (TiO2) nanoparticles (NPs) are utilized in food color additives and cosmetics worldwide. Humans uptake these nanoparticulate by different routes and may exhibit potential side effects, lags behind the rapid development of nanotechnology. Sixty-three mats rats were used. Included by the control group and the experimental groups treated twice a week with 0.5, 5, 50, 1.5, 15, 150 mg/kg of nano-TiO2 (size 21 nm), for four consecutive weeks. Animals were sacrificed at 4 days, a month and three months post-instillation. The levels of tumor necrosis factor - α (TNF-α) and macrophage inflammatory protein- 2 (MIP-2) were measured in the lung homogenate and in the bronchoalveolar lavage fluid (BALF) supernatants by enzyme-linked immunosorbent assay (ELISA) and histopathological examination of liver tissue was performed. The results showed that TiO2 NP induces many alterations in the liver structure after 4 days, a month and reduced after 3 months from intratracheal instillation. This included liver heavy infiltration of inflammatory cells, an increase of collagen density in portal triads, beginning of fibrosis formation and Glisson capsule thickness increase and TiO2 NPs reached the liver tissue after a month from exposure at all doses especially low doses (0.5, 1.5, 5) mg/kg of TiO2 NPs. The immune system was strongly responded in the groups treated with high doses (15, 50, 150) mg/kg of TiO2 NP leading to raising the concentration of α-TNF, and MIP-2 in BALF while they decrease in tissue homogenate.

Biochemical and Molecular Studies on Bone Marrow Derived Stromal Stem Cells on Liver Injuries in Rats

Liver is a remarkable vital organ, it is responsible for metabolizing the different food elements, filtering and detoxifying poisons in the blood to remove numerous toxic compounds. Liver affections are essentially caused by harmful chemicals (certain anti-infection, paracetamol, carbon tetrachloride, aflatoxins, per oxidized oil and so on.), overabundance utilization of liquor, immune system issue and disease. Up till now, orthotropic liver transplantation is the most powerful treatment of liver infections. Because of the deficiency of donors, high costs, the number of patients who can profit by this methodology is extremely constrained. Recently, cell based treatments have been explored as other option to entire liver transplantation. Thirty rats were separated into three equivalent groups (n=10, each). Group 1: control; Group 2: was infused peritoneally with acetaminophen (300 mg/kg); Group 3: was injected intra peritoneal with acetaminophen (300 mg/kg), then injected intra-venous with mesenchymal stromal stem cells (1 million BM-MSCs/kg). Blood samples for estimation of liver functions, and liver samples for detection of homing labeled MSCs with red fluorescent cell linker dye (PKH26), gene expression of matrix metalopeptidase (MMP2), tissue inhibitor metalopeptidase (TIMP) and histopathological examination were collected . The infusion of BM-MSCs enhanced liver capacities test, MMP2 and TIMP. Histopathological examination of liver tissue demonstrated critical antifibrotic impact, improvement in the hepatic structure as compared to the second group. It could be concluded that BM-MSC is effective in treatment of liver damage by upgrading hepatocyte recovery through enhancing the liver stress and inflammatory signaling by improving MMP2 and TIMP, besides it has a significant antifibrotic effect. The MSCs stem cell is an attractive cell source for regenerative medicine.

Genistein Ameliorates Cyclophosphamide - Induced Hepatotoxicity by Modulation of Oxidative Stress and Inflammatory Mediators.

AIM:The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats.MATERIAL AND METHODS:Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted.RESULTS:The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner.CONCLUSION:The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage.

Bile duct ligature in young rats: A revisited animal model for biliary atresia

Biliary atresia leads to cirrhosis in the vast majority of patients and constitutes the first cause of paediatric liver transplantation. Animal models allow us to understand the molecular basis and natural history of diseases. The aim of this study is to describe a surgically created animal model of biliary atresia with emphasis in long-term liver function. Forty-two 3-week-old Sprague- Dawley rats were randomly divided into two groups: bile duct ligature (BDL) and control. The animals were sacrificed on the 2nd, 4th, and 6th postoperative weeks. Blood samples were collected for liver function analysis. The spleen to body weight ratio was determined. Histopathological examination of liver tissue was performed by hematoxylin-eosin and Sirius red staining. Collagen quantification was determined by using colorimetric digital image analysis and was expressed as a percentage of total liver tissue area. Quantitative real-time polymerase chain reaction was performed to analyse gene expression levels of transforming growth factor-β1 (Tgfb1) and apeline (Apln) genes. Statistical analysis was performed where P<0.05 was considered significant. Animals from BDL group developed increasing cholestasis with clinical and laboratory features. Splenomegaly was detected at 4th and 6th week (P<0.05). Histological evaluation of the liver showed ductular reaction, portal fibrosis and bile plugs. Collagen area to total liver tissue area had a median of 2.5% in the control group and 6.5 %, 14.3 % and 37.7 % in BDL rats at 2nd, 4th and 6th weeks, respectively (P<0.001). Tgfb1 mRNA expression level was significantly higher at 6th week (P<0.001) in BDL group when compared to control. Apln mRNA expression level was significantly higher at 4th and 6th week (P<0.001) and showed a positive linear correlation (r = 0.975, P<0.05) in BDL group when compared to control. Bile duct ligature in young rats is an animal model that recreates clinical, laboratory, histological and molecular findings of biliary atresia. Bile duct ligature constitutes a good animal model to investigate therapeutic approaches for modifying the progression of liver fibrosis in biliary atresia.

Antioxidant and hepatoprotective effects of Capparis spinosa L. fractions and Quercetin on tert-butyl hydroperoxide- induced acute liver damage in mice

The present study investigates the antioxidant and hepatoprotective effects of Capparis spinosa L. and Quercetin in tert-butyl hydroperoxide (t-BHP) induced acute liver damage. Different fractions of C. spinosa were examined for total phenolic content and antioxidant property. Among these fractions, hydroalcoholic extract was used to assess the hepatoprotective effect in tert-butyl hydroperoxide (t-BHP) induced hepatotoxicity model by determining serum biochemical markers, sleeping time and antioxidant assay such as reduced glutathione (GSH) as well as histopathological examination of liver tissues. The total phenolic and Quercetin contents of hydroalcoholic fraction were significantly higher than other fractions. It also showed high antioxidant activity. Pretreatment with hydroalcoholic fraction at the dose of 400 mg/kg and Quercetin at the dose of 20 mg/kg showed liver protection against t-BHP induced hepatic injury, as it was evident by a significant decrease in serum enzymes marker, sleeping time and MDA and an increase in the GSH, SOD and CAT activities confirmed by pathology tests. The final results ascertained the hepatoprotective and antioxidant effects of C. spinosa and Quercetin in a dose-dependent manner. Moreover, this study suggests that possible mechanism of this protection may be associated with its property of scavenging free radicals which may be due to the presence of phenolic compounds.

Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver fibrosis

Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group (n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests. Results: ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group (P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003). Conclusion: ALHXW treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis.

Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma–induced liver fibrosis

Liver fibrosis is a pathological process complicating schistosomiasis. It is an active process of continuous extracellular matrix accumulation. In Egypt, schistosomiasis re-infection is a continuing problem especially in rural areas. In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor as a new molecular target for Schistosoma–induced liver fibrosis, in addition to exploring its effect as antischistosomal drug. The effect of GDC-0449 alone or combined with Praziquantel was tried experimentally in infected mice with Schistosoma mansoni. Fifty CD-1 Swiss female albino mice were used, forty mice were infected with Schistosoma mansoni cercariae. Animals were grouped into five groups; uninfected control, infected untreated, infected treated with Praziquantel (500mg/kg/day) for two days, infected treated with GDC-0449 (40mg/kg/day) for seven days, and infected treated with combined Praziquantel and GDC-0449. Parasitological and chemical parameters, hydroxyproline level and liver granuloma were assessed. Liver fibrosis was reduced significantly evidenced by reduced hydroxyproline levels [P<0.01 for combined (Praziquantel/GDC-0449) treatment groups, P<0.001 for GDC-0449-treated group]. Also, histopathological examination of liver tissues revealed that the mean diameter of granulomas was statistically reduced (P=0.001) with a reduction rate of 24.4% on treatment with GDC-0449. In GDC-0449/Praziquantel combined treatment group, number and mean diameter of the granulomas were reduced significantly P<0.001, and P=0.001 respectively. No antischistosomal effect was recorded for GDC-0449 in this study.

Curcumin Attenuates N-Nitrosodiethylamine-Induced Liver Injury in Mice by Utilizing the Method of Metabonomics.

N-Nitrosodiethylamine (DEN) exists as a food additive in cheddar cheese, processed meats, beer, water, and so forth. It is a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination of liver tissues and biomarker detection in serum and livers, it was demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level, and COX-2/PGE2 pathway. Furthermore, curcumin attenuated metabolic disorders via increasing concentration of glucose and fructose, and decreasing levels of glycine and proline, and mRNA expression of GLUT1, PKM and FASN. Docking study indicated that curcumin presented strong affinity with key metabolism enzymes such as GLUT1, PKM, FASN and LDHA. There were a number of amino acid residues involved in curcumin-targeting enzymes of hydrogen bonds and hydrophobic interactions. All in all, curcumin exhibited a potent liver protective agent inhibiting chemically induced liver injury through suppressing liver cellular metabolism in the prospective application.

Chronic Hepatitis B Reactivation Subsequent to Chronic Hepatitis C Treatment: A Case Report

Patients, who are coinfected with hepatitis B and C, are at high risk for a progression to severe liver disease (cirrhosis, decompensated liver disease), hepatocellular carcinoma, and unresponsiveness to treatment. In this article, a case who developed a reactivation of chronic hepatitis B subsequent to Chronic Hepatitis C (CHC) treatment is presented. A 42-year-old woman with HBV and HCV was admitted to infectious diseases clinic with a major complaint of fatigue for three months. Laboratory tests revealed an elevated alanine transaminase of 182 IU/L (Normal range: 0-55 IU/L), elevated aspartate transaminase of 150 IU/L, serum HCV-RNA levels of 2080195 IU/mL (genotype 1b), and HBV-DNA of 1184 IU/mL. The results of other laboratory tests were within the normal range and remained to be normal during the follow-up. Pegylated interferon alpha-2a (180 mcg/week) and ribavirin (1200 mg/day) were administered for the treatment of CHC for 48 weeks. After one year of CHC treatment, our case was admitted with the elevation in liver enzymes and HBV-DNA of 878215 IU/mL. The histopathological examination of liver tissue revealed a mildly active histologic activity (6/18) and a mildly active histological activity (1/6) according to ISHAK scoring. Tenofovir disoproxil tablet (245 mg/day) was initiated for the chronic hepatitis B treatment. The patient is followed up at the ambulatory clinic of infectious diseases. As a result, patients coinfected with HBV and HCV should be followed up for the reactivation of HBV after CHC treatment with either pegylated interferon-based therapy or oral direct-acting antiviral agents in the medium-term, and the cirrhosis and hepatocellular carcinoma in the long-term.

Effect of fast neutrons-irradiated diets on liver structure and function of male albino rats

Presently, there is a growing need for the technology of food irradiation since it provides an effective process in food preservation and quality improvement . Accordingly, this study was designed to investigate the effects of fast neutron- irradiated wheat grains on the structure and function of the liver of albino rats. . Rats were categorized into two main groups (G1 & G2 ) ,40 animals for each. Each group was subdivided equally to four subgroups ( A,B,C&D for G1 and AA,BB,CC&DD for G2). A and AA served as control animals for G1 and G2 respectively and given non-irradiated diets ,while B,C&D were given irradiated diets at three different fluencies of fast neutrons;4.3×105 ,2.0×106 and 1.4×107 n/Cm2 respectively .But ,BB,CC and DD were given a diet of irradiated wheat of the second generation ( harvested from cultivation of the irradiated grains of the first generation ) at the same previous fluencies. Serum albumin and total protein, biochemical markers of liver function ( ALP, ALT and AST ) and the histopathological alterations of liver would be tested. Rresults of the present work highlight the detectable effect of irradiated wheat grains by the moderate ( 106 ) and the highest ( 107 ) fluencies of fast neutrons on albumin and total protein concentrations ( as indices of liver synthetic capacity). However the lowest (105) fluency exerted no detectable effect. The application of feeding with grains of the 2nd. generation on G2 experimental subgroups ( BB, CC & DD ) recorded a slight increase did not approaching a significant value ( p > 0.05 ) concerning albumin and total protein levels, in all treated animals Concerning the enzyme activities of alkaline phosphatase ( ALP ) and transaminases ( ALT & AST ) , they recorded minor fluctuations between the positive and negative range in the exposed animals of both groups ( G1 & G2) as compared to controls . But , these little differences did not approaching a significant record except for ALP inBB subgroup of G2 . On histopathological examination of liver tissue , sporadic spontaneous lesions , known to occur in rats , were the only findings , with no specific relation to the studied stress factor .Therefore , it can be concluded that fast neutron-irradiated diets does not cause changes of any toxicological significance in experimental animals , at the conditions of the current experiment , in spite of minor changes in biochemical parameters . But , it is necessary to demonstrate the safety of radiationprocessed food in case of human consumption.

Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl4) via anti-inflammatory and antioxidant mechanism

SummaryObjectives: Dasatinib, a potent and broad-spectrum tyrosine kinase inhibitor, is approved for the treatment of imatinib-resistant chronic myelogenous leukemia. The aim of this study was to evaluate the anti-fibrotic, anti-inflammatory and antioxidant effects of this agent against CCl4-induced hepatic fibrosis and oxidative status.Materials and methods: Experimental fibrosis was induced in Wistar male rats by 12 weeks of CCl4 administration (i.p.). During the last 8 weeks of injection, rats were gavaged daily with Dasatinib (10 mg/kg). To evaluate anti-inflammatory and anti-fibrotic effects of Dasatinib, histopathological examination of liver tissue was performed and serum ALT and AST activities, oxidant, antioxidant parameters and hepatic tumor necrosis factor alpha (TNF-α) were examined. Moreover, transforming growth factor (TGF-β1), platelet derived growth factor (PDGF) and TNF-α mRNA expressions were also evaluated by real time polymerase chain reaction.Results: Dasatinib administration induced a significant reduction of ALT and AST activities (p < .001) and Malondialdehyde (MDA) content in CCl4 injected rats (p < .05). Concomitantly hepatic protein and mRNA expression of TNF-α, mRNA expression of TGF-β1 and PDGF were increased due to CCl4 intoxication (p < .001), but Dasatinib treatment could significantly ameliorate these mediators at the level of gene expression (p < .01) and protein level of TNF-α (p < .001). The necro-inflammatory changes in histopathological finding, nitric oxide and hydroxyproline level were also increased during 12 weeks of CCl4 administration which was significantly attenuated by Dasatinib (p < .01).Discussion and conclusion: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.

Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity.

Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity. Subsequently, mice were overdosed with acetaminophen followed by treatment with the pannexin1 channel inhibitor 10Panx1. Sampling was performed 1, 3, 6, 24 and 48h after acetaminophen administration. Evaluation of the effects of pannexin1 channel inhibition was based on a number of clinically relevant readouts, including protein adduct formation, measurement of aminotransferase activity and histopathological examination of liver tissue as well as on a series of markers of inflammation, oxidative stress and regeneration. Although no significant differences were found in histopathological analysis, pannexin1 channel inhibition reduced serum levels of alanine and aspartate aminotransferase. This was paralleled by a reduced amount of neutrophils recruited to the liver. Furthermore, alterations in the oxidized status were noticed with upregulation of glutathione levels upon suppression of pannexin1 channel opening. Concomitant promotion of regenerative activity was detected as judged on increased proliferating cell nuclear antigen protein quantities in 10Panx1-treated mice. Pannexin1 channels are important actors in liver injury triggered by acetaminophen. Inhibition of pannexin1 channel opening could represent a novel approach for the treatment of drug-induced hepatotoxicity.

Hepatoprotective effect of Zataria Multiflora Boiss against malathion-induced oxidative stress in male rats

This study was aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. multiflora) against oxidative stress induced by malathion (MT) in male Wistar rats in comparison to N-acetylcysteine (NAC). Rats were randomly divided into 6 groups (n: 8) and treated daily for 28 days. They received MT (150 mg/kg), Z. multiflora methanolic extract (50, 100, and 200 mg/kg), and NAC (200 mg/kg) alone or in combination. This study included a histopathological examination of liver tissue in parallel with measurement of serum aminotransferases. Activities of antioxidant enzymes, total glutathione (GSH), and lipid peroxidation end products in plasma and tissue were also measured. Subacute exposure of rats to MT resulted in a significant morphological change in tissue, an increase in plasma aminotransferases, and oxidative damage. Both NAC and Z. multiflora at the dose of 200 mg/kg significantly reduced MT-induced oxidative stress by inhibiting lipid peroxidation, increasing the content of glutathion, and restoring the activities of superoxide dismutase and catalase. Biochemical and histological observations also showed a dose dependent hepatoprotective effect of Z. multiflora extract against subacute exposure to MT.

Hepatoprotective Effect and Chemical Assessment of a Selected Egyptian Chickpea Cultivar.

Chickpea (Cicer arietinum) is a legume of the family Fabaceae, subfamily Faboideae. In Egypt, chickpea seeds are usually consumed at raw green and tender stage, or in the form of mature dry seeds. In our previous study, ‘Giza 1’ seeds exhibited stronger antioxidant activity and higher total phenol content than those from other Egyptian cultivars. In order to assess the biological potential of ‘Giza 1’ seeds in vivo, the extraction procedure was reproduced here. The extract was standardized using liquid chromatography coupled to diode array detector and tandem mass spectrometry (MS/MS) to evaluate their hepatoprotective effect on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and acute toxicity. Administration of the extract to rats in doses up to 2 g/Kg) did not cause any mortalities or observable signs of toxicity. Further, the plant extract showed a strong hepatoprotective activity based on assessing serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and levels of albumen, globulin, total protein, total cholesterol, high density lipoprotein, triglycerides, and low density lipoprotein. The antioxidative activity was evaluated by assessing hepatic catalase and superoxide dismutase activity as well as reduced glutathione, and malondialdehyde levels. Additionally, anti-inflammatory activity was observed as the extract significantly lowered the hepatic tumor necrosis factor α content. Histopathological examination of liver tissues indicated that the extract-treated animals showed almost normal hepatic architecture with fewer pathological changes. In conclusion, the current results suggest that the chickpea extract possesses an excellent safety profile with very low acute toxicity. Also, it exhibits a significant hepatoprotective effect against CCl4-induced liver injury in rats. This can be attributed, at least partly, to the antioxidant and anti-inflammatory activity of the isoflavones and phenolic acids content of the extract.