Histopathological Examination Of Liver Tissues Research Articles

Panax Ginseng alleviates thioacetamide-induced liver injury in ovariectomized rats: Crosstalk between inflammation and oxidative stress.

Liver diseases impose a substantial health problem. Female hormones play a crucial role in the protection against chronic inflammatory diseases. Fifty female rats were allocated into five groups (n = 10). Group I comprised sham-operated rats. The remaining groups underwent ovariectomy at the beginning of the experiment. Group II served as the ovariectomy-control group. Groups III, IV & V received thioacetamide (TAA; 300 mg/kg; i.p.) to induce liver injury 6 weeks after ovariectomy. Group III served as the TAA-control group. Groups IV & V received panax ginseng (100 and 300 mg/kg/day, p.o.) for 6 weeks post TAA administration. All groups were investigated for liver function tests along with total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α) and advanced glycation end products (AGEs). Histopathological examination of liver tissues was performed followed by immunohistochemical staining for nuclear factor kappa-B (NF-kβ p65) and myeloperoxidase (MPO). Ovariectomized-rats showed a non-significant change in the measured parameters while TAA administration resulted in significant liver damage. Panax ginseng at both dose levels significantly improved the serum liver function tests and TAC along with decreasing the AGEs and TNF-α. It also restored the histopathological picture of liver tissue and decreased hepatic tissue inflammation via reduction of MPO and NF-kβ p65 immunoreactivity. The current study is the first to elucidate the effect of panax ginseng against TAA-induced liver injury in ovariectomized rats which mimic aged post-menopausal estrogen-deficient females. The study demonstrates the crosstalk between AGEs, NF-kβ and MPO in the modulation of inflammation. Panax ginseng possesses antioxidant and anti-inflammatory properties.

Naringenin alleviates hepatic injury in zinc oxide nanoparticles exposed rats: impact on oxido-inflammatory stress and apoptotic cell death

Human exposure to nanoparticles became unavoidable secondary to their massive involvement in a multitude of industrial applications. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles in biological applications. Naringenin (NAR), a citrus-derived flavonoid, has favorable biological properties that promote human health. The present study was carried out to investigate the possible defensive role of NAR versus ZnONPs provoked hepatic injury in rats through an evaluation of liver enzymes, hepatic biomarkers of oxidative stress, inflammatory process, apoptotic cell death along with histopathological examination of liver tissue. Therefore, 32 adult rats were randomly divided into four equal groups as control, NAR, ZnONPs and co-treated ZnONPs with NAR groups. All treatments were administered for 14 days. Our results showed that ZnONPs induced hepatic injury as documented by the marked increased in hepatic enzymes activities, disturbed hepatic oxidant/antioxidant balance, increased hepatic inflammatory reactions, in addition to, extensive hepatic morphological alterations, marked collagen fibers accumulation as well as overexpression of apoptotic BAX and the noticeable intensified positive nuclear staining for nuclear factor Kabba-b in hepatic tissues. Concurrent NAR supplement to ZnONPs- treated rats significantly declined liver enzymes activities, restored oxidant/antioxidant balance, reversed inflammation, induced fewer collagen fibers accumulation, and antagonized BAX-mediated apoptotic cell death in hepatic tissues. We concluded that concurrent NAR supplement to ZnONPs treated rats improved hepatic function and structure by its antioxidant, anti-inflammatory and antiapoptotic potentials.

The role of different edible vegetable oils as hypolipidemic agents on experimental hyper-lipidemic rat model

Hyperlipidemia is a common disorder that includes genetic and functional disorders represented by elevated lipid levels in the body. The objective of this study was to characterize the physicochemical parameters of the edible seed oils separated from linseed, soybean, olive seed and blends from different proportion, then identify the optimum blend in controlling serum lipid profile in experimental hyperlipidemic rat model. Histopathological examinations of the liver section were carried out to support the laboratory investigation. Sixty male albino rats were used for the study. The animals were divided into ten groups, where group 1 represents negative control, while rats in group 2 received high fat diet and served as positive control. Groups from 3 to 10 were fed high-fat diet and then supplemented with different vegetable oils. At the termination of the 6 weeks trial, blood samples and organs were collected for estimation of lipid profile. Results showed that rats administered different vegetable oils significantly decrease levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) cholesterol as well as increase levels of high-density lipoprotein (HDL) cholesterol in comparison with rats fed high-fat diet. Histopathological examination of liver tissue in positive control showed severe dilatation and congestion in the central vein with fatty change in the surrounding adjacent hepatocytes. While administration of different vegetable oils showed marked improvement in the histological feature of liver tissues. In conclusion, the findings suggest that balanced blend from linseed, soybean and olive oils help in controlling hyperlipidemia and restoring the lipid profile.

Evaluation of the hepatotoxic potential of citalopram in rats

Background and Aims: Citalopram is a selective serotonin reuptake inhibitor with a high potency which is occasionally prescribed and used to treat major depression associated with mood disorders as a first-line drug. According to the results of previous studies, evidence of hepatotoxicity related to citalopram treatment were limited and conflicting. Therefore, we aimed to evaluate the hepatotoxicity potential of sub-chronic citalopram administration. Methods: Citalopram was administered to female rats orally in 5 and 10 mg/kg for 30 days. After the exposure period, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin levels as biomarkers of hepatotoxicity were measured and histopathological examination of liver tissues was performed. Additionally, GSH levels of liver tissues were determined. Results: The risk of hepatotoxicity related to citalopram was shown by significant increases of serum hepatic biomarkers, AST, ALT, and total bilirubin in citalopram-administered groups. According to the histopathological findings, hepatocellular necrosis, hepatic nuclear asymmetry, and disarrangement of hepatic cord cells (hepatocytes) were prominent in the 10 mg/kg citalopram-administered group. On the other hand, there was no significant difference among the groups in terms of GSH levels. Conclusion: The results suggested that the administration of citalopram might cause hepatotoxic effects, depending on the dose.

Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

PurposeLiver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. MethodsAdult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. ResultsDiacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. ConclusionThese results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Preventive Role of Soy Protein in Fructose Induced Metabolic Dysfunction in Rats via Inhibition of Nuclear Factor kappa B Pathway

Soy protein is an important component of soybeans that has beneficial role in improving insulin resistance. Nuclear factor kappa B (NF-κB) is a crucial pathway that has been implicated in the development of metabolic syndrome. Our study aimed to examine the protective effect of soy protein isolate - as a natural NF-κB inhibitor - and its possible mechanism of action in amelioration of inflammatory and metabolic disorders induced in male albino rats by high fructose diet (10% w/v) via using synthetic NF-κB inhibitor (IMD-0354). Rats were randomized into normal control group, soy group, NF-κB inhibitor (IMD-0354) group, high fructose group, high fructose with soy group, high fructose with NF-κB inhibitor group, high fructose with soy and NF-κB inhibitor group. Serum glucose, serum insulin, serum free fatty acids, insulin resistance (HOMA-IR), NF-κB, phosphorylated insulin receptor (pISR), carbohydrate-responsive element-binding protein (ChREBP) were determined and histopathological examination of liver tissue was performed. The concurrent administration of IMD-0354 and/or soy protein with high fructose significantly increased pISR and decreased FFAs, NF-κB, glucose, insulin, HOMA-IR, and ChREBP as well as improved the pathological conditions of the livers. The metabolic and inflammatory disorders induced by chronic consumption of fructose could be inhibited by co-administration of soy protein through regulation of NF-κB signalling pathway.

Epigenetic Programming Through Breast Milk and Its Impact on Milk-Siblings Mating

BackgroundThe epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations.ResultsA cross-fostering model using a/a and Avy/a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues.ConclusionOur findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.

Toxic effect of some heavy metals on hematology and histopathology of major carp (Catla catla).

The current study was conducted to assess the hematological and histopathological changes in major carp (Catla catla) exposed to different concentrations of copper (Cu) and cadmium (Cd). For this purpose, Catla catla fish, weighing approximately 230-235 g, were randomly divided into four groups and then exposed to acute doses of Cu (1.25 ppm), Cd (4.5 ppm), and their mixture (2.25 ppm) for 96 h and then 20, 30, and 40% respectively for a period of 30 days. Results showed that red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), lymphocyte, and monocyte decreased significantly, while the total white blood cell count and neutrophil population significantly increased in experimental groups as compared with the control one. Histopathological examination of liver tissues showed karyorrhexis, hepatic cells degeneration, congestion, and hemorrhages. Microscopic analysis of gills' sections revealed lamellar atrophy, telangiectasia, and necrosis of lamellar epithelial cells. In the kidneys, different histopathological ailments like atrophy of glomeruli, necrosis of renal tubular cells, increased urinary spaces, degeneration of renal tubules, and melanomacrophage aggregates were observed, while in the intestine, atrophy of villi, sloughing of epithelial villi, and congestion were seen after 30 days of exposure. In conclusion, the study indicates that exposure to Cu and Cd for longer period of time causes adverse hematological and histopathological changes in Catla catla fish.

Effect of different feeding regimes on the growth performance, antioxidant activity, and health of Nile tilapia, Oreochromis niloticus

The present study aimed to evaluate the effects of using different feeding regimes on the growth performance, economic efficiency, antioxidant status, and blood biochemical parameters of Nile tilapia, Oreochromis niloticus fingerlings for 10 weeks. Three hundred and sixty healthy fingerlings with average initial weight 16.9 ± 0.44 g were randomly allotted to 2 × 3 factorial design consisted of two feeding frequencies (once or twice a day) and three feeding intervals for each; regular feeding (daily feeding) or intermittent feeding; every other day (one day of feed one day of fasting) and every third day (one day feed two days fasting), respectively. The interaction occurred between feeding frequencies and intervals resulted in non-significant differences (P > .05) in the final body weight (BW) and body weight gain (BWG) between all experimental groups except for the group of fish fed once every third day that was lower than the group of fish fed twice daily (P < .05). However, the feed conversion ratio (FCR), protein efficiency ratio (PER), and protein productive value (PPV) were not influenced by the changes in the feeding frequency or interval. The daily feed intake was increased in intermittent feeding over daily feeding (P < .05). The expected weight gain for each daily feed intake was increased in fish fed twice every third day (P < .05). The dry matter content was increased (P < .01) in the fish fed twice daily. The crude protein content was decreased (P < .05) in the body of fish fed once every third day. The body fat content was decreased (P < .05) in fish fed twice every other day and fish fed every third day either once or twice. The body ash was increased (P < .05) in fish fed once every other day and twice every third day. The serum albumin was higher (P < .05) in fish fed once over those fed twice. The serum triglycerides level was increased (P < .05) in fish fed every third day compared to those regularly-fed. The serum level of glucose was higher (P < .05) in fish fed once every other day and twice every third day. Fish fed every third day had higher (P < .05) SOD activity than those regularly-fed. Mild to moderate alterations were observed in the histopathological examination of liver tissues from fish fed intermittently. The intestinal structure of fish regularly or intermittently-fed were within the normal range. Economically, intermittent feeding decreased the feed costs over regular feeding but the feed cost/kg gain was not affected (P < .05). It can be concluded that fish fasted and re-fed once or twice every other day and those that fasted and re-fed twice every third day can compensate for growth, while fish fasted and re-fed once every third day showed poor performance than regularly fed fish. Fasting can improve the antioxidant status of fish. However, intermittent feeding induced some degenerative changes in the histological structure of the liver.

Effects of Aloe woodii gel methanolic extract on the liver function changes induced by high sugar intake in female albino rats

Consuming sugar-added foods and sweetened beverages is being a familiar habit associated with many diseases. Folk information in Yemen indicates the therapeutic effects of Aloe woodii on some diseases. So, the aim of this study is to evaluate the ameliorated effect of Aloe woodii gel extract on liver lesions in female rats induced by high table sugar intake. This study lasted 11 weeks and was divided into two periods. The first period was for high table sugar supplement, whereas the second was for the treatment by the methanolic extract of Aloe woodii gel. At the end of the experiment, body weights were recorded, blood samples were taken, and liver samples were also taken for the histopathological examination supported by quantitative measurement. Results: There was no remarked change in the body weights between groups, but there was an accumulation of the visceral fat and an elevated of alanine aminotransferase (ALT) level in the sugar group. Histopathological examination of liver tissues in the sugar group revealed many degenerated manners such as vacuolation and/or ballooning of hepatocytes and inflammation. However, the treatment by Aloe woodii gel led to an ameliorate of the histopathological changes, but had no effect on ALT level. Conclusion: High sugar supplement induced high visceral fat accumulation and many lesions in liver tissue, whereas Aloe woodii treatment ameliorated these effects.

Investigating the ameliorative effects of the aqueous extract of Pleurotus ostreatus on cyclophosphamide-induced cytotoxicity in rabbits

This study investigated the ameliorative effect of aqueous extract of Pleurotus ostreatus (APO) against cyclophosphamide-induced cytotoxicity in rabbits. Seventy-two healthy rabbits were divided into eight groups each with nine rabbits. Rabbits in groups 1, 2, 3 and 4 (CPA-treated groups) were each given a single oral dose of 50 mg/kg of cyclophosphamide (CPA), however rabbits in groups 2, 3 and 4 were post-treated with 5.0, 7.5 or 10 mg/kg APO on day 1 and throughout the experiment. Rabbits in groups 5, 6, 7 and 8 (CPA-untreated groups) were given only 0.0, 5.0, 7.5 and 10 mg/kg APO per day, respectively throughout the experiment. The experiment lasted 15 days. Serum chemistry analyses and histopathological examination of liver tissues were carried out. Serum creatinine, bilirubin, globulin and total protein concentrations observed in CPA-treated groups were higher (P < 0.05) than those of CPA-untreated groups. Highest (P < 0.05) values for total protein (83.60 g/dl) and globulin (43.16 g/dl) were recorded in CPA-treated groups administered 10.0 mg/kg APO per day. Haematological measurements (packed cell volume, haemoglobin, white blood cell, platelet and red blood cells) in CPA-treated groups were lower (P < 0.01) in comparison to those of CPA-untreated groups. However, an increase (P < 0.01) in the values of these parameters was observed following post-treatment of rabbits in the CPA-treated groups with 7.5 and 10.0 mg/kg APO per day. The findings of this study thus indicate that aqueous extract of Pleurotus ostreatus has the potential to ameliorate CPA-induced renal injury and myelosuppression in a dose-dependent manner.

Study of reactive oxygen species and adiponectin for chronic HBV infection combined with nonalcoholic fatty liver diseases

Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver (P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.

The effects and mechanism of Aronia melanocarpa Elliot anthocyanins on hepatic fibrosis

Abstract Hepatic fibrosis is a pathological change that is a major problem in chronic liver disease. As an important biologically active substance, the Aronia melanocarpa Elliot anthocyanins (AMA) has a strong anti-oxidation property and may have certain preventive and therapeutic effects on hepatic fibrosis diseases. The current research was designed for evaluation the antifibrotic effects and mechanism of AMA on CCl4-induced liver injury in mice. Mice injected with CCl4 twice a week at the same time as treated with 20 or 40 mg/kg AMA by gavage every day. After 8 weeks, biochemical parameters were used to estimate liver damage, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB), total protein (TP) and albumin (ALB). In addition, oxidative stress parameters such as superoxide dismutase (SOD) and reduced glutathione (GSH) were also studied. And the role of TNF-α, IL-1, IL-6, COX-2 as markers of inflammation at the transcriptional level. Histopathological examination of liver tissue was performed and compared to controls. Collagen I, alpha smooth muscle actin (α-SMA), transforming growth factorβ1 (TGF-β1) and SMAD2 were also evaluated as markers of fibrosis. The results showed that AMA improved CCl4-induced fibrosis, such as histopathological scores, markers of liver damage and oxidative stress. In addition, we investigated the potential mechanisms of underlying these effects, including: (1) inhibiting fibrosis by reducing the expression of inflammatory factors such as TNF-α and IL-1; (2) Prevent liver fibrosis by inactivating α-SMA expression; (3) inhibition of TGF-β1 secretion and Collagen I deposition to down-regulate the fiber reaction of HSC. In conclusion, this study illustrated the anti-fibrotic effects of AMA and may be a new candidate for the treatment of hepatic fibrosis.

Protective Activity of &amp;lt;i&amp;gt;Markhamia tomentosa&amp;lt;/i&amp;gt; (Benth.) K. Schum. (Bignoniaceae) Methanol Leaves Extract against D-Galactosamine/Lipopolysaccharide-Induced Acute Liver Injury in Mice

Markhamia tomentosa (Benth.) K. Schum. (Mt) is a Cameroonian medicinal plant, traditionally used to treat painful and inflammatory illness. This study aimed to examine the effects of methanol leaves extract (MLE) of Mt in D-galactosamine (D-GaIN)/lipopolysaccharide (LPS)-induced liver injury. The MLE (100 and 200 mg/kg), Ascorbic acid (10 mg/kg) and distilled water were administered 12 h and 1 h before intraperitoneal injection of D-GaIN (10 mg/mouse)/LPS (0.1 μg/g). Animals were sacrificed 6 h after D-GalN/LPS challenge. Liver injury was assessed biochemically by determination of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase activities. Malondialdehyde (MDA), reduced glutathione (GSH), nitrites, total protein and bilirubin levels were explored. Histopathological examination of liver tissue was also performed. Liver enzymes (ALAT, ASAT, ALP) activity, nitrites, MDA and bilirubin levels were increased, while protein level, SOD and catalase activities were significantly reduced by D-GalN/LPS administration. MLE (100 or 200 mg/kg) protected mice against D-GalN/LPS-induced death. In addition, the plant extract significantly reduced ALAT and ALP activity, exhibiting 23.00% and 62.20% protection, respectively. SOD activity and total protein were significantly (p D-GaIN/LPS-induced liver injury. The obtained results showed that MLE of Mt may possess hepatoprotective effects. Protection afforded by MLE against D-GalN/LPS-induced fulminant liver injury may result from reduction of oxidative stress.

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats.

The aim of this work was to develop ezetimibe self-micellizing solid dispersions using Kolliphor® RH40 (MS-K) as a surfactant incorporating ezetimibe (EZ) into the croscarmellose hydrophilic carrier. Different ezetimibe:Kolliphor® ratios were studied to select micellar systems that improve the dissolution properties of ezetimibe. The different formulations were characterized by means of solid state analysis by SEM, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and dissolution studies. These physicochemical studies showed a decrease from the crystalline structure of ezetimibe (EZ) to its amorphous state in the micellar systems (MS-K). A rapid dissolution profile was observed in these micellar systems compared to the drug raw material and physical mixture. Efficacy studies were conducted using a high-fat diet that induced hyperlipidemic rats. The micellar system selected (MS-K 1:0.75) revealed a significant improvement in serum levels of total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) compared to ezetimibe raw material. The histopathological examination of liver tissue also showed that this micellar system exhibited more beneficial effects on liver steatosis compared to ezetimibe raw material (EZ-RM) and the high-fat diet group (HFD). This study suggests that EZ micellar systems using Kolliphor® RH40 could enhance the antihyperlipidemic effect of ezetimibe and reduce liver steatosis.

Biochemical Study On the Effect of Morin and Rutin in amelioration of Titanium dioxide Nanoparticle Toxicity in rat liver

Background: Titanium dioxide nanoparticles (TiO2 NPs) were healthy well-known as a photocatalyst and it was extensively utilized for photocatalysed corrosion, sensor essentials, water distillation and had numerous other submission. Also, in food industry. However they also had poisonous result on animals uncovered to them. Objectives: we examined the probable ameliorative result for the two flavonoids morin and rutin which had apotent antioxidant activity, against TiO2 nanoparticles-induced toxicities in rat liver. Materials and methods: Albino rats (n =70, weight 150-200g) were divided into seven groups. Group (G1) (control), G2 (treated with morin 30 mg/kg), G3 (treated with rutin 80 mg/kg), G4 (toxic group that administrated orally with titanium dioxide nanoparticles 100 mg/kg), G5 (TiO2 NPs+ morin), G6 (TiO2 NPs+ rutin), G7 (TiO2 NPs+ morin+ rutin). The evaluated parameters included liver function markers, some minerals and electrolytes, antioxidant (superoxide dismutase SOD, catalase CAT and glutathione GSH) and oxidative stress malondialdehyde (MDA) biomarkers in addition to DNA fragmentation and histopathological examination of liver tissues. Results: These experimental study showed that a significant increase of serum ALT, AST, ALP activities. Also, serum potassium (K) and phosphorous (P) levels, hepatic MDA content, comet, tail length, DNA in tail and tail moment of DNA fragmentation were detected in TiO2 NPs (G4) group indicating liver damage which compared with control group (G1) but this parameters decreased significantly in morin (G5) or rutin (G6) when compared with toxic group (G4), in combination group (TiO2 NPs+ morin+ rutin) (G7) succeeded to decrease significantly in this parameters and returns to (G1). Also, our results showed that a significant decrease in total protein, albumin, sodium (Na), calcium (Ca) levels, glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities in toxic groups (G4) but succeeded to increase significantly in this parameters in G5, G6 and G7 in compared with control group and restore it. Conclusion: TiO2NPs oral administration induced toxic effects and DNA damage in the liver that may be attributable to oxidative stress.Also, administration of morin and/or rutin with TiO2NPs offers protection against their damaging effect.

Bone marrow derived mesenchymal stem cells suppress diethylnitrosamine induced liver cirrhosis in rats

Aim: The present study was designed to explore the ability of bone marrow derived mesenchymal stem cells (BM-MSCs) to repair diethylnitrosamine (DEN)-induced liver cirrhosis (DILC) in rats. Materials and methods: Sixty male rats were divided into four groups (15 rats per group), the rats of the first group received saline, and the rats of the other three groups received DEN in drinking water. After thirty days, the rats of the third and fourth groups received 1.5x106 and 2x106 MSC infusions ,respectively. Liver function tests were estimated in serum of rats in all groups. The expression of albumin (Alb) and cytokeratin-18 (CK-18) genes were detected by reverse transcription-polymerase chain reaction (RT-PCR). Histopathological examination of liver tissue was performed. Results: Administration of BM-MSC of both doses (1.5x106 and 2x106 cells) into rats with DILC resulted in ameliorating liver functions and histopathological features compared to that received DEN only. RT-PCR analysis revealed that the expression of albumin gene increased, while CK-18 decreased in liver tissue of rats with DILC which received 2x106 BM-MSCs compared to DEN control group. Conclusion: BM-MSCs suppressed DEN-induced liver cirrhosis in rats as indicated by up regulation of albumin and CK-18 genes, as well as improvement of liver functions and architecture.

Effect of Pomegranate Seed Oil against Hepatotoxicity- Induced by Sodium Fluoride in Adult Female Rats (Part II).

This experiment was designed to evaluate the hepatoprotective effects of pomegranate seed oil against toxicity- induced by sodium fluoride and in normal rats. Twenty adult female Wistar rats were divided into four equal group and treated daily for 40 days as follows: Group C administered tap water and served as control , group T1 : received sodium fluoride 120ppm in drinking tap water, group T2: received both sodium fluoride 120ppm in drinking water and administered orally pometone (pomegranate seed oil) 30mg/kg B.W. and group T3 : administered pomegranate seed oil as in group T2 orally. Fasting blood samples were collected at 0, 20 and 40 days to estimation of some biochemical parameters and oxidative stress biomarkers . In addition, sections from liver were taken at the end of the experiment for histopathological study. The results revealed that SF (group T1) caused a significant increase in serum aminotransferases (serum alanine aminotransferase and aspartate aminotransferase) activities, total cholesterol ,total bilirubin and peroxynitrite radical concentrations, while GSH concentration was a significantly decrease. PSO caused an alleviation to the hepatic dysfunction induced by sodium fluoride (group T2) manifested through significant elevation of GSH concentration, in addition, a significant reduction in serum transaminases activity, total cholesterol, peroxynitrite radical and total bilirubin concentrations. In contrast, administration of pomegranate seed oil (group T3) showed no alterations in most of these parameters. Furthermore histopathological examination of liver tissues of group T1 manifested aggregation of mononucleated cells, proliferation of hepatocyte, cytoplasmic fat droplet and granulomatous lesion consists of aggregation of macrophage and lymphocyte. All these alteration in liver histology were modified by treatment of rats with pomegranate seed oil (group T2) and no pathological lesion was reported in group T3. On conclusion, this study documented the beneficial effect of pomegranate seed oil against the deleterious effects of SF on liver functions of adult female rats.

Propolis Extract Attenuates Sepsis-Induced Hepatotoxicity and Neurotoxicity in Male Rats

Inflammation is an important biological event in host defenses against bacterial or viral infections. However, excessive inflammatory responses by aberrantly activated macrophages, producing excess amounts of inflammatory mediators, which disrupt immune homeostasis and result in immunopathological conditions such as sepsis. Sepsis was recognized as a systemic inflammatory response syndrome after serious infections, most commonly with bacteria, which have a high mortality rate. Propolis (Prop) could be used as adjuvant therapy in the management of sepsis. The present study aimed to investigate the protective effect of Prop against sepsis-induced in rats. Evaluation of complete blood count, activity of liver function enzymes in serum; alanine and aspartate aminotransferases were recorded. Oxidant/antioxidant markers in liver tissue namely; malonaldehyde, nitrites/nitrates, glutathione disulfide, glutathione levels, catalase and superoxide dismutase activities. Also, tumor necrosis factor-alpha and prostaglandin E-2 levels in both serum and liver tissue were estimated. Furthermore, interleukin-8, cyclooxygenase-2 and inducible nitric oxide synthase genes expression were determined. Histopathological examination of liver tissue was investigated. Brain neurotransmitters; Dopamine, Norepinephrine and 5-hydroxytryptamine were also determined against sepsis-induced inflammation. The present study indicated that Prop could be an efficient protector that resets sepsis-induced severe oxidative stress, inflammation and improve the immune response of the liver as well as septic neurotoxic problems.

Toxicity Effect by Binahong (Anredera cordifolia) Leaf Extract in Histopathology and Liver Weight of Guinea Pigs (Cavia cobaya)

The aim of this research was to determine the toxic effect of Anredera cordifolia leaf extract on the Cavia cobaya liver which was evaluated by the histopathological examination of liver tissue. The materials used were 8 female guinea pigs 2.5 months old that were divided into 4 groups by simple random sampling, each treatment was given to 2 female C. cobaya. Treatments given were 0, 10, 50 and 90 mg of A. cordifolia leaf extract/head, designated as T0, T1, T2 and T3, respectively. Materials were given treatment daily as long as 10 days prepartum. All of the guinea pigs were slaughtered at day 11, and the liver were taken to examined their histopathological changes. Each of the liver tissues were processed by paraffin block-embedded and hematoxylin eosin (HE) staining method. The results of this study indicate the presence of albuminosa degeneration or mild degeneration (DH +) from group control and hydropic degeneration or moderate degeneration (DH ++) in all treatment groups and the weight of C. cobaya liver which was given an extract of A. cordifolia 50 mg/head was not significantly different from the control but was significantly different from 10 and 90 mg/head. The conclusion was Binahong's (A. cordifolia) leaves extract up to the dosage 90 mg/head had no significantly toxicity effect on the liver of guinea pigs (C. cobaya).