Changes In Hepatic Tissue Research Articles

The effect of simvastatin on gene expression of low-density lipoprotein receptor, sterol regulatory element-binding proteins, stearoyl-CoA desaturase 1 mRNA in rat hepatic tissues

The study aimed to assess the effect of simvastatin on gene expression of LDLR, SREBPs, and SCD1 in rat hepatic tissues fed with high-fat diets (HFD) and its association with some biochemical parameters. Thirty-two male Wister albino rats were divided into four equal groups (three test and one control groups). The biochemical parameters were determined by using spectrophotometer techniques and the Elisa method. Low-density lipoprotein receptor, sterol regulatory element-binding proteins, stearoyl-CoA desaturase1, Beta-actin were analysed by real-time quantitative polymerase chain reaction (RT-PCR) method. At the end of study, the livers of the rats were separated and changes of hepatic tissue were determined. LDLR, SREBP2, and SCD1 expression increased significantly when compared G1 versus G4 and G2 versus G4. The expression of LDLR, SREBP2, and SCD1 also increased significantly when compared G2 versus G3, G1versus G3 and G1 versus G3 and G2 versus G3. The serum level of cholesterol, triglyceride, glucose, LDL, and HDL increased significantly when compared G1 versus G3. LDL showed significantly decreased when compared G1 versus G2. Cholesterol, glucose and HDL and triglyceride levels were increased significantly when compared G1 versus G4 and G2. Treatment of rats with HFD and simvastatin 20 mg/kg, triglyceride and LDL were almost the same as a control group and LDLR expression increased 98% in liver tissue. Gene expressions may be up-regulated in liver tissue and they showed different effects on biochemical parameters.

Clinical and laboratory associations of liver fibrosis indexes in patients with decompensated Chronic Heart Failure II-IV Functional Classes

Aim To study clinical and laboratory associations of hepatic fibrosis indexes in patients with decompensated NYHA functional class II-IV chronic heart failure (CHF).Material and methods The study included 128 patients admitted to the cardiological or therapeutic department of the University Clinical Hospital #4 at the I. M. Sechenov First Moscow State Medical University (Sechenov University) with symptoms of CHF associated with ischemic heart disease (IHD) and/or arterial hypertension (AH). All patients had signs of liver disease (liver enlargement on physical examination ± diffuse changes in hepatic tissue according to ultrasound data). Mean age was 70.59±10.71 years. Along with general clinical examination, severity of hepatic fibrosis was evaluated by calculated indexes, FIB-4, APRI, MELD-XI, and BARD. All calculations were based on laboratory data obtained within the first two days of hospitalization for decompensated CHF, at the onset of active therapy with intravenous diuretics. Statistical analyses were performed with the R programming language (3.6.1).Results In patients with NYHA FC II-IV CHF, the FIB-4 index significantly increased with the increase in NYHA FC (р<0.05). Also, the high liver density by most fibrosis indexes correlated with the probability of LV EF decrease to <40 % (FIB-4: RR, 1.32 at 95 % CI from 0.53 to 3.28, р=0.079; MELD-XI: RR, 1.62 at 95 % CI from 1.19 to 2.20, р=0.004; BARD: median LV EF, 42.5 % vs. 56 %, р=0.019), and a tendency to heart rhythm disorders was observed (FIB-4: RR, 1.92 at 95 % CI from 0.75 to 4.90, р=0.218; BARD: RR, 1.09 at 95 % CI from 0.97 to 1.22, р=0.174; MELD-XI: RR, 1.34 at 95 % CI from 0.94 to 1.90, р=0.101). Increases in liver fibrosis indexes correlated with other multiorgan disorders in CHF patients evident as a decrease in platelet count (FIB-4: р<0.01; APRI: р=0.045) and a tendency to a decrease in hemoglobin (FIB-4: 127 g/l vs. 137 g/l, p=0.249; APRI: 127 g/l vs. 136 g/l, p=0.749). Patients with a high liver density more frequently had cardiorenal syndrome diagnosed by reduced glomerular filtration rate (GFR) estimated by CKD-EPI to less than 60 ml/min / 1.73 m2 (FIB-4: р<0.03; MELD-XI: p=0.0001; BARD: р=0.005). In comparing liver fibrosis indexes in subgroups of CHF patients with preserved and reduced left ventricular ejection fraction (LV EF), significant differences were found only for MELD-XI (12.08 vs. 9.32, р=0.001).Conclusions For all studied indexes, correlations were observed with LV EF, decreases in hemoglobin, and incidence of heart rhythm disorders. For the BARD, FIB-4, and MELD-XI indexes, high results of calculations correlated with the presence of other predictors for unfavorable prognosis and disease severity (LV EF, NYHA FC, presence of type 2 diabetes mellitus, chronic kidney disease, and lower GFR). Liver fibrosis indexes are a new and promising but understudied instrument for evaluation of prognosis in CHF patients, which requires further study to determine most appropriate prognostic formulas.

Commiphora myrrha Resin Alcoholic Extract Ameliorates High Fat Diet Induced Obesity via Regulation of UCP1 and Adiponectin Proteins Expression in Rats.

This study was performed to evaluate anti-obesity potential of Commiphora myrrha resin ethanolic extract (CME) with the respect to expression of leptin, adiponectin and uncoupling protein 1 (UCP1) in rats. Control rats fed basal diet. Second group fed basal diet and administered CME (500 mg/kg bw) orally for 14 weeks. Third group fed high fat diet (HFD) for 14 weeks. Fourth group fed HFD and administered CME as second group. Fifth group fed HFD for 8 weeks then fed basal diet and administered CME as third group for another 6 weeks. Phytochemical analysis of CME identified the presence of germacrene B, 1,4-benzoquinone, benzofuran, hexadecanoic acid, 9,12-octadecnoic acid methyl ester, reynosin, 11, 14-eicosadienoic acid, isochiapin B, bisabolene epixod, elemene and 1-heptatriacotanol. High fat diet significantly increased food intake, body weight, hyperglycemia, serum levels of total cholesterol, triacylglycerol, low density lipoprotein and ketone bodies, AST and AST activities, concentration of malondialdehyde and histopathological changes in hepatic tissues. However, it significantly reduced serum levels of high density lipoprotein, leptin and adiponectin, activity of hepatic glutathione reductase (GR) and brown adipose tissue UCP1 protein expression. In contrast, CME ameliorated HFD increased body weight, hyperglycemia, dyslipidemia, ketonemia, hepatic tissues lipid peroxidation, restored hepatic tissue architecture and enhanced protein expression of leptin, adiponectin and UCP1 and activity of hepatic GR. This study indicated that CME ameliorated HFD induced hyperglycemia and dyslipidemia through normalization of HFD reduced leptin, adiponectin and UCP1 proteins production and antioxidant activity.

Exposure to arsenite and cadmium induces organotoxicity and miRNAs deregulation in male rats.

Sodium arsenite (NaAsO2) and cadmium chloride (CdCl2) are two prime examples of un-biodegradable compounds that accumulate in the ecosystems causing great threats to human health and produce severe adverse effects. However, their joint toxicities are poorly understood in mammals. This study aimed to identify the effect of exposure to NaAsO2 (5mg/kg, by oral gavage) and CdCl2 (1mg/kg injected interperitoneal, i.p.) either alone or in combinations after 14 and 28days on oxidative stress, antioxidant enzyme activities, and histopathological changes. The results revealed a downregulation of miR-146a also, in miR-let7a after 14days and a notable upregulation after 28days. However, administrations of their combinations for 14days caused downregulated miR-146a and miR-let7a. However, upregulation miR-let7a was observed only after 28days. Organotoxicity of liver results in a remarkable increase in oxidative stress biomarkers by the two metals either alone or in combinations. A remarkable decrease was noted in an antioxidant enzyme activity indicating a defect in the antioxidant defense system. Also, CdCl2 alone showed remarkable liver histopathological changes. This study concluded that there was a close relationship of high epigenetic changes as deregulation of both miR-146a and miR-let7a as a result of the joint toxicity of both compounds, and ultimately major changes in hepatic tissues that may lead to cell transformations. However, further studies are needed to investigate the target genes for those miRNAs.

Jiang Tang Xiao Ke Granule Protects Hepatic Tissue of Diabetic Mice Through Modulation of Insulin and Ras Signaling - A Bioinformatics Analysis of MicroRNAs and mRNAs Network.

ObjectiveTo investigate the impact of JTXK granule on the miRNA expression profiles in hepatic tissue of diabetic mice, and to explore the molecular targets and associated signaling pathways of JTXK granule in its anti-diabetic effect.MethodsEight mice were randomly selected as normal group fed with chow diet. Then high fat diet was used to induce diabetic model, and the mice were subsequently divided into JTXK-treated group (J group, n = 6) and model group (M group, n = 6). After 8 weeks’ intervention we examined the fasting blood glucose and observed the histopathologic changes in hepatic tissue between these two groups. Next we screened the differentially expressed miRNAs between the two groups using microRNA sequencing analysis. Finally, miRNA target gene prediction, GO and KEGG analysis were applied to explore the function of DEMs.ResultsThe blood glucose level in J group was significantly lower than M group (P < 0.05). The results from H&E staining showed that the arrangement and structure of hepatocytes from J group were basically normal with fewer ballooning degeneration and less inflammatory cell infiltration. Furthermore, a total of 33 significantly differentiated miRNAs were detected in comparison between the two groups (| log2(fold change) | >0.3, P < 0.05). MiRNA–mRNA analysis showed that mmu-miR-30a-5p, mmu-miR-23b-5p, mmu-miR-199a-5p, mmu-miR-425-5p, and mmu-miR-214-3p are closely related to inflammatory response, histological changes and insulin signal transduction in liver. In addition, KEGG analysis showed that the DEMs were closely related to Ras and insulin signaling pathway.ConclusionJTXK granule exerts anti-diabetic effect in hepatic tissue of diabetic mice by modulating miRNAs and mRNAs network.

Epigenetic and parasitological parameters are modulated in EBi3-/- mice infected with Schistosoma mansoni.

Schistosoma mansoni adaptive success is related to regulation of replication, transcription and translation inside and outside the intermediate and definitive host. We hypothesize that S. mansoni alters its epigenetic state in response to the mammalian host immune system, reprogramming gene expression and altering the number of eggs. In response, a change in the DNA methylation profile of hepatocytes could occurs, modulating the extent of hepatic granuloma. To investigate this hypothesis, we used the EBi3-/- murine (Mus musculus) model of S. mansoni infection and evaluated changes in new and maintenance DNA methylation profiles in the liver after 55 days of infection. We evaluated expression of epigenetic genes and genes linked to histone deubiquitination in male and female S. mansoni worms. Comparing TET expression with DNMT expression indicated that DNA demethylation exceeds methylation in knockout infected and uninfected mice and in wild-type infected and uninfected mice. S. mansoni infection provokes activation of demethylation in EBi3-/-I mice (knockout infected). EBi3-/-C (knockout uninfected) mice present intrinsically higher DNA methylation than WTC (control uninfected) mice. EBi3-/-I mice show decreased hepatic damage considering volume and reduced number of granulomas compared to WTI mice; the absence of IL27 and IL35 pathways decreases the Th1 response resulting in minor liver damage. S. mansoni males and females recovered from EBi3-/-I mice have reduced expression of a deubiquitinating enzyme gene, orthologs of which target histones and affect chromatin state. SmMBD and SmHDAC1 expression levels are downregulated in male and female parasites recovered from EBi3-/-, leading to epigenetic gene downregulation in S. mansoni. Changes to the immunological background thus induce epigenetic changes in hepatic tissues and alterations in S. mansoni gene expression, which attenuate liver symptoms in the acute phase of schistosomiasis.

Effect of Primidone on Liver Enzymes Levels and Hepatic Tissue Changes in Adult Male Rats

Effect of Primidone on Liver Enzymes Levels and Hepatic Tissue Changes in Adult Male Rats

Abuse of androgenic anabolic drugs with “Cycling” induces hepatic steatosis in adult male mice

BackgroundThe importance of the present study comes from the lack of sufficient information about the reversibility of the potential hepatic histopathological alterations which may result from anabolic androgenic drugs abuse by “Cycling” protocol. So, the aim of this study is to explore the negative effects of Deca-Durabolin abuse in hepatic function and structure during an administration cycle. MethodsFor our purpose, study was performed on 40 male adult mices. Animals were divided into five groups of 8 animals each treated weekly by Deca-Durabolin (nandrolone decanoate) at 30 g/kg of BW during one month (GI); during two months (GII); during three months (GIII); during three months followed by six weeks of treatment discontinuation (GIV) and Control (C). Plasma assay of liver enzymes (ALT and AST) and cytohistological examination to determine the histopathological damage properties of the liver were performed. ResultsOur results showed that the animals supported very well the administrated substance. Our study showed an increase in plasma levels of liver enzymes (ALT and AST) with the duration of treatment accompanied by important degenerative changes in hepatic tissue with peliosis evolution after two months of treatment. These damages worsen again 6 weeks after stopping treatment and ended by the development of hepatic steatosis with increases hepatic distress. ConclusionThese results ported that the use of AAS with “Cycling” may lead to the development of hepatic steatosis before progressing to more serious pathological liver situations in AAS abusers.

Polysaccharide from Phellinus igniarius alleviates oxidative stress and hepatic fibrosis in Schistosoma japonicum-infected mice

To evaluate the role of polysaccharide from Phellinus igniarius (PPI) in the improvement of oxidative stress, hepatic granuloma and hepatic fibrosis in Schistosoma japonicum-iniected in mice. The mouse model of schistosomiasis was established by S. japonicum cercariae infection via the abdomen. Balb/c mice were randomly assigned into 5 groups, including the healthy control group (Group A), infection control group (Group B), PPI treatment group (Group C), praziquantel treatment group (Group D) and PPI-praziquantel combination group (Group E), of 10 mice in each group. Each mouse in groups B, C, D and E was infected with (30 ± 2) S. japonicum cercariae. Then, mice in groups D and E were given praziquantel by gavage at a dose of 500 mg/kg for successive two days on day 42 post-infection, while mice in groups C and E were given PPI by gavage at a dose of 400 mg/kg for successive 30 days on day 42 post-infection. Histopathological changes of hepatic tissues were observed using hematoxylin-eosin (HE) staining, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) were determined, while the activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-R) and glutathione (GSH) were detected in Mouse liver homogenates. The expression of transforming growth factor-beta (TGF-β) and alpha-smooth muscle actin (α-SMA) was quantified in hepatic tissues using immunohistochemistry, and the Nrf2 and Gsta4 gene expression was quantified using quantitative real-time PCR (qPCR) assay. Untreated mice presented typical pathological changes of schistosomal hepatic disorders, while PPI treatment effectively alleviated hepatic egg granulomas and collagen deposition. S. japonicum infection resulted in aggravation of hepatic lipid peroxidation, induction of oxidative stress, elevated serum MDA level and a reduction in the activity of GSH and antioxidant enzymes activities in mice. As compared to infected but untreated mice, PPI treatment suppressed hepatic lipid peroxidation, increased the GSH activity and restored the activity of antioxidant enzymes. In addition, PPI treatment inhibited the TGF-β signaling pathway and up-regulated the Nrf2 and Gsta4 gene expression. PPI plays a critical role in the treatment of schistosomiasis-induced hepatic fibrosis. It may improve oxidative stress damages through up-regulating Nrf2 and Gsta4 gene expression, thereby suppressing the development of hepatic egg granulomas and hepatic fibrosis.

Evaluation of the ef ectiveness of alimentary correction of pathological changes in hepatic tissue under the inf uence of industrial copper-containing dust in the experiment

The results of comparative studies of the long-term ef ect (dynamics) of polymetallic dust containing 0.6% copper in the shops of Balkhash mining and metallurgical combine on the liver of rats are presented. These data on the action of dust with a predominant copper content of 0.6% give reason to assert that in the liver for 30 days there were changes in the structure, which were ref ected by metabolic rearrangements and are characterized as a failure of adaptation. The phenomena of hepatitis also took place on day 90, but these changes led to a decrease in the rate of metabolic processes. Microscopic examination showed that long-term exposure to polymetallic dust with a copper concentration of 0.6% in the body leads to signif cant changes in the liver reactive character, followed by transformation into hepatitis portal type. There is an accumulation of copper in the cytoplasm of hepatocytes; on day 90, the number of dust particles in rat hepatocytes increases by 2.25 times compared to 30 days of the experiment. T is can be explained by the inhibition of the phagocytic function of liver macrophages and ways to eliminate dust from the body. The lat er, in turn, leads to functional and metabolic damage to the structural component of the organ. It should be noted that an important role in the neutralization and removal of copper from the cell belongs to lysosomes. T ere is an assumption that copper damages lysosomal membranes and stimulates the release of enzymes from lysosomes due to a decrease in the number of mitochondria in the cell or inhibition of their enzymes. Thus, the ef ects of polymetallic dust with a copper concentration of 0.6% in the body in the early stages leads to changes in the liver, in the form of reactive hepatitis with subsequent transformation into portal-type hepatitis. The use of alimentary corrections slows down the development of post-necrotic f brosis in the liver, and there was a signif cant decrease in the volume fraction of f brotic liver tissue.

The protective role of l-carnitine against 1st- and 2nd-generation antihistamine-induced liver injury in mice

H1 antihistamines are the most widely used drugs for relieving symptoms of histamine-mediated disease. Although chlorpheniramine maleate and cetirizine hydrochloride have tolerable side effects, they induce severe side effects on chronic use such as hepatitis and cholestatic jaundice. Oxidative stress has been implicated as a mechanism of drug-induced hepatotoxicity. l-Carnitine is an effective biological active compound that is involved in oxidation of fatty acids in the liver through transportation of fatty acids into the mitochondria for energy production from fat. l-Carnitine has well-known antioxidant properties, improves hepatic function, and improves mitochondrial function in hepatic cells. In the present study, we evaluated the possible role of oxidative stress and the therapeutic and hepatoprotective effect of l-carnitine on chlorpheniramine maleate– and cetirizine hydrochloride–induced liver damage during chronic use. Methods are measurement of ALT, AST, ALP and albumin serum levels and measurement of hepatic oxidative stress biomarkers MDA and GSH in groups with and without combination with l-carnitine. Histopathological examination of changes in hepatic tissue and scoring of the induced hepatic damage was conducted in all treatment groups. Co-treatment of l-carnitine with chlorpheniramine maleate and cetirizine hydrochloride significantly improved the deteriorated hepatic function as indicated by reduction in the serum levels of ALT, AST, ALP, and elevation in serum albumin levels compared with control and untreated groups. Moreover, co-administration of l-carnitine with chlorpheniramine maleate and cetirizine hydrochloride decreased hepatic MDA and elevated hepatic GSH levels compared with control and untreated groups. Ultrastructure examination of hepatic tissue found that co-treatment with l-carnitine decreased hepatic necrosis and damage. In conclusion, oxidative stress can be a possible explanation of hepatic damage induced by chronic therapy with chlorpheniramine maleate and cetirizine hydrochloride. l-Carnitine has prominent hepatoprotective effects on chlorpheniramine maleate– and cetirizine hydrochloride–induced hepatic damage possibly through improvement of hepatic function and decreasing oxidative stress.

Sporamin suppresses growth of xenografted colorectal carcinoma in athymic BALB/c mice by inhibiting liver β-catenin and vascular endothelial growth factor expression.

BACKGROUNDColorectal cancer (CRC) is the third most common malignancy of the digestive tract and the fifth leading cause of cancer-related mortality in China. Sporamin, a Kunitz-type trypsin inhibitor isolated from sweet potato, is a potential anti-cancer agent with activities against a number of malignant tumor cells in vitro. The liver secretes a myriad of endocrine factors that may facilitate the growth and transformation of tumors in the development of CRC.AIMTo investigate the effects of sporamin on liver morphology and biomarkers of xenografted CRC in the liver of athymic BALB/c mice.METHODSTwenty-seven male BALB/c nude mice were randomly divided into control, vehicle, and sporamin groups. Mice in the latter two groups were intraperitoneally xenografted with LoVo colorectal carcinoma cells and intragastrically infused with saline or sporamin (0.5 g/kg body weight/d), respectively, for 3 wk. Hematoxylin and eosin (HE) staining of the sections was performed to observe morphological changes in hepatic tissue and real-time fluorescent quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression of β-catenin and vascular endothelial growth factor (VEGF) in the liver.RESULTSSporamin significantly reduced the number and weight of tumor nodules formed in the abdominal cavity. Compared with the vehicle group, the mean tumor weight (± SD) in the sporamin group was significantly reduced (0.44 ± 0.10 g vs 0.26 ± 0.15 g) and the total number of tumors decreased from 93 to 55. HE staining showed that enlargement of the nucleus and synthesis of proteins within hepatocytes, as well as infiltration of inflammatory cells into the liver, were attenuated by sporamin. Immunohistochemical staining and ELISA showed that the concentrations of β-catenin and VEGF in the liver were significantly reduced by sporamin. Compared with the vehicle group, the expression of β-catenin measured in integrated optical density units per area was reduced in the sporamin group (47.29 ± 9.10 vs 26.14 ± 1.72; P = 0.003). Expression of VEGF was also reduced after sporamin intervention from 20.78 ± 2.06 in the vehicle group to 15.80 ± 1.09 in the sporamin group (P = 0.021). Compared with the vehicle group, the concentration of β-catenin decreased from 134.42 ± 22.04 pg/mL to 109.07 ± 9.65 pg/mL after sporamin intervention (P = 0.00002). qPCR indicated that compared to the vehicle group, relative mRNA expression of β-catenin and VEGF in the liver of mice in the sporamin-treated group was significantly reduced to 71% ± 1% (P = 0.000001) and 23% ± 7% (P = 0.00002), respectively, of the vehicle group levels.CONCLUSIONSporamin down-regulates the expression and secretion of β-catenin and VEGF in the liver, which subsequently inhibits the transcription of downstream genes involved in cancer progression and angiogenesis.

Validation of the Use of Neorautanenia mitis (N. mitis) as an antidiarrheal therapy in Nigerian Traditional Medicine

Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined.Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24 mg/kg bw daily, po) without treatment; group 3, rats receiving 24 mg/kg bw fluoxetine, treated with 50 mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200 mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out.Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status.Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α.

LAYING PERFORMANCE, FAT DIGESTIBILITY AND LIVER CONDITION OF LAYING HENS SUPPLEMENTED WITH VITAMIN B12 OR BIOTIN AND/ OR BILE ACIDS IN DIET

For 8 weeks feeding trial, two hundred and seventy, 53 weeks old laying hens were used to investigate the effects of dietary supplementation of vitamin B12 or biotin and/or bile acids on performance, egg quality, fat digestibility and liver composition and histopathology. Birds were randomly divided into 6 groups (three replicates) and fed the experimental diets; group1 (G1) fed on the basal diet without additives as control while G2 and G3 supplemented with 0.02 ppm vitamin B12 and 0.3 mg biotin/kg diet respectively, groups 4-6 fed as the previous detailed design of G1- G3 with the addition of 400 g of dried bile acid (DBA) /tone feed. Biotin supplementation significantly (P˂0.05) increased body weight losses of laying hens, both vitamins significantly (P˂0.05) decreased daily feed intake (FI) and improved FCR. DBA addition alone or with biotin reduced these weight losses along with significant (P˂0.05) increase in daily FI. Vitamin B12 supplementation alone or with DBA increased average egg production (P˂0.05) while was reduced with biotin supplementation. Fat digestibility was non-significantly improved (P≥0.05) with both vitamins supplementation without or with DBA. Biotin significantly (P˂0.05) reduced the average yolk relative weight, which was increased when mixed with DBA, while significantly increased average egg albumin relative weight. Vitamin B12 or biotin addition without or with DBA non-significantly increased blood serum GOT and GPT activities, non-significantly reduced (P≥0.05) fat content of liver tissue (on dry matter or fresh basis) and serum lipid profile parameters except serum HDL concentration, was increased, with no histopathological changes in hepatic tissue. It could be summarized that vitamin B12 supplementation without or with DBA is recommended in layer diet as it gave the best performance, reduced serum lipid profile and improved fat digestibility and the hepatic health.Key words: layers; egg quality; liver; vitamin B12; biotin; bile acids

Protective Effects of Costunolide Against D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice.

Costunolide, a sesquiterpene isolated from Vladimiria souliei (Franch.) Ling, is known to exhibit anti-inflammatory, anti-viral, and anti-tumor activities. However, the effects of costunolide on liver injury are poorly understood. The current study aimed to investigate the hepatoprotective effects of costunolide against lipopolysaccharide (LPS) and D-galactosamine-induced acute liver injury (ALI) in mice. The results indicated that costunolide (40 mg/kg) could significantly improve the pathological changes of hepatic tissue, and reduced the LPS and D-galactosamine-induced increases of alanine aminotransferase (from 887.24 ± 21.72 to 121.67 ± 6.56 IU/L) and aspartate aminotransferase (from 891.01 ± 45.24 to 199.94 ± 11.53 IU/L) activities in serum. Further research indicated that costunolide significantly reduced malondialdehyde content (from 24.56 ± 1.39 to 9.17 ± 0.25 nmol/ml) and reactive oxygen species (from 203.34 ± 7.68 to 144.23 ± 7.12%), increased the activity of anti-oxidant enzymes superoxide dismutase (from 153.74 ± 10.33 to 262.27 ± 8.39 U/ml), catalase (from 6.12 ± 0.30 to 12.44 ± 0.57 U/ml), and total anti-oxidant capacity (from 0.64 ± 0.06 to 6.29 ± 0.11 U/ml) in hepatic tissues. Western blot results revealed that costunolide may trigger the anti-oxidative defense system by inhibiting kelch-like ECH-associated protein 1 and nuclear factor-related factor 2 (cytosol), increasing nuclear factor-related factor 2 (nucleus), heme oxygenase-1 and NAD (P) H quinone oxidoreductase 1 activity. Moreover, costunolide significantly decreased the protein expression of proinflammatory cytokines including interleukin 1β, interleukin 6, and tumor necrosis factor. Pretreatment with costunolide could reduce the expression of toll-like receptor 4, myeloid differentiation factor 88, p65 (Nucleus), phosphorylated IκB kinase α/β, inhibitor of nuclear factor kappa-B kinase, inhibitor kappa Bα and prevent the expression of phosphorylated inhibitor kappa B kinase which repressed translocation of p65 from cytoplasm to nucleus. In addition, pretreatment with costunolide also inhibited hepatocyte apoptosis by reducing the expression of B-cell lymphoma 2 associated X, cytochrome C, cysteinyl aspartate specific proteinase 3, cysteinyl aspartate specific proteinase 8 and cysteinyl aspartate specific proteinase 9, and by increasing B-cell lymphoma 2. From the above analysis, the protective effects of costunolide against LPS and D-galactosamine-induced ALI in mice may be attributed to its anti-oxidative activity in nuclear factor-related factor 2 signaling pathways, anti-inflammatory suppression in nuclear factor-kappa B signaling pathways, and inhibition of hepatocyte apoptosis. Thus, costunolide may be a potential therapeutic agent in attenuating LPS and D-galactosamine -induced ALI in the future.

Protective effects of Liuweiwuling tablets on carbon tetrachloride-induced hepatic fibrosis in rats

BackgroundLiuweiwuling tablets (LWWL) are an herbal product that exerts remarkable effects on liver protection and aminotransferase levels, and they have been approved by the Chinese State Food and Drug Administration (CFDA). Clinical studies have found that LWWL can inhibit collagen production and reduce the levels of liver fibrosis markers in the serum. Thus, LWWL is expected to have beneficial effects in the treatment of liver fibrosis. The purpose of this study was to evaluate the pharmacological effects of LWWL.MethodsHepatic fibrosis was induced in rats via carbon tetrachloride (CCl4) treatment. The rats were treated twice weekly for 8 weeks with either 2 mL·kg− 1 body weight of a 50% solution of CCl4 in olive oil or olive oil alone by oral gavage. A subset of rats received daily intraperitoneal injections of either colchicine (0.2 mg/kg per day), LWWL (0.4, 1.6, or 6.4 g/kg per day), or vehicle (N = 12 for all groups) during weeks 9–12. The rats were sacrificed after 12 weeks. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and Sirius Red staining. Immunohistochemistry was performed to observe α-smooth muscle actin (α-SMA) and collagen type I (collagen I) protein expression. Western blotting was also used to detect α-SMA protein expression. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect transforming growth factor-1 (TGF-β1), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinase-1 (TIMP1), and tissue inhibitor of metalloproteinase-2 (TIMP2) mRNA expression.ResultsLWWL significantly reversed histological fibrosis and liver injury, reduced the hydroxyproline content in liver tissue, and decreased α-SMA and collagen I expression. LWWL also suppressed hepatic stellate cell (HSC) activation by reducing the expression of the profibrogenic factors TGF-β1 and PDGF. The expression levels of TIMP1 and TIMP2, which regulate extracellular matrix (ECM) degradation, were decreased after CCl4 injury in LWWL-treated rats.ConclusionsThese data suggest that LWWL may serve as a promising therapeutic agent to reduce fibrogenesis.

Apple Cider Vinegar (as a Prophetic Medicine Remedy) Exerts Tissue-protective Effects in Streptozotocin-induced Diabetes in Animals

Background: Diabetes mellitus (DM) was reported to be related to occurrence of both biochemical and histopathological changes in hepatic tissue. DM-induced tissue damage and decreased immunity may favor carcinogenesis and tumor development in pediatric practice and adults. In this study, we aimed at investigating the hepatoprotective and tissue-protective effects of apple cider (ACV) against DM-induced hepatic derangements over a relatively long period (30 days). Effects were evaluated using streptozotocin (STZ)-induced DM in rats as an experimental model. Materials and methods: DM was experimentally caused by injecting one dose of STZ (65 mg/kg given through intraperitoneal injection. Thirty wistar rats were categorized into three experimental groups: control group, STZ-treated group and STZ plus ACV treated group 2 ml/kg BW). Animals were sacrificed 30 days post treatment. Results: Our study revealed that ACV administration induced hepatoprotective effects in diabetic rats. Biochemically, ACV reduced significantly serum glycemic values (glucose, total cholesterol, low density lipoprotein-cholesterol while high density lipoprotein cholesterol significantly increased). STZ-induced DM in rats was associated with marked fatty changes hepatocytes cytoplasm evidenced by accumulation of lipid droplets and inflammatory changes e.g. lymphocytic infiltration. That was confirmed by Electron microscopic evaluation that showed aggregations of polymorphic mitochondria, loss of mitochondrial cristae and condensed mitochondrial matrices. Hepatocytes cytoplasm showed vacuolations with a large number of variable-sized lipid droplets. Hepatocytes rough endoplasmic reticulum got distorted and fragmented into smaller stacks. ACV proved effective in reversing all these metabolic changes. ACV-treated hepatocytes exhibited minimal STZ-induced toxic effects. ACV enhanced recovery of the injured hepatocytes and normalized serum biochemical values. In prophetic medicine, Prophet Muhammad (Allah's apostle peace be upon him) strongly advised eating and considered it as the best edible as narrated in the prophetic hadith: vinegar is the best edible. Conclusion: ACV is promising as a food additive or as a part of diet in diabetic patients particularly in early stages of DM. ACV slows down DM progress and causes hepatoprotection against the metabolic damages resulting from STZ- induced diabetes mellitus

Effects of corilagin on alleviating cholestasis via farnesoid X receptor-associated pathways in vitro and in vivo.

The aim of this study was to investigate the ameliorative effects of corilagin on intrahepatic cholestasis induced by regulating liver farnesoid X receptor (FXR)-associated pathways in vitro and in vivo. Cellular and animal models were treated with different concentrations of corilagin. In the cellular experiments, FXR expression was up-regulated by either lentiviral transduction or GW4064 treatment and down-regulated by either siRNA technology or treatment with guggulsterones. Real-time PCR and Western blotting were employed to detect the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, CYP7A1, CYP7B1, NTCP, MRP2 and SULT2A1. Immunohistochemistry was used to examine the expression of BSEP in liver tissues. Rat liver function and pathological changes in hepatic tissue were assessed using biochemical tests and haematoxylin and eosin staining. Corilagin increased the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, MRP2 and SULT2A1, and decreased those of CYP7A1, CYP7B1 and NTCP. After either up- or down-regulating FXR using different methods, corilagin could still increase the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, MRP2 and SULT2A1 and decrease the protein levels of CYP7A1, CYP7B1 and NTCP, especially when administered at a high concentration. Corilagin also exerted a notable effect on the pathological manifestations of intrahepatic cholestasis, BSEP staining in liver tissues and liver function. Corilagin exerts a protective effect in hepatocytes and can prevent the deleterious activities of intrahepatic cholestasis by stimulating FXR-associated pathways.

Effect of Exercise Training on Metabolic Homeostasis and Some Hemodynamics (Some Hepatic and Cardiovascular Functions) in Experimentally Induced Obesity

Background: Obesity is associated with many chronic disorders such as type-2 diabetes mellitus, essential hypertension and non-alcoholic fatty liver disease (NAFLD). High fat diet (HFD) induced obesity in rats is associated with altered adipocytes release of several adipocytokines. Physical exercise has also been shown to have positive effects in the prevention and attenuation of many of the obesity-related disorders, however; the mechanisms have not been fully elucidated. Objective: The present study was designed to examine the effect of moderate intensity exercise training on existing cardio metabolic and hepatic complications linked to obesity including dyslipidemia, insulin resistance, hypertension and NAFLD. Materials and methods: Thirty healthy adult male albino rats of initial body weight 151-190 gm were included. Rats were randomly and equally divided into 3 groups: group (1): normal diet fed group, group (II): HFD induced obesity group in which obesity was induced by HFD for 12 weeks and group (III): HFD induced obesity group fed on high fat diet for 12 weeks then followed by moderate intensity swimming exercise training for 8 weeks. Rats were examined for the body weight, length, abdominal circumference (AC) and body mass index (BMI), Systolic, diastolic & mean arterial blood pressures, heart rate, serum glucose, insulin & HOMA-IR, serum total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) & atherogenic index (AI), serum adiponectin, leptin, irisin, , tumor necrosis factor alpha (TNF- α), Interleukin-6 (IL-6) malondialdehyde (MDA), superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline Phosphatase (ALP), lactate dehydrogenase (LDH) and albumin. Histopathological examination for hepatic tissue was also evaluated. Results: The present study revealed that HFD significantly increased final body weight, BMI, AC, Systolic, diastolic & mean arterial blood pressures, heart rate, serum levels of glucose, insulin, TC, TG, LDL, VLDL, ALT, AST, ALP, LDH, TNF- α, IL-6, MDA and leptin levels, in addition to HOMA-IR and atherogenic index in HFD-induced obesity group. However, there were significant decreases in serum levels of HDL, SOD, albumin, adiponectin and irisin levels in the same group. Histopathological changes in hepatic tissue that indicate the development of NASH were also observed in HFD-induced obesity group. On the other hand, chronic moderate intensity swimming exercise training significantly reversed all these manifestations even in the absence of caloric restriction. Conclusion: moderate exercise training seems to be an effective strategy to reverse almost all risk factors of cardiovascular diseases and NAFLD associated with metabolic syndrome.

Intervention effects of Dan-fang capsule in rats with hepatic fibrosis

Objective: To investigate the interventional effect of Dan-fang capsule on liver fibrosis in rats. Methods: Sixty one-week aged male healthy SD rats [weight (180±20) g] were randomly divided into normal control group (group A), hepatic fibrosis model group (group B), Fu-Fang-Bie-Jia-Ruan-Gan tablet group (group C), Dan-fang capsule groups at high, middle and low dose group (group D, E, F, respectively). Except for the normal control group, hepatic fibrosis was induced in other groups by intraperitoneal injection of porcine serum.Simultaneously, rats in Dan-fang capsule groups were administered by gavage with Dan-fang capsule at doses of 4.32, 2.16, 0.54 g/kg, respectively.Rats in Fu-Fang-Bie-Jia-Ruan-Gan tablet group were orally administered by gavage with Fu-Fang-Bie-Jia-Ruan-Gan tablet (0.54 g/kg) every day and the normal control group received saline alone.All rats were killed at the end of the 12th week. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and PⅢnp clia (PⅢNP) were measured in the groups.Pathology changes of hepatic tissue were evaluated by hematoxylin-eosin (HE) and Masson staining.The proteinic expressions of alpha-smooth muscle actin (α-SMA), collagen-Ⅰ (COL-Ⅰ) and collagen-Ⅲ (COL-Ⅲ) were observed with the method of immunohistochemistry.Analysis of variance was applied when data were compared among groups. Results: Compared with those in the group A, the levels of ALT, AST and PⅢNP in serum and the expressions of α-SMA, COL-Ⅰ and COL-Ⅲ in liver tissues were significantly higher in group B [(68.3±3.4) vs (51.5±6.3) U/L, (205±52) vs (135±24) U/L, (3.1±1.4) vs (1.6±0.6) μg/L and 0.35±0.02 vs 0.13±0.02, 0.37±0.02 vs 0.13±0.02, 0.43±0.13 vs 0.13±0.01, t=17.020, 71.053, 1.552, 0.214, 0.241, 0.292, all P<0.01], and the degree of liver fibrosis significantly increased in group B than that in group A. Compared with those in group B, the levels of ALT, AST, PⅢNP and the expressions of α-SMA, COL-Ⅰ, COL-Ⅲ were all significantly lower in group D, E and F (t=-58.232--0.104, all P<0.01). The degree of liver fibrosis significantly reduced in group D, E and F than that in group B (Z=3.82, 3.76, 3.90, all P<0.05). Conclusion: Dan-fang capsule has certain preventive effect on liver fibrosis that caused by porcine serum in rats.